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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Frailty is a state of increased vulnerability to physical stressors like illness which leads to poor clinical outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">1</span></a> It is a condition usually found in elderly people and occurs as a result of progressive and sustained degeneration in multiple physiological systems in our body&#46; This is further worsened because of a decline in psychological health and inadequate social support&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">1&#8211;3</span></a> The prevalence of frailty is around 11&#37; in elderly without end stage renal disease &#40;ESRD&#41;&#44; whereas in patients with ESRD on dialysis it is more than 60&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">4&#44;5</span></a> It is characterized by weakness&#44; balance and motility issues&#44; and a decreased ability to resist stressors&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">6&#44;7</span></a> Impaired physical function&#44; sarcopenia&#44; and an increased risk of falls are hallmarks of the frailty syndrome&#46; Other adverse health outcomes include fractures&#44; hospitalization&#44; institutionalization&#44; disability&#44; dependence&#44; dementia&#44; poor quality of life&#44; and death&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">8</span></a> Frailty in chronic kidney disease &#40;CKD&#41; has been described as &#8220;senescent nephropathy&#8221; &#8211; a state characterized by a synergistic decline in physical and renal function&#44; proposed to be caused by increased levels of inflammation associated with each condition&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">6</span></a> Inspite of being an important prognostic marker&#44; frailty screening is yet to be widely implemented in routine renal care&#46; Patients with CKD&#44; especially ESRD are at a high risk of being frail&#46; Though there are many frailty measuring tools available&#44; the optimal means of screening for frailty in patients with kidney disease remains perplexing&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathogenesis of frailty in ESRD is multifactorial and is different from the general population since uraemia and dialysis are significant contributors&#46; Additionally&#44; standard management of ESRD&#44; including kidney replacement therapies&#44; may have a lower benefit or may be even potentially harmful in the presence of frailty&#46; Recently&#44; several interventions to modify frailty in ESRD have been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">9</span></a> In this review&#44; we highlight the importance of frailty screening in ESRD&#44; different tools for its measurement and its pathogenesis&#46; We also recapitulate the available evidence on frailty as a predictor of poor clinical outcomes&#44; as well as current guidelines for its management&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definitions and frailty measurement tools</span><p id="par0015" class="elsevierStylePara elsevierViewall">Frailty has been defined as a state of increased vulnerability to stressors like illness or trauma due to degeneration in multiple systems in our body leading to poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">1</span></a> Recently efforts have been put to create an operational definition for frailty&#44; so that it aids in its identification and severity&#46; In literature&#44; two principal concepts are described&#58; the Fried Phenotype Model of Frailty&#44; which focuses frailty as a physical phenotype characterized by sarcopenia&#44; and the other more holistic Frailty index &#40;Cumulative Deficit Model of Frailty&#41; which additionally incorporates other domains like comorbidities and psychological conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">10&#8211;14</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Frailty Phenotype &#40;FP&#41; is described as &#8216;a clinical syndrome involving at least three of the following&#58; unintentional weight loss&#44; self-reported exhaustion&#44; weakness&#44; slow walking speed and low physical activity&#8217;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; The presence of one or two of the above characteristics defines a patient as pre-frail&#46; In FP&#44; the measures of weakness and walking speed examination is cumbersome and time consuming&#46; So the FP has been modified in an attempt to reduce the burden of data collection by several studies on CKD populations which have used modified versions of the FP&#44; where questionnaire-based assessments for the objective measures of weakness and slowness are used&#46; Though these methods may overestimate the prevalence of frailty&#44; they also predict outcomes similar to FP&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">15&#8211;18</span></a> A study demonstrated that modified FP was independently associated with increased mortality risk in dialysis-dependent CKD &#91;HR 2&#46;24 &#40;95&#37; CI 1&#46;60&#8211;3&#46;15&#41;&#93; and also with an increased risk of the combined endpoint of hospitalization or death &#91;HR 1&#46;56 &#40;95&#37; CI 1&#46;36&#8211;1&#46;79&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">16</span></a> Similar to the FP&#44; the short physical performance battery &#40;SPPB&#41; is comprised of three physical assessments&#58; standing balance&#44; gait speed&#44; and a chair stand test&#46; Like the FP&#44; its strengths also lie in its objectivity&#46; In addition&#44; it provides a range of scores&#44; from 0 &#40;worst performance&#41; to 12 &#40;best performance&#41;&#44; allowing some quantification of a patient&#39;s level of frailty&#46; Importantly&#44; in patients with CKD&#44; the SPPB is reliable&#44; <a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">19</span></a> associated with disease progression and is predictive of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">20</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">A contrasting and holistic approach to the Cumulative Deficit Model of Frailty was described in the older population&#46; <a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">11</span></a> A remodification of this model included a total of 70 variables consisting of a variety of medical&#44; psychological and functional impairments&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> This led to the creation of a more global and complete frailty assessment&#44; the frailty index &#40;FI&#41;&#46; FI score was calculated by dividing the total number of deficits for an individual patient by all the predetermined clinical variables&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">3</span></a> A study compared FI with FP in elderly individuals and demonstrated that these operational definitions of frailty correlated moderately well with each other&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">12</span></a> They categorized participants as robust&#44; pre-frail &#40;intermediate frailty&#41; and frail as per FP&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">12</span></a> FI and FP were found to be comparable in frailty assessment in CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">21</span></a> But the FI is demanding to implement into routine clinical care&#44; as at least 30 variables are required to calculate the score making it a relatively time-consuming alternative&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">22&#44;23</span></a> However&#44; with the advent of electronic health records&#44; it may be possible to surpass this challenge&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The Groningen frailty indicator &#40;GFI&#41; is another multidimensional method of assessing frailty&#46; It consists of 15 questions across 8 domains&#44; including mobility&#44; vision&#44; hearing&#44; nutrition&#44; comorbidity&#44; cognition&#44; psychosocial&#44; and physical fitness&#46; The absence of physical testing and a better assessment of psychosocial status makes its afavoured screening test&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a> GFI was equally predictive of death and hospitalization in CKD population as other approaches&#44; but it failed to distinguish specific deficits&#44; especially of a physical nature&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">25</span></a> This could be due to the reason that physical impairment is screened with a single question&#44; asking the patient to rate their fitness from 0 to 10&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The multidimensional prognostic index &#40;MPI&#41; has been developed to predict the longevity of hospitalized adults&#46; In MPI&#44; frailty status is assessed through eight individual assessments including function &#40;activities of daily living&#41;&#44; polypharmacy&#44; mental status&#44; nutrition&#44; comorbidity&#44; risk of pressure sores and social circumstances&#46; Deficits in each domain are graded as 0 &#40;none&#41;&#44; 0&#46;5 &#40;minor&#41;&#44; or 1 &#40;major&#41;&#44; and then averaged&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">26</span></a> A score greater than 0&#46;66 is indicative of frailty and associated with increased hospital mortality and length of stay in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">27</span></a> In the elderly CKD population&#44; the addition of the MPI to the estimated GFR drastically improved prediction of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">28</span></a> A study revealed that maintenance haemodialysis &#40;HD&#41; patients had higher MPI scores than the global geriatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">29</span></a> The limitation of the MPI score is that it is only been validated in admitted CKD patients and needs endorsement before generalization to the outpatient CKD population&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally&#44; to produce a simple yet global frailty assessment for screening purposes&#44; a clinical frailty scale &#40;CFS&#41; has been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> Simplicity is the hallmark of the CFS when compared to other methods of assessing frailty&#46; CFS relies on clinical judgement alone and higher scores on the CFS were associated with an increased risk of death &#91;HR 1&#46;30 &#40;95&#37; CI 1&#46;27&#8211;1&#46;33&#41;&#93; and hospitalization &#91;HR 1&#46;46 &#40;95&#37; CI 1&#46;39&#8211;1&#46;53&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> In its original form&#44; the CFS was a 7-point scale<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> and later updated to include nine descriptors&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">23</span></a> The CFS has been shown to have similar predictive characteristics as the FP and FI in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">12&#44;13</span></a> In addition&#44; like the SPPB and FI&#44; the CFS is graduated and allows for monitoring of changes in frailty severity over time&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">30</span></a> CFS scores at dialysis initiation are associated with higher mortality<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">31</span></a> and worse health-related quality of life scores in older patients on assisted peritoneal dialysis &#40;PD&#41; and HD&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">32</span></a> CFS seemingly agreed with the FP better than the SPPB and FI&#44; suggesting that the CFS may be a valuable option for accurate screening of frailty when it is not practical to perform a physical assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">33</span></a> So CFS is a promising frailty screening tool that could be incorporated into routine clinical renal care&#46; The limitations of the CFS are being a subjective tool and yet to have robust validation data in CKD&#46; Currently there is no consensus as to which measurement of frailty is superior&#46; Since all approaches are associated with clinical outcomes&#44; it is more important that efforts are made to identify frailty in ESRD&#44; regardless of the adopted methodology&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathogenesis of frailty in ESRD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">The pathogenesis of frailty in ESRD is multifactorial&#46; Reduced intake contributes to sarcopenia and later physical frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">35</span></a> The contributing factors for loss of appetite include the uraemic milieu&#44; inflammation&#44; comorbid illnesses&#44; medications and associated low mood and cognitive impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;36</span></a> Physical inactivity is the other important factor in CKD which contributes for sarcopenia&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">37</span></a> The increased levels of pro-inflammatory cytokines like interleukin &#40;IL-6&#41; and tumour necrosis factor alpha &#40;TNF-a&#41;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">38</span></a> leads to impaired signalling of the anabolic hormones insulin and insulin-like growth factor-1 &#40;IGF&#41;-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;39</span></a> This leads to muscle protein breakdown via the caspase-3 and ubiquitin proteasome system&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">38</span></a> Metabolic acidosis also activates caspase-3 and inhibits intracellular signalling of insulin and IGF-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;38</span></a> All of the above results in a state of protein catabolism leading to sarcopenia&#46; It has been shown that 1&#44; 25&#40;OH&#41;<span class="elsevierStyleInf">2</span> D is a determinant of physical function and muscle size in those with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">40</span></a> So deficiency of Vitamin D also may be a factor in the development of frailty in CKD&#46; Finally&#44; cellular senescence&#44; loss of telomeric structures&#44; mitochondrial dysfunction&#44; increased free radical production and poor DNA repair capability are important in the ageing process and the development of frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">41</span></a> These processes occur prematurely in CKD population ultimately leading to sarcopenia&#44; vascular dysfunction and progressive organ damage&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">42</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Frailty as a marker of prognosis in ESRD</span><p id="par0050" class="elsevierStylePara elsevierViewall">Fraility is independently predictive of adverse outcomes&#44; including falls&#44; hospitalization and mortality in the elderly general population&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> Furthermore&#44; the presence of intermediate frailty &#40;or pre-frailty&#41;&#44; was predictive of becoming frail over the next 3&#8211;4 years&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> Studies that were done in the ESRD patients also show a similar pattern&#46; A study demonstrated that frailty at dialysis initiation was associated with an increased risk of mortality &#91;hazard ratio &#91;HR&#93; 1&#46;57 &#40;95&#37; CI 1&#46;25&#8211;1&#46;97&#41;&#93; and first hospitalization &#91;HR 1&#46;26 &#40;95&#37; CI 1&#46;09&#8211;1&#46;45&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">5</span></a> Another study categorized dialysis patients as either non-frail&#44; intermediately frail or frail&#46; It was seen that proportion of participants admitted to hospital on two or more occasions over the subsequent year after enrolment was 43&#37; for frail dialysis patients compared to 28&#37; for nonfrail dialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a> The 3-year mortality was 40&#37; for frail dialysis patients&#46; 34&#37; of those categorized as intermediately frail patients died within the 3-year follow-up period&#44; compared with only 16&#37; of those who are non-frail&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a> Thus&#44; differentiating degrees of frailty offers even greater clinical utility&#46; Another study by the same group assessed frailty in 95 dialysis patients for falls&#46; Over a 6&#46;7-month follow-up period&#44; there were 3&#46;09-fold &#40;95&#37; CI 1&#46;38&#8211;6&#46;90&#41; more falls in frail patients&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">44</span></a> The other studies in dialysis patients are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; With the present evidence&#44; it is clear that assessment of frailty is an important prognostic indicator in dialysis patients and it predicts mortality&#44; hospitalization and falls irrespective of the methods used for assessment&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Current guidance</span><p id="par0055" class="elsevierStylePara elsevierViewall">Among present guidelines on dialysis&#44; the frailty is being addressed in the 2016 European renal best practice &#40;ERBP&#41; guideline&#46; Frailty screening should be considered in all older adults who are not otherwise at risk of imminently dying or at low risk for progression to ESRD&#46; It emphasizes that frailty scores may help in providing additional information during assessment and shared decision-making on the planning of patients&#46; No specific screening test was recommended&#46; It suggested that after an initial assessment&#44; functional status be reassessed every 6&#8211;8 weeks for dialysis patients&#46; It also recommends exercise therapy and dietary interventions as potential means of modifying frailty and frailty assessment to be a part of advanced care planning &#40;ACP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a> In 2015&#44; Kidney Disease&#58; Improving Global Outcomes &#40;KDIGO&#41; in partnership with the International Society of Nephrology &#40;ISN&#41;&#44; hosted a controversies conference on supportive care in CKD&#46; The conference highlighted the need for identifying patients pre-dialysis and as well on dialysis who may be frail and may not benefit or may worsen with continuation of dialysis&#46; There was no consensus on ideal tools to decide on patients requiring conservative care&#46; However&#44; there was a stress on using appropriate tools like the modified Karnofsky activity scale or screening activities of daily living&#44; use of &#8220;surprise question&#8221; to assess and prognosticate the patients for conservative care versus conventional kidney replacement therapy &#40;KRT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">52</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Management</span><p id="par0060" class="elsevierStylePara elsevierViewall">Frail patients with CKD are a distinct population&#44; their risk profile will be different from fit patients&#46; Although&#44; frailty most commonly follows a downward trajectory&#44; there is growing evidence to suggest that it can be improved with intervention&#46; A holistic assessment with individualized assessment and targeted management strategy will be the key&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">First and foremost&#44; it is important to address undernutrition&#46; The possible causes for decreased appetite&#44; like uraemia&#44; metabolic acidosis&#44; intercurrent illness&#44; medications&#44; and comorbid conditions such as depression should be identified and treated&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;39&#44;53</span></a> Though there might not be a survival benefit &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#41;&#44; but oral nutritional supplementation was associated with fewer hospital admissions&#44; in those with ESRD and hypalbuminaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">54</span></a> The dietary phosphate restriction in ESRD patients with frailty may outweigh the benefits and result in further worsening of undernutrition and protein-energy&#46; So dietary phosphate restriction should be individualized to allow adequate nutritional intake&#46; Recent guidelines by ERBP in 2016 state that &#8216;preserving nutritional status should prevail over any other dietary restriction&#8217;&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Exercise has well-established&#44; multifaceted benefits for improving the frailty in ESRD patients&#46; Dialysis patients&#44; in general&#44; live a sedentary lifestyle&#46; Decreased physical activity in elderly haemodialysis patients has been associated with a risk of increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">55</span></a> Exercise helps in improvements in muscle strength&#44; cardiovascular function&#44; physical function and health-related quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">56</span></a> Even a modest amount of exercise in severely frail patients have shown a variety of benefits like better mobility&#44; independence&#44; quality of life&#44; bone mineral density and reduced falls&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">57</span></a> Aerobic&#44; resistance and combined exercise programmes have demonstrated substantial benefits&#46; Both intradialytic and interdialytic exercise programmes are helpful in improving frailty&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">58&#8211;60</span></a> Regular exercise increased muscle mass and reduced systemic inflammation in CKD population&#46;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">61&#44;62</span></a> A study concluded that exercising during non-dialysis days was most effective&#44; but intra-dialysis exercising was both effective and preferable&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">59</span></a> Individualized exercise programme should be part of targeted therapy for all frail ESRD patients and seems to be valuable regardless of the type or mode of exercise&#46; Apart from nutritional care and exercise&#44; falls prevention measures&#44; and timely control of ESRD complications&#44; the inclusion of frailty management as part of ACP may help frail ESRD patients to improve their overall outcomes&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Choice of KRT in frail ESRD</span><p id="par0075" class="elsevierStylePara elsevierViewall">Dialysis and transplant are significant stressors to an ESRD patient&#44; and therefore should only be expected to benefit who are adequately robust&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">63</span></a> The severity of frailty significantly impacts on patient&#39;s experience of different kidney replacement therapies&#46; As a patient&#39;s frailty severity progresses&#44; the nephrologist&#39;s focus should shift to potentially modifying care to less invasive treatment options like incremental dialysis or conservative management&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Incremental HD is one of the proposed strategies for limiting frailty&#46; It has been shown to slow the loss of residual kidney function in ESRD&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">64</span></a> It means to start with one&#47;week or two&#47;week HD regimens which are shorter or less frequent than standard three times per week maintenance therapy&#46; Later it can be increased over time to accommodate a further decline in residual kidney function&#46; By starting frail patients on incremental HD&#44; the physiologic stress of dialysis is decreased&#46; It leads to reduced post dialysis recovery time&#44; less interference with social and family life&#44; and ultimately better quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">65</span></a> Incremental PD may be considered as an option as well&#46; Home HD &#40;either conventional&#44; frequent&#44; or intensive&#41; in frail patients may be another solution&#46; But the evidence on peritoneal or home HD is not substantial&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">32&#44;66</span></a> Similar to PD&#44; home HD allows greater involvement of family&#44; no travel burden of in-centre haemodialysis&#44; and more flexibility&#46; An important future consideration is an evaluation of the impact of PD or home HD on frailty&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Kidney transplant is a significant physiologic stress to frail ESRD patients&#46; Frail patients have an increased risk of postoperative complications and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">67&#44;68</span></a> It is currently unclear at what degree of frailty the risks of transplantation outweigh the benefits&#46; But transplant itself may be one of the &#8220;interventions&#8221; that could improve a patient&#39;s frailty significantly&#46; Although frailty initially worsens post-transplant&#44; it has been shown to improve as early as three months post transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">69</span></a> A study showed a similar survival benefit in frail and fit patients by 9 months post-transplant&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">70</span></a> As frailty advances&#44; the risks and benefits of more invasive options for KRT should be reassessed&#46; The option of conservative treatment with symptomatic management without any dialytic support must be explored with patients and families&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Frailty is highly prevalent in ESRD patients independent of age&#46; The pathogenesis of frailty in ESRD is multifactorial&#46; Frail patients are likely to have higher morbidity and mortality compared to non-frail counterparts&#46; Many frailty screening tools have been studied and validated in different settings of CKD and ESRD&#46; In the absence of a consensus on the ideal screening tool&#44; the emphasis should be placed on to use any one of the tools to identify frailty&#46; A holistic individual assessment to address risk factors that may exacerbate its progression should be considered&#46; Adequate nutritional intake is essential and individualized exercise programmes should be offered to all frail ESRD patients along with psychological and social support&#46; Though the ERBP in 2016 and KDIGO in 2015 have attempted to incorporate frailty screening in ESRD population&#44; it is yet to receive widespread acceptance&#46; It is the time for the nephrology community to include it in routine practice to inform discussions with patients about conservative treatment or select a suitable mode of kidney replacement therapy&#44; tailor the dialysis prescription as per the needs of the individual rather have a &#8220;one size fits all&#8221; approach&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Data availability</span><p id="par0095" class="elsevierStylePara elsevierViewall">Not required&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethical approval</span><p id="par0100" class="elsevierStylePara elsevierViewall">The procedures followed were in accordance with Declaration of Helsinki and its revisions&#46; Informed consent from the subjects is not required</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">Not required&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Definitions and frailty measurement tools"
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          "titulo" => "Pathogenesis of frailty in ESRD &#40;Fig&#46; 1&#41;"
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          "titulo" => "Frailty as a marker of prognosis in ESRD"
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            1 => "End stage renal disease"
            2 => "Dialysis"
            3 => "Sarcopenia"
            4 => "Senescent nephropathy"
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            0 => "Fragilidad"
            1 => "Enfermedad renal en etapa terminal"
            2 => "Di&#225;lisis"
            3 => "Sarcopenia"
            4 => "Nefropat&#237;a senescente"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Frailty is common in end stage renal disease &#40;ESRD&#41; and is a marker of poor outcomes&#46; Its prevalence increases as chronic kidney disease &#40;CKD&#41; progresses&#46; There are different measurement tools available to assess frailty in ESRD&#46; The pathogenesis of frailty in ESRD is multifactorial including uraemia and dialysis related factors&#46; In this current review&#44; we discuss the importance of frailty&#44; its pathogenesis&#44; screening methods&#44; prognostic implications and management strategies in context of ESRD&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La fragilidad es com&#250;n en la enfermedad renal en etapa terminal &#40;ESRD&#41; y es un marcador de malos resultados&#46; Su la prevalencia aumenta a medida que avanza la enfermedad renal cr&#243;nica &#40;ERC&#41;&#46; Hay diferentes herramientas de medici&#243;n disponibles para evaluar la fragilidad en la ERT&#46; La patogenia de la fragilidad en la ESRD es multifactorial que incluye uremia y factores relacionados con la di&#225;lisis&#46; En esta revisi&#243;n actual&#44; discutimos la importancia de la fragilidad&#44; su patog&#233;nesis&#44; m&#233;todos de cribado&#44; implicaciones pron&#243;sticas y estrategias de manejo en el contexto de la ESRD&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Ankur Gupta act as guarantor for other authors&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pathogenesis of frailty in end stage renal disease &#40;Abbreviations&#58; CNS &#8211; central nervous system&#44; CKD &#8211; chronic kidney disease&#44; MIA &#8211; malnutrition inflammation-atherosclerosis&#44; IGF &#8211; insulin like growth factor&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disadvantages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried&#39;s frailty criteria &#40;Fried et al&#46;&#44; 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physical &#8211; weight loss&#44; low physical activity&#44; exhaustion&#44; slowness&#44; weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Most commonly used and extensively validated in chronic kidney disease &#40;CKD&#41; and end stage renal disease &#40;ESRD&#41; populationObjective measures also used hence reproducible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Need to perform physical testsAssesses only physical domainCategorical grading of components&#44; hence may identify only moderate to severe casesWeight loss criteria may not be practical in dialysis patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Short Physical Battery performance &#40;Guralnik et al&#46;&#44; 1994&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physical &#8211; Balance&#44; gait&#44; strength&#44; and endurance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Validated in CKD and ESRD populationObjective assessmentRisk scoring is on a continuous scale hence can help identify mild cases and also monitor progress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Only physical domains assessedPhysical testing may be cumbersome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Groningen Frailty Indicator &#40;Steverink et al&#46;&#44; 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical&#44; cognitive&#44; social and psychological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No physical tests to be performed hence easierGives information of day to day functionality of the patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not well validated in CKD and ESRDSubjective assessment in many domainsLess sensitive to detect defects in physical domains&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Frailty Scale &#40;Rockwood et al&#46;&#44; 2005&#41;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical cognitive&#44; functional&#44; comorbid illness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Based on clinical judgement&#44; simple to useAllows for gradation and monitoring progress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Many components subjectiveVery fit ESRD patients will also be scored as 3 &#40;Managing Well&#41; on account of co-morbidityNot well validated CKD&#47;ESRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty Index &#40;Rockwood and Mitnitsky 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical&#44; cognition&#44; co morbid illness&#44; symptoms&#44; disabilities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Covers multiple domains&#44; which can be created specifically for a target populationPatients can be graded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time consuming to calculate because of mathematical nature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multidisciplinary prognostic index &#40;Pilotto et al&#46;&#44; 2008&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; medication number&#44; instrumental activities of daily living &#40;IADLs&#41;&#44; ADLs&#44; cognitive status&#44; nutritional status&#44; risk of developing pressure soresco-morbidity and living status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Help predict the longevity of hospitalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Validated predominantly for hospitalized patients only&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Measures of frailty in end stage renal disease&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study authors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Frailty measurement tool used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcomes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansen et al&#46; &#40;2007&#41;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2275 incident haemodialysis &#40;HD&#41; patients of Dialysis Morbidity and Mortality Wave 2 study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty was independently associated with higher risk of death &#40;adjusted hazard ratio &#91;HR&#93; 2&#46;24&#44; 95&#37; confidence interval &#91;CI&#93; 1&#46;60&#8211;3&#46;15&#41; and composite of death or hospitalization &#40;adjusted HR 1&#46;63&#44; 95&#37; CI 1&#46;41&#8211;1&#46;87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bao et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1576 incident HD patients from the comprehensive dialysis study cohort of the United States renal data system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#37; prevalence of frailtyFrail patients had increased mortality &#40;HR 1&#46;57&#44; 95&#37; CI 1&#46;25&#8211;1&#46;97&#41; and faster time to hospitalization &#40;HR 1&#46;26&#44; 95&#37; CI 1&#46;09&#8211;1&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146 maintenance HD patients at single centre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intermediate frailty and frailty were associated with a 2&#46;7 times &#40;95&#37; &#40;CI&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;02&#8211;7&#46;07&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;046&#41; and 2&#46;6 times &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;04&#8211;6&#46;49&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; greater risk of death independent of age&#44; sex&#44; comorbidity&#44; and disability&#46;Frailty was associated with 1&#46;4 times &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#8211;2&#46;03&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41; more hospitalizations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95 maintenance HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty independently predicted a 3&#46;09-fold &#40;95&#37; CI&#58; 1&#46;38&#8211;6&#46;90&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; higher number of falls&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alfaadhel et al&#46; &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Frailty Scale &#40;CFS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">390 patients on maintenance HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR for mortality associated with each 1-point increase in the CFS was 1&#46;22 &#40;95&#37; CI&#44; 1&#46;04&#8211;1&#46;43&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al&#46; &#40;2017&#41;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified cardiovascular health study frailty &#40;CHS&#41; phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1255 HD and 403 PD patients&#44; multicentre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty was associated with hospitalization &#40;adjusted HR&#44; 1&#46;80&#59; 95&#37; CI&#58; 1&#46;38&#8211;2&#46;36&#41; and mortality &#40;HR&#44; 2&#46;37&#44; 95&#37; CI&#58; 1&#46;11&#8211;5&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al&#46; &#40;2017&#41;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multidimensional frailty score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 elderly incident HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality or cardiovascularHospitalization for frailty groupHR 23&#46;58 &#40;1&#46;61&#8211;346&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2018&#41;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1975 HD patients on transplant wait list&#44; multicentre cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty associated with increased mortality &#40;HR 2&#46;19&#44; 95&#37; CI&#58; 1&#46;26&#8211;3&#46;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fitzpatrick et al&#46; &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">48</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">370 incident HD patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease &#40;PACE&#41; study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frail patients had 1&#46;66-fold increased mortality risk &#91;95&#37; &#40;CI&#41; 1&#46;03&#8211;2&#46;67&#93;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansen et al&#46; &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">49</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">727 maintenance HD patience&#44; multicentre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR of 2&#46;73 for one frailty component fulfilled to 10&#46;07 for five components&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aurora et al&#46; &#40;2020&#41;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&#44; short physical performance battery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">117 elderly &#40;&#62;69 years&#41; HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frail patients had higher mortality risk&#44; HR 2&#46;6 &#40;95&#37; CI 0&#46;9&#8211;7&#46;9&#41; versus non frail at 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Studies on outcomes in patients with frailty in end stage renal disease&#46;</p>"
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Review
Frailty in end stage renal disease: Current perspectives
Fragilidad en la enfermedad renal en etapa terminal: perspectivas actuales
Shankar Prasad Nagarajua, Srinivas Vinayak Shenoya, Ankur Guptab,1,
Corresponding author
parthankur@yahoo.com

Corresponding author.
a Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
b Department of Medicine, Whakatane Hospital, New Zealand
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Frailty is a state of increased vulnerability to physical stressors like illness which leads to poor clinical outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">1</span></a> It is a condition usually found in elderly people and occurs as a result of progressive and sustained degeneration in multiple physiological systems in our body&#46; This is further worsened because of a decline in psychological health and inadequate social support&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">1&#8211;3</span></a> The prevalence of frailty is around 11&#37; in elderly without end stage renal disease &#40;ESRD&#41;&#44; whereas in patients with ESRD on dialysis it is more than 60&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">4&#44;5</span></a> It is characterized by weakness&#44; balance and motility issues&#44; and a decreased ability to resist stressors&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">6&#44;7</span></a> Impaired physical function&#44; sarcopenia&#44; and an increased risk of falls are hallmarks of the frailty syndrome&#46; Other adverse health outcomes include fractures&#44; hospitalization&#44; institutionalization&#44; disability&#44; dependence&#44; dementia&#44; poor quality of life&#44; and death&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">8</span></a> Frailty in chronic kidney disease &#40;CKD&#41; has been described as &#8220;senescent nephropathy&#8221; &#8211; a state characterized by a synergistic decline in physical and renal function&#44; proposed to be caused by increased levels of inflammation associated with each condition&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">6</span></a> Inspite of being an important prognostic marker&#44; frailty screening is yet to be widely implemented in routine renal care&#46; Patients with CKD&#44; especially ESRD are at a high risk of being frail&#46; Though there are many frailty measuring tools available&#44; the optimal means of screening for frailty in patients with kidney disease remains perplexing&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathogenesis of frailty in ESRD is multifactorial and is different from the general population since uraemia and dialysis are significant contributors&#46; Additionally&#44; standard management of ESRD&#44; including kidney replacement therapies&#44; may have a lower benefit or may be even potentially harmful in the presence of frailty&#46; Recently&#44; several interventions to modify frailty in ESRD have been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">9</span></a> In this review&#44; we highlight the importance of frailty screening in ESRD&#44; different tools for its measurement and its pathogenesis&#46; We also recapitulate the available evidence on frailty as a predictor of poor clinical outcomes&#44; as well as current guidelines for its management&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definitions and frailty measurement tools</span><p id="par0015" class="elsevierStylePara elsevierViewall">Frailty has been defined as a state of increased vulnerability to stressors like illness or trauma due to degeneration in multiple systems in our body leading to poor outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">1</span></a> Recently efforts have been put to create an operational definition for frailty&#44; so that it aids in its identification and severity&#46; In literature&#44; two principal concepts are described&#58; the Fried Phenotype Model of Frailty&#44; which focuses frailty as a physical phenotype characterized by sarcopenia&#44; and the other more holistic Frailty index &#40;Cumulative Deficit Model of Frailty&#41; which additionally incorporates other domains like comorbidities and psychological conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">10&#8211;14</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Frailty Phenotype &#40;FP&#41; is described as &#8216;a clinical syndrome involving at least three of the following&#58; unintentional weight loss&#44; self-reported exhaustion&#44; weakness&#44; slow walking speed and low physical activity&#8217;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; The presence of one or two of the above characteristics defines a patient as pre-frail&#46; In FP&#44; the measures of weakness and walking speed examination is cumbersome and time consuming&#46; So the FP has been modified in an attempt to reduce the burden of data collection by several studies on CKD populations which have used modified versions of the FP&#44; where questionnaire-based assessments for the objective measures of weakness and slowness are used&#46; Though these methods may overestimate the prevalence of frailty&#44; they also predict outcomes similar to FP&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">15&#8211;18</span></a> A study demonstrated that modified FP was independently associated with increased mortality risk in dialysis-dependent CKD &#91;HR 2&#46;24 &#40;95&#37; CI 1&#46;60&#8211;3&#46;15&#41;&#93; and also with an increased risk of the combined endpoint of hospitalization or death &#91;HR 1&#46;56 &#40;95&#37; CI 1&#46;36&#8211;1&#46;79&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">16</span></a> Similar to the FP&#44; the short physical performance battery &#40;SPPB&#41; is comprised of three physical assessments&#58; standing balance&#44; gait speed&#44; and a chair stand test&#46; Like the FP&#44; its strengths also lie in its objectivity&#46; In addition&#44; it provides a range of scores&#44; from 0 &#40;worst performance&#41; to 12 &#40;best performance&#41;&#44; allowing some quantification of a patient&#39;s level of frailty&#46; Importantly&#44; in patients with CKD&#44; the SPPB is reliable&#44; <a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">19</span></a> associated with disease progression and is predictive of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">20</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">A contrasting and holistic approach to the Cumulative Deficit Model of Frailty was described in the older population&#46; <a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">11</span></a> A remodification of this model included a total of 70 variables consisting of a variety of medical&#44; psychological and functional impairments&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> This led to the creation of a more global and complete frailty assessment&#44; the frailty index &#40;FI&#41;&#46; FI score was calculated by dividing the total number of deficits for an individual patient by all the predetermined clinical variables&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">3</span></a> A study compared FI with FP in elderly individuals and demonstrated that these operational definitions of frailty correlated moderately well with each other&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">12</span></a> They categorized participants as robust&#44; pre-frail &#40;intermediate frailty&#41; and frail as per FP&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">12</span></a> FI and FP were found to be comparable in frailty assessment in CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">21</span></a> But the FI is demanding to implement into routine clinical care&#44; as at least 30 variables are required to calculate the score making it a relatively time-consuming alternative&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">22&#44;23</span></a> However&#44; with the advent of electronic health records&#44; it may be possible to surpass this challenge&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The Groningen frailty indicator &#40;GFI&#41; is another multidimensional method of assessing frailty&#46; It consists of 15 questions across 8 domains&#44; including mobility&#44; vision&#44; hearing&#44; nutrition&#44; comorbidity&#44; cognition&#44; psychosocial&#44; and physical fitness&#46; The absence of physical testing and a better assessment of psychosocial status makes its afavoured screening test&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a> GFI was equally predictive of death and hospitalization in CKD population as other approaches&#44; but it failed to distinguish specific deficits&#44; especially of a physical nature&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">25</span></a> This could be due to the reason that physical impairment is screened with a single question&#44; asking the patient to rate their fitness from 0 to 10&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The multidimensional prognostic index &#40;MPI&#41; has been developed to predict the longevity of hospitalized adults&#46; In MPI&#44; frailty status is assessed through eight individual assessments including function &#40;activities of daily living&#41;&#44; polypharmacy&#44; mental status&#44; nutrition&#44; comorbidity&#44; risk of pressure sores and social circumstances&#46; Deficits in each domain are graded as 0 &#40;none&#41;&#44; 0&#46;5 &#40;minor&#41;&#44; or 1 &#40;major&#41;&#44; and then averaged&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">26</span></a> A score greater than 0&#46;66 is indicative of frailty and associated with increased hospital mortality and length of stay in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">27</span></a> In the elderly CKD population&#44; the addition of the MPI to the estimated GFR drastically improved prediction of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">28</span></a> A study revealed that maintenance haemodialysis &#40;HD&#41; patients had higher MPI scores than the global geriatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">29</span></a> The limitation of the MPI score is that it is only been validated in admitted CKD patients and needs endorsement before generalization to the outpatient CKD population&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally&#44; to produce a simple yet global frailty assessment for screening purposes&#44; a clinical frailty scale &#40;CFS&#41; has been proposed&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> Simplicity is the hallmark of the CFS when compared to other methods of assessing frailty&#46; CFS relies on clinical judgement alone and higher scores on the CFS were associated with an increased risk of death &#91;HR 1&#46;30 &#40;95&#37; CI 1&#46;27&#8211;1&#46;33&#41;&#93; and hospitalization &#91;HR 1&#46;46 &#40;95&#37; CI 1&#46;39&#8211;1&#46;53&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> In its original form&#44; the CFS was a 7-point scale<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a> and later updated to include nine descriptors&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">23</span></a> The CFS has been shown to have similar predictive characteristics as the FP and FI in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">12&#44;13</span></a> In addition&#44; like the SPPB and FI&#44; the CFS is graduated and allows for monitoring of changes in frailty severity over time&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">30</span></a> CFS scores at dialysis initiation are associated with higher mortality<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">31</span></a> and worse health-related quality of life scores in older patients on assisted peritoneal dialysis &#40;PD&#41; and HD&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">32</span></a> CFS seemingly agreed with the FP better than the SPPB and FI&#44; suggesting that the CFS may be a valuable option for accurate screening of frailty when it is not practical to perform a physical assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">33</span></a> So CFS is a promising frailty screening tool that could be incorporated into routine clinical renal care&#46; The limitations of the CFS are being a subjective tool and yet to have robust validation data in CKD&#46; Currently there is no consensus as to which measurement of frailty is superior&#46; Since all approaches are associated with clinical outcomes&#44; it is more important that efforts are made to identify frailty in ESRD&#44; regardless of the adopted methodology&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathogenesis of frailty in ESRD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">The pathogenesis of frailty in ESRD is multifactorial&#46; Reduced intake contributes to sarcopenia and later physical frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">35</span></a> The contributing factors for loss of appetite include the uraemic milieu&#44; inflammation&#44; comorbid illnesses&#44; medications and associated low mood and cognitive impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;36</span></a> Physical inactivity is the other important factor in CKD which contributes for sarcopenia&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">37</span></a> The increased levels of pro-inflammatory cytokines like interleukin &#40;IL-6&#41; and tumour necrosis factor alpha &#40;TNF-a&#41;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">38</span></a> leads to impaired signalling of the anabolic hormones insulin and insulin-like growth factor-1 &#40;IGF&#41;-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;39</span></a> This leads to muscle protein breakdown via the caspase-3 and ubiquitin proteasome system&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">38</span></a> Metabolic acidosis also activates caspase-3 and inhibits intracellular signalling of insulin and IGF-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;38</span></a> All of the above results in a state of protein catabolism leading to sarcopenia&#46; It has been shown that 1&#44; 25&#40;OH&#41;<span class="elsevierStyleInf">2</span> D is a determinant of physical function and muscle size in those with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">40</span></a> So deficiency of Vitamin D also may be a factor in the development of frailty in CKD&#46; Finally&#44; cellular senescence&#44; loss of telomeric structures&#44; mitochondrial dysfunction&#44; increased free radical production and poor DNA repair capability are important in the ageing process and the development of frailty&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">41</span></a> These processes occur prematurely in CKD population ultimately leading to sarcopenia&#44; vascular dysfunction and progressive organ damage&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">42</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Frailty as a marker of prognosis in ESRD</span><p id="par0050" class="elsevierStylePara elsevierViewall">Fraility is independently predictive of adverse outcomes&#44; including falls&#44; hospitalization and mortality in the elderly general population&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> Furthermore&#44; the presence of intermediate frailty &#40;or pre-frailty&#41;&#44; was predictive of becoming frail over the next 3&#8211;4 years&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a> Studies that were done in the ESRD patients also show a similar pattern&#46; A study demonstrated that frailty at dialysis initiation was associated with an increased risk of mortality &#91;hazard ratio &#91;HR&#93; 1&#46;57 &#40;95&#37; CI 1&#46;25&#8211;1&#46;97&#41;&#93; and first hospitalization &#91;HR 1&#46;26 &#40;95&#37; CI 1&#46;09&#8211;1&#46;45&#41;&#93;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">5</span></a> Another study categorized dialysis patients as either non-frail&#44; intermediately frail or frail&#46; It was seen that proportion of participants admitted to hospital on two or more occasions over the subsequent year after enrolment was 43&#37; for frail dialysis patients compared to 28&#37; for nonfrail dialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a> The 3-year mortality was 40&#37; for frail dialysis patients&#46; 34&#37; of those categorized as intermediately frail patients died within the 3-year follow-up period&#44; compared with only 16&#37; of those who are non-frail&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a> Thus&#44; differentiating degrees of frailty offers even greater clinical utility&#46; Another study by the same group assessed frailty in 95 dialysis patients for falls&#46; Over a 6&#46;7-month follow-up period&#44; there were 3&#46;09-fold &#40;95&#37; CI 1&#46;38&#8211;6&#46;90&#41; more falls in frail patients&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">44</span></a> The other studies in dialysis patients are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; With the present evidence&#44; it is clear that assessment of frailty is an important prognostic indicator in dialysis patients and it predicts mortality&#44; hospitalization and falls irrespective of the methods used for assessment&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Current guidance</span><p id="par0055" class="elsevierStylePara elsevierViewall">Among present guidelines on dialysis&#44; the frailty is being addressed in the 2016 European renal best practice &#40;ERBP&#41; guideline&#46; Frailty screening should be considered in all older adults who are not otherwise at risk of imminently dying or at low risk for progression to ESRD&#46; It emphasizes that frailty scores may help in providing additional information during assessment and shared decision-making on the planning of patients&#46; No specific screening test was recommended&#46; It suggested that after an initial assessment&#44; functional status be reassessed every 6&#8211;8 weeks for dialysis patients&#46; It also recommends exercise therapy and dietary interventions as potential means of modifying frailty and frailty assessment to be a part of advanced care planning &#40;ACP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a> In 2015&#44; Kidney Disease&#58; Improving Global Outcomes &#40;KDIGO&#41; in partnership with the International Society of Nephrology &#40;ISN&#41;&#44; hosted a controversies conference on supportive care in CKD&#46; The conference highlighted the need for identifying patients pre-dialysis and as well on dialysis who may be frail and may not benefit or may worsen with continuation of dialysis&#46; There was no consensus on ideal tools to decide on patients requiring conservative care&#46; However&#44; there was a stress on using appropriate tools like the modified Karnofsky activity scale or screening activities of daily living&#44; use of &#8220;surprise question&#8221; to assess and prognosticate the patients for conservative care versus conventional kidney replacement therapy &#40;KRT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">52</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Management</span><p id="par0060" class="elsevierStylePara elsevierViewall">Frail patients with CKD are a distinct population&#44; their risk profile will be different from fit patients&#46; Although&#44; frailty most commonly follows a downward trajectory&#44; there is growing evidence to suggest that it can be improved with intervention&#46; A holistic assessment with individualized assessment and targeted management strategy will be the key&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">First and foremost&#44; it is important to address undernutrition&#46; The possible causes for decreased appetite&#44; like uraemia&#44; metabolic acidosis&#44; intercurrent illness&#44; medications&#44; and comorbid conditions such as depression should be identified and treated&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">35&#44;39&#44;53</span></a> Though there might not be a survival benefit &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#41;&#44; but oral nutritional supplementation was associated with fewer hospital admissions&#44; in those with ESRD and hypalbuminaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">54</span></a> The dietary phosphate restriction in ESRD patients with frailty may outweigh the benefits and result in further worsening of undernutrition and protein-energy&#46; So dietary phosphate restriction should be individualized to allow adequate nutritional intake&#46; Recent guidelines by ERBP in 2016 state that &#8216;preserving nutritional status should prevail over any other dietary restriction&#8217;&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Exercise has well-established&#44; multifaceted benefits for improving the frailty in ESRD patients&#46; Dialysis patients&#44; in general&#44; live a sedentary lifestyle&#46; Decreased physical activity in elderly haemodialysis patients has been associated with a risk of increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">55</span></a> Exercise helps in improvements in muscle strength&#44; cardiovascular function&#44; physical function and health-related quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">56</span></a> Even a modest amount of exercise in severely frail patients have shown a variety of benefits like better mobility&#44; independence&#44; quality of life&#44; bone mineral density and reduced falls&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">57</span></a> Aerobic&#44; resistance and combined exercise programmes have demonstrated substantial benefits&#46; Both intradialytic and interdialytic exercise programmes are helpful in improving frailty&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">58&#8211;60</span></a> Regular exercise increased muscle mass and reduced systemic inflammation in CKD population&#46;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">61&#44;62</span></a> A study concluded that exercising during non-dialysis days was most effective&#44; but intra-dialysis exercising was both effective and preferable&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">59</span></a> Individualized exercise programme should be part of targeted therapy for all frail ESRD patients and seems to be valuable regardless of the type or mode of exercise&#46; Apart from nutritional care and exercise&#44; falls prevention measures&#44; and timely control of ESRD complications&#44; the inclusion of frailty management as part of ACP may help frail ESRD patients to improve their overall outcomes&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Choice of KRT in frail ESRD</span><p id="par0075" class="elsevierStylePara elsevierViewall">Dialysis and transplant are significant stressors to an ESRD patient&#44; and therefore should only be expected to benefit who are adequately robust&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">63</span></a> The severity of frailty significantly impacts on patient&#39;s experience of different kidney replacement therapies&#46; As a patient&#39;s frailty severity progresses&#44; the nephrologist&#39;s focus should shift to potentially modifying care to less invasive treatment options like incremental dialysis or conservative management&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Incremental HD is one of the proposed strategies for limiting frailty&#46; It has been shown to slow the loss of residual kidney function in ESRD&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">64</span></a> It means to start with one&#47;week or two&#47;week HD regimens which are shorter or less frequent than standard three times per week maintenance therapy&#46; Later it can be increased over time to accommodate a further decline in residual kidney function&#46; By starting frail patients on incremental HD&#44; the physiologic stress of dialysis is decreased&#46; It leads to reduced post dialysis recovery time&#44; less interference with social and family life&#44; and ultimately better quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">65</span></a> Incremental PD may be considered as an option as well&#46; Home HD &#40;either conventional&#44; frequent&#44; or intensive&#41; in frail patients may be another solution&#46; But the evidence on peritoneal or home HD is not substantial&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">32&#44;66</span></a> Similar to PD&#44; home HD allows greater involvement of family&#44; no travel burden of in-centre haemodialysis&#44; and more flexibility&#46; An important future consideration is an evaluation of the impact of PD or home HD on frailty&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Kidney transplant is a significant physiologic stress to frail ESRD patients&#46; Frail patients have an increased risk of postoperative complications and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">67&#44;68</span></a> It is currently unclear at what degree of frailty the risks of transplantation outweigh the benefits&#46; But transplant itself may be one of the &#8220;interventions&#8221; that could improve a patient&#39;s frailty significantly&#46; Although frailty initially worsens post-transplant&#44; it has been shown to improve as early as three months post transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">69</span></a> A study showed a similar survival benefit in frail and fit patients by 9 months post-transplant&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">70</span></a> As frailty advances&#44; the risks and benefits of more invasive options for KRT should be reassessed&#46; The option of conservative treatment with symptomatic management without any dialytic support must be explored with patients and families&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">51</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Frailty is highly prevalent in ESRD patients independent of age&#46; The pathogenesis of frailty in ESRD is multifactorial&#46; Frail patients are likely to have higher morbidity and mortality compared to non-frail counterparts&#46; Many frailty screening tools have been studied and validated in different settings of CKD and ESRD&#46; In the absence of a consensus on the ideal screening tool&#44; the emphasis should be placed on to use any one of the tools to identify frailty&#46; A holistic individual assessment to address risk factors that may exacerbate its progression should be considered&#46; Adequate nutritional intake is essential and individualized exercise programmes should be offered to all frail ESRD patients along with psychological and social support&#46; Though the ERBP in 2016 and KDIGO in 2015 have attempted to incorporate frailty screening in ESRD population&#44; it is yet to receive widespread acceptance&#46; It is the time for the nephrology community to include it in routine practice to inform discussions with patients about conservative treatment or select a suitable mode of kidney replacement therapy&#44; tailor the dialysis prescription as per the needs of the individual rather have a &#8220;one size fits all&#8221; approach&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Data availability</span><p id="par0095" class="elsevierStylePara elsevierViewall">Not required&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethical approval</span><p id="par0100" class="elsevierStylePara elsevierViewall">The procedures followed were in accordance with Declaration of Helsinki and its revisions&#46; Informed consent from the subjects is not required</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">Not required&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Definitions and frailty measurement tools"
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          "titulo" => "Pathogenesis of frailty in ESRD &#40;Fig&#46; 1&#41;"
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          "titulo" => "Frailty as a marker of prognosis in ESRD"
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          "titulo" => "Conclusion"
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            0 => "Frailty"
            1 => "End stage renal disease"
            2 => "Dialysis"
            3 => "Sarcopenia"
            4 => "Senescent nephropathy"
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            0 => "Fragilidad"
            1 => "Enfermedad renal en etapa terminal"
            2 => "Di&#225;lisis"
            3 => "Sarcopenia"
            4 => "Nefropat&#237;a senescente"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Frailty is common in end stage renal disease &#40;ESRD&#41; and is a marker of poor outcomes&#46; Its prevalence increases as chronic kidney disease &#40;CKD&#41; progresses&#46; There are different measurement tools available to assess frailty in ESRD&#46; The pathogenesis of frailty in ESRD is multifactorial including uraemia and dialysis related factors&#46; In this current review&#44; we discuss the importance of frailty&#44; its pathogenesis&#44; screening methods&#44; prognostic implications and management strategies in context of ESRD&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La fragilidad es com&#250;n en la enfermedad renal en etapa terminal &#40;ESRD&#41; y es un marcador de malos resultados&#46; Su la prevalencia aumenta a medida que avanza la enfermedad renal cr&#243;nica &#40;ERC&#41;&#46; Hay diferentes herramientas de medici&#243;n disponibles para evaluar la fragilidad en la ERT&#46; La patogenia de la fragilidad en la ESRD es multifactorial que incluye uremia y factores relacionados con la di&#225;lisis&#46; En esta revisi&#243;n actual&#44; discutimos la importancia de la fragilidad&#44; su patog&#233;nesis&#44; m&#233;todos de cribado&#44; implicaciones pron&#243;sticas y estrategias de manejo en el contexto de la ESRD&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Ankur Gupta act as guarantor for other authors&#46;</p>"
        "identificador" => "fn0005"
      ]
    ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pathogenesis of frailty in end stage renal disease &#40;Abbreviations&#58; CNS &#8211; central nervous system&#44; CKD &#8211; chronic kidney disease&#44; MIA &#8211; malnutrition inflammation-atherosclerosis&#44; IGF &#8211; insulin like growth factor&#41;&#46;</p>"
        ]
      ]
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          0 => array:3 [
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tool&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Components&#47;domains&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Advantages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disadvantages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried&#39;s frailty criteria &#40;Fried et al&#46;&#44; 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physical &#8211; weight loss&#44; low physical activity&#44; exhaustion&#44; slowness&#44; weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Most commonly used and extensively validated in chronic kidney disease &#40;CKD&#41; and end stage renal disease &#40;ESRD&#41; populationObjective measures also used hence reproducible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Need to perform physical testsAssesses only physical domainCategorical grading of components&#44; hence may identify only moderate to severe casesWeight loss criteria may not be practical in dialysis patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Short Physical Battery performance &#40;Guralnik et al&#46;&#44; 1994&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physical &#8211; Balance&#44; gait&#44; strength&#44; and endurance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Validated in CKD and ESRD populationObjective assessmentRisk scoring is on a continuous scale hence can help identify mild cases and also monitor progress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Only physical domains assessedPhysical testing may be cumbersome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Groningen Frailty Indicator &#40;Steverink et al&#46;&#44; 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical&#44; cognitive&#44; social and psychological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No physical tests to be performed hence easierGives information of day to day functionality of the patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not well validated in CKD and ESRDSubjective assessment in many domainsLess sensitive to detect defects in physical domains&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Frailty Scale &#40;Rockwood et al&#46;&#44; 2005&#41;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical cognitive&#44; functional&#44; comorbid illness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Based on clinical judgement&#44; simple to useAllows for gradation and monitoring progress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Many components subjectiveVery fit ESRD patients will also be scored as 3 &#40;Managing Well&#41; on account of co-morbidityNot well validated CKD&#47;ESRD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty Index &#40;Rockwood and Mitnitsky 2001&#41;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; Physical&#44; cognition&#44; co morbid illness&#44; symptoms&#44; disabilities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Covers multiple domains&#44; which can be created specifically for a target populationPatients can be graded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time consuming to calculate because of mathematical nature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multidisciplinary prognostic index &#40;Pilotto et al&#46;&#44; 2008&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple &#8211; medication number&#44; instrumental activities of daily living &#40;IADLs&#41;&#44; ADLs&#44; cognitive status&#44; nutritional status&#44; risk of developing pressure soresco-morbidity and living status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Help predict the longevity of hospitalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Validated predominantly for hospitalized patients only&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Measures of frailty in end stage renal disease&#46;</p>"
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      ]
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        "etiqueta" => "Table 2"
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          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study authors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Frailty measurement tool used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcomes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansen et al&#46; &#40;2007&#41;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2275 incident haemodialysis &#40;HD&#41; patients of Dialysis Morbidity and Mortality Wave 2 study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty was independently associated with higher risk of death &#40;adjusted hazard ratio &#91;HR&#93; 2&#46;24&#44; 95&#37; confidence interval &#91;CI&#93; 1&#46;60&#8211;3&#46;15&#41; and composite of death or hospitalization &#40;adjusted HR 1&#46;63&#44; 95&#37; CI 1&#46;41&#8211;1&#46;87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bao et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1576 incident HD patients from the comprehensive dialysis study cohort of the United States renal data system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#37; prevalence of frailtyFrail patients had increased mortality &#40;HR 1&#46;57&#44; 95&#37; CI 1&#46;25&#8211;1&#46;97&#41; and faster time to hospitalization &#40;HR 1&#46;26&#44; 95&#37; CI 1&#46;09&#8211;1&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146 maintenance HD patients at single centre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intermediate frailty and frailty were associated with a 2&#46;7 times &#40;95&#37; &#40;CI&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;02&#8211;7&#46;07&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;046&#41; and 2&#46;6 times &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;04&#8211;6&#46;49&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; greater risk of death independent of age&#44; sex&#44; comorbidity&#44; and disability&#46;Frailty was associated with 1&#46;4 times &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;00&#8211;2&#46;03&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41; more hospitalizations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95 maintenance HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty independently predicted a 3&#46;09-fold &#40;95&#37; CI&#58; 1&#46;38&#8211;6&#46;90&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; higher number of falls&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alfaadhel et al&#46; &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical Frailty Scale &#40;CFS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">390 patients on maintenance HD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR for mortality associated with each 1-point increase in the CFS was 1&#46;22 &#40;95&#37; CI&#44; 1&#46;04&#8211;1&#46;43&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al&#46; &#40;2017&#41;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Modified cardiovascular health study frailty &#40;CHS&#41; phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1255 HD and 403 PD patients&#44; multicentre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty was associated with hospitalization &#40;adjusted HR&#44; 1&#46;80&#59; 95&#37; CI&#58; 1&#46;38&#8211;2&#46;36&#41; and mortality &#40;HR&#44; 2&#46;37&#44; 95&#37; CI&#58; 1&#46;11&#8211;5&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al&#46; &#40;2017&#41;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multidimensional frailty score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 elderly incident HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality or cardiovascularHospitalization for frailty groupHR 23&#46;58 &#40;1&#46;61&#8211;346&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McAdams de Marco et al&#46; &#40;2018&#41;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1975 HD patients on transplant wait list&#44; multicentre cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frailty associated with increased mortality &#40;HR 2&#46;19&#44; 95&#37; CI&#58; 1&#46;26&#8211;3&#46;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fitzpatrick et al&#46; &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">48</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">370 incident HD patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease &#40;PACE&#41; study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frail patients had 1&#46;66-fold increased mortality risk &#91;95&#37; &#40;CI&#41; 1&#46;03&#8211;2&#46;67&#93;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansen et al&#46; &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">49</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frieds phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">727 maintenance HD patience&#44; multicentre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR of 2&#46;73 for one frailty component fulfilled to 10&#46;07 for five components&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aurora et al&#46; &#40;2020&#41;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fried phenotype&#44; short physical performance battery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">117 elderly &#40;&#62;69 years&#41; HD patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frail patients had higher mortality risk&#44; HR 2&#46;6 &#40;95&#37; CI 0&#46;9&#8211;7&#46;9&#41; versus non frail at 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Studies on outcomes in patients with frailty in end stage renal disease&#46;</p>"
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ISSN: 20132514
Original language: English
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