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and neutrophil-to-lymphocyte ratio &#40;NLR&#41; have begun to be used in kidney patients&#44; particularly as markers of inflammation&#44; endothelial damage and&#44; more recently&#44; as predictor of death&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this review was to perform an in-depth analysis of the pathophysiological bases of these indexes&#44; with special emphasis on the processes of inflammation and arteriosclerosis&#44; and their clinical utility in kidney patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Pathophysiological bases of the ratios</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Neutrophils</span><p id="par0020" class="elsevierStylePara elsevierViewall">In classical terms&#44; neutrophils are immature phagocytes with a short half-life&#46; They are known to have the ability to release proteolytic enzymes and oxygen free radicals&#44; actively contributing to the damage produced during inflammatory processes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In vascular territory&#44; neutrophils interact with the endothelium&#44; releasing various proteins from their granules that generate molecular instructions to recruit and activate other inflammatory cells&#46; Leukotrienes&#44; which also form part of the arsenal of neutrophils&#44; characteristically have significant capacity to evoke chemotaxis&#46; All these actions amplify the initial process and trigger a significant immunoregulatory effect&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">However&#44; classically&#44; the role of neutrophils in atherosclerosis was not given much importance in view of their relative absence in conventional histological studies due either to their short half-life or their phenotypic evolution to other cells &#40;for example&#44; macrophages or dendritic cells&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">That situation changed with the advent of new immunological markers &#40;such as Ly6G&#44; anti-MPO and CD66b&#41;&#44; as neutrophils have now been detected in early and advanced atherosclerosis lesions&#44; in subendothelial and intimal locations and even inside thrombi&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another property of neutrophils is their ability to produce extracellular tissue scaffolds &#40;Neutrophil Extracellular Traps&#41;&#44; which are designed to trap pathogens&#46; Interestingly&#44; however&#44; these supramolecular complexes have also been implicated in the atherosclerosis process&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In a hyperlipidaemic environment&#44; activated neutrophils can worsen endothelial function&#44; creating proinflammatory positive feedback and decreasing vasodilation&#46; Added to that&#44; the adhesion of neutrophils to the endothelium stimulates the release of secretory vesicles that perpetuate the endothelial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The presence of activated neutrophils has also been associated with the destabilisation of atherosclerotic plaques through oxygen free radicals and some extracellular matrix proteinases &#40;matrix metalloproteinases &#91;MMP&#93;&#41;&#46; In some experimental studies&#44; treatment with fluvastatin decreased these MMP and increased collagen&#44; a situation that produces negative feedback decreasing neutrophil infiltration&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Therefore&#44; it is now accepted that activated neutrophils are key elements in atherogenesis and subsequent cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">7&#44;8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Platelets</span><p id="par0060" class="elsevierStylePara elsevierViewall">Platelets are nucleated cell fragments derived from megakaryocytes&#46; Their haemostatic and prothrombotic function has been widely studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">10&#44;11</span></a> However&#44; their proinflammatory function has been investigated only recently&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">10</span></a> Platelets interact with numerous immune cells&#44; but their relationship with endothelial cells and leucocytes are among the most important&#46; This association has been fundamental in understanding the pathophysiology of vascular inflammation&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">10&#44;12</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In atherosclerosis&#44; the presence of inflammation inhibits the antiadhesion properties of platelets&#44; which tends to increase the interaction of platelets with the endothelium&#46; This circumstance sets off a series of inflammatory effects in cascade&#44; analogous to the phenomena that occur in thrombosis and haemostasis&#46; Greater platelet activation triggers the secretion of cytokines and&#44; in turn&#44; creates a &#8220;chemotasis&#8221; effect that some authors have termed &#8220;inflamed endothelium&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">There is also an important interaction between platelets and leucocytes in the context of atherogenesis&#44; promoting cell recruitment to the area of the lesion through selectins and integrins&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">13&#44;14</span></a> Specifically&#58; connective tissue activator peptide III &#40;CTAP-III&#41; is transformed into neutrophil activating protein-2 &#40;NAP-2&#41;&#44; which in vitro induces neutrophil and monocyte adhesion as well as transendothelial migration of neutrophils&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">15&#8211;17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Lymphocytes</span><p id="par0075" class="elsevierStylePara elsevierViewall">The effects of lymphocytes on atherosclerosis can be both deleterious due to the effect of Th1 cells and protective due to the action of regulatory Th2 and CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Foxp3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>cells &#40;Tregs&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The presence of oxidised LDL stimulates the activation of dendritic cells&#44; which favours the balance of T cells towards a predominance of the &#8220;pro-atherogenic&#8221; line including Th1 or Th17&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">18&#44;20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The Th2 lymphocytes&#44; through interleukin-19 &#40;IL-19&#41;&#44; induce an anti-inflammatory state that favours pathways such as GATA3 and Foxp3&#46; These pathways attenuate or decrease the atherosclerotic process&#46; Perhaps this may be the reason why an increase in circulating Th2 is associated with a lower risk of myocardial infarction&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">18&#44;21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The &#8220;good&#8221; Tregs cells are diminished in murine models of a hyperlipidaemic diet that leads to atherosclerosis&#46; This diet would increase the chemotaxis of the lymphocytes towards the aorta and promotes the development and progression of aortic atherosclerosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">18&#44;19&#44;22</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In relation to CD8 cells&#44; opinions of different authors are divided&#59; there are studies that consider that CD8 cells are pro-atherogenic&#44; but a subgroup of these cells &#40;CD8&#43; CD25&#43;&#41; would have the opposite effect&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Other less common cell lines also significantly influence the atherosclerosis process&#46; For example&#44; &#947;&#948; lymphocytes which produce interleukin-17 &#40;IL-17&#41; have been surprisingly found in the aortas of murine apoE -&#47;- models fed a Western diet&#46; NK &#40;natural killer&#41; cells&#44; whose primary function is to confront viruses and other pathogens as part of the body&#39;s innate defence system&#44; could contribute to atherosclerosis&#46; It has been demonstrated that in murine models without NK cells the atherosclerosis process was attenuated&#46; The involvement of NK cells in the rupture of the atherosclerotic plaque has also been described by some authors&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">23</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The B lymphocytes also affect the atherosclerotic process&#46; It is known that B1 cells protect against atherosclerosis&#46; However&#44; the role of B2 cells remains unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Inflammation</span><p id="par0110" class="elsevierStylePara elsevierViewall">Taken together all the information available<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">1&#44;2</span></a> it is concluded that these mentioned indexes could be a marker of inflammatory imbalance in which there is a predominance of effector cells &#40;pro-inflammatory effect&#41; mainly activated neutrophils and platelets&#44; over regulatory cells &#40;anti-inflammatory effect&#41;&#44; CD4 cells in particular&#46; However&#44; the model is complicated because&#44; as previously mentioned&#44; some lymphocyte cell subtypes have a dual effect&#46; For example&#44; a predominance of the subtype of T-helper 17 cells would result in increased production of IL-17 which is involved in atherogenic processes&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">First clinical uses of the ratios</span><p id="par0115" class="elsevierStylePara elsevierViewall">The first references to NLR are in relation to severe infections and changes in adrenocortical function in animals under stress&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">25&#8211;27</span></a> In later years&#44; the Ventafrida group mentions the leucocyte-to-lymphocyte ratio as a predictor of survival in patients with cancer cachexia&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In 1995&#44; Goodman et al&#46; published one of the first clinical uses of NLR in humans as a marker of acute appendicitis&#58; an NLR &#8805;3&#46;5 had a greater sensitivity for detecting the disease than the absolute number of leucocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">29</span></a> A year later&#44; it was used in conjunction with the ADA test for the diagnosis of pleural tuberculous&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">30</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Its use as a prognostic marker in cancer continues to extend to gastric and colorectal disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">31&#44;32</span></a> while also being applied in critically ill patients&#44; comparing it with other widely recognised scales&#44; such as APACHE II&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">33</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">From a cardiovascular point of view&#44; in 2006 Duffy et al&#46; published one of the first studies to link NLR levels prior to percutaneous coronary intervention with a higher subsequent mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">34</span></a> In 2008&#44; Papa et al&#46; described the NLR as a predictor of cardiac death in patients with stable coronary heart disease&#59; the patients at highest risk had an NLR above 2&#46;55&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">35</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The use of the PLR is more recent and was initially used as a marker in periampullary cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">36&#44;37</span></a> The first studies correlating the PLR with cardiovascular disease appeared in 2012&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Use in oncology</span><p id="par0140" class="elsevierStylePara elsevierViewall">Within this field&#44; inflammation has gained a great deal of interest both from the pathophysiological and prognosis point of view&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">39&#44;40</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Neutrophils inhibit the suppressive function of CD8 cells&#46; That is why an increase in neutrophils would be associated with a worse response to cancer cells&#46; In contrast&#44; the presence of lymphocytes in some cancers has been associated with a better response to treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">41</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The NLR has specifically been described as a prognostic marker in different types of cancers such as breast&#44; colon&#44; kidney&#44; urothelium and pancreas&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">39&#44;42</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The PLR has also been used as a good prognostic marker in colorectal&#44; gastroesophageal&#44; hepatic&#44; pancreatic&#44; ovarian and breast cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Use in cardiovascular disease</span><p id="par0160" class="elsevierStylePara elsevierViewall">In previous sections&#44; we have discussed the influence of neutrophils&#44; platelets and lymphocytes on systemic inflammation and their relationship with the arteriosclerotic process&#46; The arteriosclerotic process is associated with a greater long-term cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">24</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In coronary heart disease&#44; the NLR is associated with a higher degree of coronary obstruction&#44; worse prognosis and a higher frequency of major cardiovascular events &#40;acute myocardial infarction&#44; revascularisation and death of cardiovascular cause&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">24&#44;44</span></a> The NLR predicts death not only in stable patients but also in acute disease&#46; In some studies&#44; a high NLR value prior to a percutaneous intervention was associated with higher rates of stent restenosis<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">45</span></a> and post-intervention mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">46</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In cerebrovascular disease&#44; the NLR is a good predictor of death&#44; functional dependence and severity of stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">24</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">In peripheral vascular disease&#44; the NLR is associated with greater disease severity and high rates of both critical stenosis and amputation&#46; If we consider treated patients&#44; a high NLR is associated with a higher rate of amputation in the first month post-embolectomy and with graft failure in revascularisation surgery&#46; In view of these findings&#44; its association with higher mortality rates is not surprising&#44; whether in patients receiving active treatment or those managed conservatively&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">24</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">In patients with diabetes&#44; the NLR can also be a marker of major cardiovascular events&#44; even more accurate than albuminuria&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">47</span></a> Other authors have even found a significant association between a high NLR values and HOMA index&#46; This finding shows the probable association between inflammation and insulin resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">48</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Some studies have linked the NLR with endothelial dysfunction in clinically asymptomatic patients&#46; Mart&#237;nez-Urbistondo et al&#46; found a good correlation between high NLR and an abnormal urinary albumin&#47;creatinine ratio&#46; Interestingly&#44; in this same study&#44; patients on treatment with statins had a tendency to have a lower NLR&#44; probably due to the anti-inflammatory effect of these drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Use in kidney disease</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Acute kidney injury</span><p id="par0190" class="elsevierStylePara elsevierViewall">Nephrologists are eager to find a parameter capable to predict for acute kidney injury &#40;AKI&#41;&#46; In cardiac surgery&#44; different markers such as cystatin C&#44; interleukin-18&#44; kidney injury molecule-1 &#40;KIM-1&#41;&#44; N-acetyl-beta-<span class="elsevierStyleSmallCaps">d</span>-glucosaminidase and neutrophil gelatinase-associated lipocalin have been tested&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">3</span></a> However&#44; their use is not widespread and is generally confined to the scope of clinical research&#46; Some recent retrospective studies have shown their interest in the NLR as a marker of AKI in postoperative cardiac patients&#46; A study of 590 patients showed that a high NLR in the postoperative period after cardiac surgery could be a predictor of AKI&#46; The authors suggest that the intraoperative ischaemia and the use of an extracorporeal circuit may activate the renal endothelial cells and create a renal inflammatory state that could lead to the development of AKI&#46; In this study&#44; the one-year overall mortality rate was higher in quartiles 3 and 4 of the postoperative NLR&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Kidney disease progression</span><p id="par0195" class="elsevierStylePara elsevierViewall">Some studies have found a negative correlation between the NLR and the glomerular filtration rate&#46; Tonyali et al&#46; found that an NLR &#62;3&#46;18 in patients undergoing radical or partial nephrectomy was associated with an increased risk &#40;almost 3 times&#41; of developing CKD &#40;defined by a glomerular filtration rate &#60;60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">50</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In another recent study&#44; Lu et al&#46; reported that a high NLR was associated with a greater likelihood of renal replacement therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">51</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Vascular access stenosis</span><p id="par0205" class="elsevierStylePara elsevierViewall">Native or prosthetic arteriovenous fistulas are the most efficient types of vascular access in the field of haemodialysis and the main reason for dysfunction is stenosis&#46; Stenosis occurs due to the development of venous intimal hyperplasia caused by what is initially damage to the endothelium&#44; but which goes on to trigger a series of detrimental effects &#40;oxidative stress&#44; inflammation&#44; endothelial dysfunction and migration of neointimal cells from alternative areas&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">52</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Microscopicaly&#44; venous intimal hyperplasia is similar to atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">53</span></a> The mechanisms related to the stenosis of native and prosthetic fistulas could therefore be analogous to those described in coronary procedures&#44; in which there is an inflammatory imbalance and markers such as the NLR are elevated&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">54</span></a> With this premise&#44; several studies have suggested that the NLR could be a good marker of stenosis and re-stenosis of native and prosthetic arteriovenous fistulas&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">53&#44;54</span></a> One of these studies reports an NLR cut-off point &#8805;2&#46;7 for the determination of stenosis&#44; with an ROC curve and AUC of 0&#46;893&#44; representing a sensitivity of 98&#46;4&#37; and a specificity of 75&#37;&#46;53 However&#44; these are cross-sectional or retrospective studies with a low level of scientific evidence&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">53&#44;54</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resistance to erythropoietin and inflammation</span><p id="par0215" class="elsevierStylePara elsevierViewall">In the field of haemodialysis&#44; patients with resistance to erythropoietin have&#44; independently&#44; higher morbidity and mortality rates&#46; One of the factors that most influences resistance to erythropoietin is the patients&#8217; own inflammatory state&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">55</span></a> In the last few years&#44; studies have analysed the association between NLR and PLR&#44; with resistance to erythropoietin based on inflammation as a common link&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">56</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">It has been suggested that the PLR could be a good marker of inflammation in the population with chronic kidney disease category G5&#46; Recent publications consider that the PLR has a better predictive value for diagnosing inflammation than the NLR&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">1&#44;2</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Mortality rates in patients with chronic kidney disease</span><p id="par0225" class="elsevierStylePara elsevierViewall">Also in the last few years a number of studies have assessed the importance of the NLR and PLR as markers of death in patients with advanced chronic kidney disease&#44; patients on haemodialysis and&#44; more recently&#44; those on peritoneal dialysis&#46; A relationship has been found between high values for these ratios and higher total and cardiovascular mortality rates in renal patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">51&#44;57&#8211;63</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0230" class="elsevierStylePara elsevierViewall">It is suggested that both a high baseline NLR and increases in the NLR could be related to a greater requirement for renal replacement therapy and higher mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">63</span></a> The cut-off point proposed by some authors from which the risk would be significantly elevated is around an NLR &#8805;3&#46;5&#46; The strong association between a high NLR and low levels of serum albumin strengthen the pathophysiological grounds for NLR as a marker of death&#46; Furthermore&#44; the greater predictive utility that NLR could provide over albumin is that its elevation in blood is faster &#40;6&#8211;8<span class="elsevierStyleHsp" style=""></span>h&#41; than the decrease in albumin &#40;19&#8211;21 days&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">64</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">In relation to the PLR&#44; there are not enough data to define a definitive cut-off point&#46; However&#44; a recent study with over 100&#44;000 incident patients on haemodialysis has established a J-curve pattern for death&#58; values less than 100 and greater than 300 would have higher mortality rates than those in the range 100&#8211;150&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">57&#8211;62&#44;64</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Key concepts</span><p id="par0240" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall">Neutrophils participate actively in the atherosclerosis process&#44; creating a proinflammatory environment through the Neutrophil Extracellular Traps&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0250" class="elsevierStylePara elsevierViewall">Activated neutrophils are involved in the destabilisation of atherosclerotic plaques&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0255" class="elsevierStylePara elsevierViewall">The interaction of platelets with the endothelium increases the migration of inflammatory cells to the area of the lesion by the use of platelet proteins&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0260" class="elsevierStylePara elsevierViewall">Th1 lymphocytes are pro-atherogenic&#44; while Th2 and Treg cells are anti-atherogenic&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0265" class="elsevierStylePara elsevierViewall">NK cells are involved in the rupture of the atherosclerotic plaque&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0270" class="elsevierStylePara elsevierViewall">In oncological disease&#44; a high NLR is described as a marker of poor prognosis in breast&#44; colon&#44; ovarian&#44; kidney&#44; urothelial and pancreatic cancers&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0275" class="elsevierStylePara elsevierViewall">In heart disease&#44; the NLR is associated with a greater frequency of major cardiovascular events&#44; a greater degree of coronary obstruction and a high rate of re-stenosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0280" class="elsevierStylePara elsevierViewall">In peripheral vascular disease&#44; the NLR is associated with greater disease severity&#44; a higher risk of amputation and graft failure in revascularisation surgery&#46; It is also associated with a higher mortality rate&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0285" class="elsevierStylePara elsevierViewall">The NLR has been found to be a good marker of AKI in postoperative cardiac patients&#44; of kidney disease progression and of a higher rate of admission in renal replacement therapy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0290" class="elsevierStylePara elsevierViewall">The PLR is related to resistance to erythropoietin and could be a better inflammation marker than the NLR in the population with chronic kidney disease category G5&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0295" class="elsevierStylePara elsevierViewall">The NLR is a good marker of death in patients with CKD&#44; with patients with an NLR &#8805;3&#46;5 being at the highest risk&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0300" class="elsevierStylePara elsevierViewall">The PLR has a J-curve pattern with respect to death in incident patients on haemodialysis&#46;</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
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        1 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Pathophysiological bases of the ratios"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Neutrophils"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Platelets"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Lymphocytes"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Inflammation"
            ]
          ]
        ]
        2 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "First clinical uses of the ratios"
        ]
        3 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Use in oncology"
        ]
        4 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Use in cardiovascular disease"
        ]
        5 => array:3 [
          "identificador" => "sec0050"
          "titulo" => "Use in kidney disease"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Acute kidney injury"
            ]
            1 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Kidney disease progression"
            ]
            2 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Vascular access stenosis"
            ]
            3 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Resistance to erythropoietin and inflammation"
            ]
            4 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Mortality rates in patients with chronic kidney disease"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Key concepts"
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        7 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflicts of interest"
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        8 => array:1 [
          "titulo" => "References"
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    "fechaAceptado" => "2018-11-11"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Valga F&#44; Monz&#243;n T&#44; Henriquez F&#44; Ant&#243;n-P&#233;rez G&#46; &#205;ndices neutr&#243;filo-linfocito y plaqueta-linfocito como marcadores biol&#243;gicos de inter&#233;s en la enfermedad renal&#46; Nefrologia&#46; 2019&#59;39&#58;243&#8211;249&#46;</p>"
      ]
    ]
    "multimedia" => array:1 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "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&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">Year&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">Marker&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">Patients&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">Cut-off points&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">Follow-up period&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">Results&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">Lu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">51</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">2018<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">Peritoneal dialysis&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">&#8805;4&#46;5&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">36 months&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">NLR &#8805;4&#46;5 associated with higher total and cardiovascular mortality rates&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">Catabay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">64</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">2017<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&#47;PLR&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">Incident patients on haemodialysis&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">NLR &#8805;6PLR &#8805;300&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">17 months&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">NLR &#8805;6 and PLR &#8805;300 associated with higher total mortality rate&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">Han Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">57</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">2017<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">Long-term haemodialysis&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">&#8805;3&#46;5&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">36 months&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">NLR &#8805;3&#46;5 associated with higher total and cardiovascular mortality rates&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">Sato et al&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">59</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">2017<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">Incident patients with diabetes on haemodialysis&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">&#8805;3&#46;5&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">36 months&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">Higher mortality rate in patients with NLR &#8805;3&#46;5&#46; AUC for NLR greater than for other inflammatory parameters&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">Tatar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">51</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">2016<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&#47;PLR&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">CKD Category G3-5&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 defined &#40;higher mortality rates in patients with mean baseline NLR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;05&#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">30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13 months&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">Higher mortality rates and need for renal replacement therapy programme in patients with high baseline NLR or in whom the NLR increased during follow-up&#46;PLR not associated with higher mortality rates or need for renal replacement therapy programme&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">Chen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">60</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">2016<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">CKD and peripheral vascular disease<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PTA&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">&#8805;3&#46;76&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">8&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;8 months&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">NLR &#8805;3&#46;76 was associated with higher mortality or amputation rates&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">Ouellet et al&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">61</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">2016<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">Incident patients on haemodialysis&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">&#8805;3&#46;9&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">36 months&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">NLR &#8805;3&#46;9 &#40;third tertile&#41; was associated with higher total mortality rates&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">Neuen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">58</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">2016<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">NLR&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">Incident patients on haemodialysis&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">&#8805;3&#46;3&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">37 months&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">NLR correlated positively with CRP and negatively related to Hb&#46; NLR was associated with higher total and cardiovascular mortality rates&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">Kato et al&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">62</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">2013<span class="elsevierStyleVsp" style="height:0.5px"></span>&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">Glasgow Prognostic Score &#40;standard and modified&#41;&#44; NLR&#44; PLR&#44; Prognostic Index and Prognostic Nutritional Index&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">Long-term haemodialysis&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">NLR &#8805;5PLR 150&#8211;300 and &#8805;300&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">42 months&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">All the markers &#40;including NLR and PLR&#41; were associated with higher total mortality rates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical studies of NLR&#47;PLR as predictors of death in patients with chronic kidney disease&#46;</p>"
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