CKD Staging-evolution not revolution
Read
11687
Timeswas read the article
2725
Total PDF
8962
Total HTML
Share statistics
array:21 [ "pii" => "X2013251410050739" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Jul.10501" "estado" => "S300" "fechaPublicacion" => "2010-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:493-500" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5547 "formatos" => array:3 [ "EPUB" => 305 "HTML" => 4472 "PDF" => 770 ] ] "Traduccion" => array:1 [ "en" => array:17 [ "pii" => "X0211699510050731" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2010.Jul.10501" "estado" => "S300" "fechaPublicacion" => "2010-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2010;30:493-500" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 8735 "formatos" => array:3 [ "EPUB" => 359 "HTML" => 7715 "PDF" => 661 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "CKD Staging-evolution not revolution" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "493" "paginaFinal" => "500" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C.G. Winearls, R. Haynes, R. Glassock" "autores" => array:3 [ 0 => array:2 [ "Iniciales" => "C.G." "apellidos" => "Winearls" ] 1 => array:2 [ "Iniciales" => "R." "apellidos" => "Haynes" ] 2 => array:2 [ "Iniciales" => "R." "apellidos" => "Glassock" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X2013251410050739" "doi" => "10.3265/Nefrologia.pre2010.Jul.10501" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050739?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050731?idApp=UINPBA000064" "url" => "/02116995/0000003000000005/v0_201502091425/X0211699510050731/v0_201502091425/en/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "X2013251410050720" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Jul.10526" "estado" => "S300" "fechaPublicacion" => "2010-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:501-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4938 "formatos" => array:3 [ "EPUB" => 265 "HTML" => 4007 "PDF" => 666 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Progress in understanding the pathogenesis of IgA nephropathy: New perspectives for the near future?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "501" "paginaFinal" => "507" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Avances en el conocimiento de la patogenia de la nefropatía IgA: ¿nuevas perspectivas para un futuro inmediato?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Segarra" "autores" => array:1 [ 0 => array:2 [ "Iniciales" => "A." "apellidos" => "Segarra" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X0211699510050723" "doi" => "10.3265/Nefrologia.pre2010.Jul.10526" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050723?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050720?idApp=UINPBA000064" "url" => "/20132514/0000003000000005/v0_201502091651/X2013251410050720/v0_201502091651/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "X2013251410050747" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Jul.10537" "estado" => "S300" "fechaPublicacion" => "2010-09-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:490-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 8444 "formatos" => array:3 [ "EPUB" => 294 "HTML" => 7319 "PDF" => 831 ] ] "en" => array:9 [ "idiomaDefecto" => true "titulo" => "Ultrasound-guided renal biopsy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "490" "paginaFinal" => "492" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Biopsia renal ecodirigida" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Rivera Gorrin" "autores" => array:1 [ 0 => array:2 [ "Iniciales" => "M." "apellidos" => "Rivera Gorrin" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X021169951005074X" "doi" => "10.3265/Nefrologia.pre2010.Jul.10537" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X021169951005074X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050747?idApp=UINPBA000064" "url" => "/20132514/0000003000000005/v0_201502091651/X2013251410050747/v0_201502091651/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "titulo" => "CKD Staging-evolution not revolution" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "493" "paginaFinal" => "500" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "C.G. Winearls, R. Haynes, R. Glassock" "autores" => array:3 [ 0 => array:4 [ "Iniciales" => "C.G." "apellidos" => "Winearls" "email" => array:1 [ 0 => "chris.winearls@orh.nhs.uk" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "R." "apellidos" => "Haynes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "R." "apellidos" => "Glassock" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Oxford Kidney Unit, Churchill Hospital, Headington, Oxford, UK, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "David Geffen School of Medicine, University of California, Los Angeles, USA, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10501_108_6117_en_10501_t1.jpg" "Alto" => 251 "Ancho" => 1053 "Tamanyo" => 38999 ] ] "descripcion" => array:1 [ "en" => "Stages of chronic kidney disease" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">The concept of generic chronic kidney disease (CKD) has been the «big idea» in nephrology in the last decade. It stimulated a surge of investigation and publications. It was a timely response to the concerns of both nephrologists and public health physicians that the demand for renal replacement therapy (RRT) for end-stage renal disease (ESRD) was increasing inexorably, contributing disproportionately to the inflation of health care spending; 2% of the UK NHS budget is spent on dialysis and transplantation for 0.01% of the population. Insufficient attention appeared to have been paid to the reservoir of patients feeding this pool. The description of this group of patients was moreover untidy and included the terms pre-dialysis, chronic renal failure, chronic renal insufficiency, chronic renal impairment, pre-uraemia and even Bright’s disease before renal biopsy. Primary care physicians were largely uninformed about renal disease and naïve in their interpretation of serum creatinine measurements so they left the problem to the small number of specialists in renal units. Because renal disease is relatively silent in its early stages, diagnosis was often delayed and potential opportunities to prevent end-stage renal failure and treat its complications were lost. The Kidney Disease Outcomes Quality Initiative (KDOQI) produced its seminal work in 2002 describing a definition and a staging system (table 1) using a metric, estimated GFR (eGFR)<span class="elsevierStyleSup">1</span>. This metric was first described in 1999<span class="elsevierStyleSup">2</span>, but used for several prior decades in another form, estimated creatinine clearance (eCcr)<span class="elsevierStyleSup">3</span>. Both estimates relied on equations using serum creatinine concentrations.</p><p class="elsevierStylePara">This transformation was warmly welcomed and widely adopted. It promoted awareness, research and policy initiatives designed to contain the problem of CKD. All this was laudable but the «big idea» has passed a «tipping point» and needs to be re-evaluated and refined<span class="elsevierStyleSup">4</span>. It has become a «brand» with slogans and references to frightening (but non-existent) epidemics and tsunamis, competing for prominence with many other health issues such as cancer, obesity, depression and diabetes all stridently demanding attention and funding because 1 in 10 or 1 in 5 or 1 in 3 of our citizens was or was destined to suffer from a condition which was avoidable or treatable. Nephrology opened its bidding at 1 in 10 and has raised it to 1 in 7 US citizens having CKD<span class="elsevierStyleSup">5,6</span>. It has been exploited commercially and medicalised large numbers of older citizens who have nothing to fear from a reduced eGFR. It is now time to pause, examine the relevant facts beyond the «hype» and give nephrology and public health more precise and useful tools. It is a «given» that good system design should solve problems without creating new ones.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">THE COMMON MISCONCEPTIONS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">There is an epidemic of CKD</span></p><p class="elsevierStylePara">The number of patients on RRT is indeed rising but there are good reasons for this other than an increased incidence of pre-RRT CKD in the population. Indeed the annual incidence of new RRT patients is plateauing in the developed world, for example the United Kingdom (figure 1)<span class="elsevierStyleSup">7</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Demographics are changing</span></span></p><p class="elsevierStylePara">The proportion of older people is increasing. In 1971 16% of the British population was over 65 years old; in 2004 the proportion had increased to over 18%. As ESRD is largely a disease of old age, the ageing population brings with it an increase in the number of people with ESRD.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Access to RRT is improving</span></span></p><p class="elsevierStylePara">When RRT (specifically dialysis) was first introduced the selection criteria were strict and it was essentially «rationed». Over the past few decades previous «contraindications» to RRT (e.g. diabetes or older age) have been abolished in high-income countries and consequently more people are eligible for RRT. One consequence of this is an increase in the burden of co-morbidity in the RRT population<span class="elsevierStyleSup">8</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Outcomes for RRT patients are improving</span></span><span class="elsevierStyleItalic"> </span></p><p class="elsevierStylePara">There has been a steady improvement in the survival of patients in high-income countries on RRT<span class="elsevierStyleSup">9-11</span>. This has been in excess of the improvement in life expectancy in the general population, although the reason for such improvement is undoubtedly multifactorial<span class="elsevierStyleSup">12</span>. This increased survival increases the size of the prevalent RRT population.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Dialysis is being started earlier</span></span></p><p class="elsevierStylePara">In the UK  the mean eGFR at start has increased from ~ 6 mL/min/1.73m<span class="elsevierStyleSup">2</span> to 8.5 mL/min/1.73m<span class="elsevierStyleSup">2</span> over the last ten years<span class="elsevierStyleSup">7</span>. Increased availability of RRT and increasing comorbidity of the RRT population have both contributed to this trend, as has a desire to avoid uraemic complications.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">The proportion of CKD patients who progress to treated ESRD is extremely small</span></span></p><p class="elsevierStylePara">In the UK the ratio of prevalent CKD:treated ESRD is 1:100 and to incident treated ESRD is 1:1,000. It is worth noting that the prevalence of CKD using the current definitions is similar in diverse populations but the incidence of treated ESRD is not. This implies that there are populations in whom the risk of progressing is much higher. The USA is a good example: the incidence of treated ESRD is 2-2.5 times that of most European countries which report a similar prevalence of «CKD». The problem of CKD as defined is therefore not primarily about ESRD. There has to be a better way of identifying subjects at risk of needing treatment for ESRD: trawling by eGFR is using too fine a net.</p><p class="elsevierStylePara">There is nevertheless no room for complacency. ESRD limits length and quality of life and its treatment is expensive so attempts to delay or prevent it should be made. There may well be a major problem in the future if the prevalence of diabetes continues to rise (in combination with the ageing population) and renal complications are not prevented, but this has not yet been observed.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The construct will reduce late referral of ESRD patients</span></p><p class="elsevierStylePara">Late referral of patients to renal services for RRT is defined as contact less than 90 days before RRT is needed.  These patients have worse outcomes<span class="elsevierStyleSup">13</span>. They cannot consider and choose their modality, are usually started on haemodialysis via a central catheter, take longer to establish on treatment, spend longer in hospital and have more advanced complications of renal failure. They have a higher mortality than those referred earlier but are more often in high risk groups with much co-morbidity.  The commonly quoted estimates are that around one quarter of new starters are «late referrals». Recently Udayaraj et al. audited this in Oxford<span class="elsevierStyleSup">14</span>. It emerged that only 4% of new starters were avoidable late referrals (figure 2). The remainder had acute presentations of unpredictable disorders that cause irreversible renal failure or were migrants or refugees who were not in the NHS system previously. Moreover the true late referrals should have been identified from their abnormal serum creatinine and known diagnoses.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The construct identifies patients with treatable complications</span></p><p class="elsevierStylePara">Moranne et al. have surveyed the prevalence of complications of CKD<span class="elsevierStyleSup">15</span> (figure 3).  It is apparent that complications (which are quite sensitively defined) are infrequent in the early stages of CKD and only become obvious when the GFR is <30 mL/min. Such patients are just as easily identified by their abnormal serum creatinine interpreted in context as by eGFR.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The CKD construct identifies a separate group of patients at risk of cardiovascular disease requiring treatment</span></p><p class="elsevierStylePara">The commonest cause of death in patients with CKD is cardiovascular disease and the risk of cardiovascular events in inversely proportional to the GFR such that a 20 mL/min/1.73m<span class="elsevierStyleSup">2</span> lower eGFR is associated with a 50% increased risk of a cardiovascular event (and a 40% increased risk of mortality)<span class="elsevierStyleSup">16</span> (a finding recently confirmed by a collaborative meta-analysis)<span class="elsevierStyleSup">17</span>. Many traditional cardiovascular risk factors (e.g. blood pressure and LDL cholesterol) have a continuous association with risk even within the «normal» range. It would be surprising if a condition which increased blood pressure (and to a lesser extent produced dyslipidaemia) were not associated with an increased risk of cardiovascular disease<span class="elsevierStyleSup">18</span>. However, because eGFR may be a risk marker does not make lower values a «disease»<span class="elsevierStyleSup">19</span>. </p><p class="elsevierStylePara">Additionally, most patients with CKD will already have established cardiovascular risk factors (e.g. age, hypertension, diabetes) and therefore have an indication for appropriate preventative treatments (e.g. blood pressure- and lipid-lowering therapy), so the presence of CKD does not alter management. Furthermore, as high blood pressure is one of the major contributors to the progression of CKD, CKD is an indication for strict blood pressure control regardless of the cardiovascular risk association.</p><p class="elsevierStylePara">An additional complication is that patients with advanced CKD develop an atypical form of vascular disease, more akin to the heart failure population than the general population in which atherosclerotic disease dominates. There is considerable uncertainty about which treatments can effectively (and safely) reduce cardiovascular risk in these patients. The Study of Heart and Renal Protection (SHARP) will provide some clarity about the role of LDL cholesterol reduction when it reports in late 2010<span class="elsevierStyleSup">20</span>. Until then, the presence of CKD does not alter management due to the lack of therapeutic options. For CKD to be a useful concept, it requires more than an unsurprising association with cardiovascular disease.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">THE FLAWS IN THE CONCEPT</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CKD is not homogeneous</span></p><p class="elsevierStylePara">CKD is presented as an homogeneous syndrome of progressive renal injury and functional impairment causing an increase risk of premature death, adverse cardiovascular events, complications of kidney failure and end-stage renal failure all in proportion to the GFR. Curiously for a continuum, the stages are divided by «bins» of GFR: >90; 60-89; 30-59; 15-29 and <15. These subdivisions are arbitrary and are not predictive of consequences.</p><p class="elsevierStylePara">It ignores the context of the kidney functional impairment, mixing subjects with a kidney disease with those with chronic disease that impinges on kidney function. Thus the majority of those held to have CKD have no identifiable kidney disease. This distinction is important because those with primary kidney disease behave differently from those that have secondary kidney dysfunction. A patient with congestive heart failure with an eGFR of 25 mL/min/1.73m<span class="elsevierStyleSup">2</span> is in a different prognostic group from one with polycystic kidney disease and a similar eGFR.</p><p class="elsevierStylePara">This conflation of the two problems in the same schema explains why the prevalence of so-called CKD is so different from bona fide kidney disease. This has led El Nahas to propose the concept of C-K-D especially in the elderly as being «Cardio-Kidney-Damage» reflecting the interaction of atherosclerosis, cardiovascular disease, kidney damage and dysfunction<span class="elsevierStyleSup">21</span>. To describe such patients as having chronic kidney disease is to put all the emphasis on one organ. It is no surprise that these patients die of their vascular disease and not of kidney failure for they are more likely to be diabetic, hypertensive, suffer heart failure and have had strokes and myocardial infarcts<span class="elsevierStyleSup">22</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The purpose of the system</span></p><p class="elsevierStylePara">It claims to stage kidney disease but it only divides GFRs into «bins».  It is used clinically in individual patients and in populations as a risk stratification tool. Disease staging and risk stratification should be separated, have different end points and different purposes. For example<span class="elsevierStyleSup">23</span> a subject with an eGFR of 45 mL/min/1.73m<span class="elsevierStyleSup">2</span> is at double the risk of acute kidney injury after major surgery than one with a GFR of >60 mL/min/1.7 3m<span class="elsevierStyleSup">2</span>. The absolute risk –though greater– is still very small. This is not a justification for labelling the subject at risk as having a disease<span class="elsevierStyleSup">19</span>. The staging system is being used to predict risk of a wide variety of illnesses including pneumonia, hospitalisation and fractures and the relationship being used to justify the label «disease». Subjects with co-morbidity are at risk of adverse events and have lower eGFRs and therefore worse stages of CKD. These associations are therefore a result of «reverse causality» rather than CKD directly causing the poor outcome. In contrast, staging of a disease is about the prognosis of that disease and is usually ordinal and multi-dimensional and determines subsequent treatment.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The design of the system</span></p><p class="elsevierStylePara">It is strange that the staging system makes no reference to the cause of CKD. Cancer staging systems are specific to the tumour site and the implications of the different stages have very different implications based on the type of cancer concerned (e.g. some metastatic cancers are treatable whereas others currently have no therapeutic options). In this manner, the CKD «staging» system is more akin to the grade of a tumour (i.e. a measure of its degree of dysplasia) which is only one piece of useful information about a tumour (whereas the CKD staging system is being used as a single defining description of the kidney problem).</p><p class="elsevierStylePara">The underlying diagnosis is obviously critical to the subsequent management of the kidney problem. Although some treatments are universal (e.g. strict blood pressure control), others (e.g. immunosuppression) are only useful patients with specific disorders diagnosed by renal biopsy e.g. membranous nephropathy or systemic lupus erythematosus.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The normal range of GFR is wrong</span></p><p class="elsevierStylePara">For a schema that is so rigidly dependent on GFR it is extraordinary that the normal range is held to be >90 mL/min/1.73m<span class="elsevierStyleSup">2</span> across all age ranges and 60-89 mL/min/1.73m<span class="elsevierStyleSup">2</span> is considered «reduced». This conflicts with measured GFRs in kidney donors and ignores the observed reduction in GFR with age<span class="elsevierStyleSup">24</span>. The rigidity also ignores the biological variation between individuals and the fact that GFR is not constant in an individual. The change in GFR after a high protein meal, in pregnancy and after kidney donation demonstrate clearly that humans have reserve and gear their GFR to their needs.</p><p class="elsevierStylePara">The problem has been aggravated by the imprecision and bias of eGFR at the upper ranges and has caused confusion especially when it was realised, after eGFR was rolled out, that the method of creatinine measurement was rather important. Quite small differences had huge effects on eGFRs and therefore on estimates of the prevalence of CKD. We are now being offered the CKD-EPI equation which reduces the bias of the estimates but does not improve precision very much compared to the eGFR (MDRD) equation<span class="elsevierStyleSup">25</span>. We may yet move on to combine the creatinine-based equations (CKD-EPI and MDRD) with cystatin C to improve specificity, but cystatin C may not be much superior to creatinine<span class="elsevierStyleSup">26</span>. It is not surprising that colleagues in primary care are confused and irritated. Having informed patients they have CKD they now have to say that a different method of evaluating the same blood test reveals the original diagnosis to have been wrong.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">It does not include proteinuria in stages 3-5</span></span></p><p class="elsevierStylePara">The importance of proteinuria, especially macro-proteinuria (overt proteinuria), in informing prognosis has emerged strongly from recent studies<span class="elsevierStyleSup">22</span>. Indeed proteinuria is a worse prognostic factor than reduced GFR alone and there is synergy between them. Proteinuria (albuminuria) has a continuous positive association with risk, while eGFR in non-linearly related to risk of adverse outcomes. It will therefore be impossible to stage kidney disease 1-5 in a unidimensional manner with two different variables. This problem is neatly illustrated in the PREVEND Study which showed that normo-albuminuric CKD stage 3 had a better prognosis than stage 1 with micro-albuminuria<span class="elsevierStyleSup">27</span>. A worse stage should not have a better prognosis.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">It is not calibrated for age</span></span></p><p class="elsevierStylePara">Using an absolute threshold level of eGFR (i.e. <60 mL/min/1.73m<span class="elsevierStyleSup">2</span>) alone to diagnose CKD (stage 3) without any modification for the effects of normal aging cannot, in our estimation, be justified<span class="elsevierStyleSup">28</span>. This is the main reason why «CKD» is so common in the elderly. Cross-sectional studies of eGFR with aging have uniformly and consistently shown a systematic decline in eGFR (and measured GFR) with aging (averaging about 7-10 mL/min/1.73m<span class="elsevierStyleSup">2</span> per decade, beginning after age 30-40 years)<span class="elsevierStyleSup">24</span>. Longitudinal studies in the same subjects over extended periods of time are sparse and suggested that such declines in eGFR are the general rule<span class="elsevierStyleSup">29</span>. Any evidence that such a modest decline in eGFR associated with normal aging in the absence of any structural disease or proteinuria confers any survival disadvantage has not yet appeared.  No prospective trials designed to curtail the age-associated decline in eGFR in order to determine an effect on outcome have been conducted. The decline in eGFR with aging is not connected to elevation in blood pressure nor to underlying renal morphology.<span class="elsevierStyleSup">30,31</span>  To arbitrarily select a single absolute threshold of eGFR (one that is 50% of a level in a 20 year old adult) to define CKD is simply inappropriate and incorrect. For example an eGFR of 50 mL/min/1.73m<span class="elsevierStyleSup">2</span> has radically different implications in a 25 year old man (unequivocally abnormal for age) and a 75 year old female (within the normal range for age), leading some to call for age- (and gender-) specific eGFR values<span class="elsevierStyleSup">32</span><span class="elsevierStyleInf">.</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Micro-albuminuria alone is diagnostic of CKD</span></span></p><p class="elsevierStylePara">It is noteworthy that the prevalence of Stage 1 and 2 CKD is largely determined by the presence of microalbuminuria  (urinary albumin to creatinine ratio of 3 – 30 mg/mmol).  In fact, according to the often quoted NHANES study, over 90% of subjects with stages 1 and 2 CKD respectively had only microalbuminuria as the diagnostic criterion<span class="elsevierStyleSup">6</span>. Microalbuminuria is well known to by a very dynamic condition influenced by non-specific events such as fever, exercise, obesity, ageing, medications, remote infection and inflammation. This was elegantly demonstrated in a subsample of the NHANES dataset in which only 50% of people with eGFR >90 mL/min/1.73m<span class="elsevierStyleSup">2</span> and microalbuminuria at their first visit had persistent microalbuminuria at a follow-up visit about two weeks later<span class="elsevierStyleSup">5</span><span class="elsevierStyleInf">.</span>  Elevated urinary excretion rates of albumin are strongly associated with cardiovascular disease perhaps because atheromatous plaques engender an inflammatory state or because of systemic endothelial dysfunction<span class="elsevierStyleSup">33</span><span class="elsevierStyleInf">.</span><span class="elsevierStyleSup"> </span>One might question whether microalbuminuria alone without any other manifestation of <span class="elsevierStyleItalic">kidney</span> damage should qualify as a diagnostic criterion for CKD.  Microalbuminuria may not even be a very reliable predictor of progression of kidney disease in diabetes<span class="elsevierStyleSup">34</span><span class="elsevierStyleInf">.</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">PROPOSALS FOR REDESIGN OF THE CONCEPT</span></p><p class="elsevierStylePara">Nephrologists and others have responded to these defects and proposed alternatives.<span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">UK National Institute for Clinical Excellence (NICE)</span></p><p class="elsevierStylePara">The key changes in the NICE construct from KDOQI are the requirement for macroproteinuria (overt proteinuria) in CKD stages 1 and 2 (microalbuminuria is disqualified as a sole indicator of CKD), the splitting of CKD stage 3 into an A and B substage at an eGFR of 45 mL/min/1.73m<span class="elsevierStyleSup">2</span>, and the addition of the suffix P + or  P – to indicate the presence or absence of overt proteinuria. This is a significant advance but still a faulty compromise. It ignores the fact that eGFR cannot accurately predict true GFR in the range 60 – 120 mL/min/1.73m<span class="elsevierStyleSup">2</span> and so there is no real purpose in subdividing patients regarded as having normal renal function (which many do not) who have other evidence of CKD into two separate stages. CKD stages 1 and 2 are in reality inseparable. The CKD stage 3 A and B distinction in part acknowledges that older subjects with eGFRs of 45 – 59 mL/min/1.73m<span class="elsevierStyleSup">2</span> (especially if they have no abnormal proteinuria) are not at excess risk of renal failure, complications or cardiovascular events<span class="elsevierStyleSup">27</span>. However, this leaves subjects without any disease with a label of CKD stage 3A (half way to the end-point stage 5) which is a very unsatisfactory situation from a patients perspective. Sadly, even these sensible modifications have not been widely adopted in clinical practice or in community screening proposals.<span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Kaiser Permanente</span></p><p class="elsevierStylePara">Rutkowski <span class="elsevierStyleItalic">et al</span>. “departed” from the KDOQI system by requiring macroproteinuria for stages 1, 2 and 3 and adjusting GFR for those falling into stage 3 by adding half of the subject’s age (up to 85 years) to the GFR<span class="elsevierStyleSup">35</span><span class="elsevierStyleInf">.</span> Using these stiffer requirements for diagnosing CKD they found the prevalence of CKD in the population for which this HMO was responsible of  0.1%, 0.2%, 1.7%, 0.5% and 0.01% (for stages 1 to 5 [not on RRT] respectively). These are credible estimates for nephrologists and are one-fifth the values quoted by NHANES using the KDOQI criteria<span class="elsevierStyleSup">6</span><span class="elsevierStyleBold"> . </span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">The CARI Guidelines</span></p><p class="elsevierStylePara">The Caring for Australians with Renal Impairment (CARI) guidelines (currently under final development) diagnose CKD by the presence of either kidney damage (proteinuria, haematuria or structural abnormalities) or an eGFR <60 mL/min/1.73m<span class="elsevierStyleSup">2</span> and suggest that an underlying cause is then sought. They recommend that kidney disease is staged by eGFR (with stage 3 split into 3A and 3B as NICE above) and albuminuria (normal, micro- and macro-albuminuria) simultaneously. However, these guidelines acknowledge that in people aged over 70 years with a stable eGFR >45 mL/min/1.73m<span class="elsevierStyleSup">2</span> and albuminuria in the normal range, the reduced eGFR may be consistent with physiological age-related GFR decline.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Winearls and Glassock</span></p><p class="elsevierStylePara">We have proposed a system that requires that the subject have specific persisting, irreversible pathology of the kidneys (inferred from abnormal urine deposit, macro-proteinuria, abnormal kidney imaging or histology) and that the GFR be referenced to percentiles for age, gender and ethnicity4.  Additionally  the suffix P+ or P- should be used denoting whether the renal function is deteriorating (e.g. at >3 mL/min /1.73m2/year). If the same system was to be used for renal transplant recipients the suffix T could be used.</p><ul><li>Stage 1 CKD: the presence of kidney injury but an eGFR within the upper 95% of the age-specific range.</li><li>Stage 2 CKD: the presence of kidney injury with an eGFR  below the 5th centile for age but >30 mL/min/1.73m<span class="elsevierStyleSup">2</span> and no evidence of complications of reduced kidney function (i.e. anaemia attributable to CKD or mineral-bone disorder).</li><li>Stage 3 CKD: an eGFR below 5th centile for age with complications or an eGFR <30 mL/min/1.73m<span class="elsevierStyleSup">2</span> which is unequivocally abnormal in all age groups. Kidney injury could be inferred.</li><li>Stage 4 CKD: an eGFR of <15 mL/min/1.73m<span class="elsevierStyleSup">2</span> which is generally accepted as the point at which there is a significant risk to the health and life of the patient.</li><li>Stage 5 CKD: patients receiving renal replacement treatment by dialysis.</li></ul><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Patients with an eGFR >30 mL/min/1.73m<span class="elsevierStyleSup">2</span> but less than the 5th centile for age without any evidence of structural renal disease or complications could be described as having isolated “reduced (kidney) function of uncertain significance” or ReFUS. Like patients with monoclonal gammopathy of uncertain significant (MGUS) who are followed to ensure timely diagnosis of myeloma, such patients should be followed (in primary care) to ensure they do not subsequently develop “true” CKD.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">KDIGO (2009)</span></p><p class="elsevierStylePara">At the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference held in London in October 2009 an extensive meta-analysis of numerous studies examining prognosis of CKD recognised the importance of proteinuria, and the underlying diagnosis as well as GFR. The “grey area” remained CKD stage 3 especially the upper half of its range (45 – 59 mL/min/1.73m<span class="elsevierStyleSup">2</span>). There did not appear to be a clear disadvantage for older subjects (>65 years) in being in this category if there was no proteinuria. A descriptive system was proposed; patients would be classified by:</p><p class="elsevierStylePara">1.    Diagnosis (if known);</p><p class="elsevierStylePara">2.    eGFR stages  1 – 5 with stage 3 being subdivided at the 45 mL/min/1.73m<span class="elsevierStyleSup">2</span> point into stages 3A and 3B (similar to NICE and CARI, above);</p><p class="elsevierStylePara">3.    Albuminuria: A0 (none), A1 (microalbuminuria) and A2 (macroalbuminuria) using the spot first morning void urinary albumin to creatinine ratio as the standard of reference</p><p class="elsevierStylePara">The issue of age calibration of GFR was unresolved and no decision was reached as to what to do with stage 3A in older subjects was reached. This will be essential as they comprise most of CKD in the elderly.  The issue of whether isolated (persistent) microalbuminuria is indicative of chronic kidney disease was hotly debated without any satisfactory consensus.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">The nephrology community needs to insist that the architects of a new system for classifying CKD develop it in a transparent manner, accommodate legitimate criticism and provide an accurate, useful approach to the diagnosis, classification, staging and risk stratification of CKD.  The stratification of risk of adverse events (death, ESRD, acute kidney injury and CV disease) should be separate from the requirements for diagnosis.</p><p class="elsevierStylePara">The application and pitfalls of the new system at the “bedside” should be clearly articulated.  The needs of public health authorities and epidemiologists to identify CKD in terms of incidence and prevalence should be considered but not relegate the need for a clinical tool to identity bona fide CKD and its attendant risks to inferior status.  Increasing awareness of CKD is a logical by-product of a classification system but mislabelling large segments of a relatively healthy population as diseased based on innocuous laboratory findings combined with an overly rigid diagnosis and staging system should be avoided.</p><p class="elsevierStylePara"><a href="grande/10501_108_6117_en_10501_t1.jpg" class="elsevierStyleCrossRefs"><img src="10501_108_6117_en_10501_t1.jpg" alt="Stages of chronic kidney disease"></img></a></p><p class="elsevierStylePara">Table 1. Stages of chronic kidney disease</p><p class="elsevierStylePara"><a href="grande/10501_108_6118_en_10501_f1_copy1.jpg" class="elsevierStyleCrossRefs"><img src="10501_108_6118_en_10501_f1_copy1.jpg" alt="RRT incidence rates in the countries of the United Kingdom 1990-2008 "></img></a></p><p class="elsevierStylePara">Figure 1. RRT incidence rates in the countries of the United Kingdom 1990-2008 </p><p class="elsevierStylePara"><a href="grande/10501_108_6119_en_10501_f2.jpg" class="elsevierStyleCrossRefs"><img src="10501_108_6119_en_10501_f2.jpg" alt="Referrals to the Oxford Kidney Unit between 2000 and 2008 according to the time between presentation to the unit and start date of RRT. Only 4% of referrals were avoidable late referrals"></img></a></p><p class="elsevierStylePara">Figure 2. Referrals to the Oxford Kidney Unit between 2000 and 2008 according to the time between presentation to the unit and start date of RRT. Only 4% of referrals were avoidable late referrals</p><p class="elsevierStylePara"><a href="grande/10501_108_6120_en_10501_f3.jpg" class="elsevierStyleCrossRefs"><img src="10501_108_6120_en_10501_f3.jpg" alt="Prevalence of metabolic complications according to GFR"></img></a></p><p class="elsevierStylePara">Figure 3. Prevalence of metabolic complications according to GFR</p>" "pdfFichero" => "P1-E503-S2282-A10501-EN.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec441588" "palabras" => array:1 [ 0 => "Estimated Glomerular Filtration Rate" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec441590" "palabras" => array:1 [ 0 => "Staging" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec441592" "palabras" => array:1 [ 0 => "eGFR" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec441594" "palabras" => array:1 [ 0 => "Chronic Kidney Disease" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10501_108_6117_en_10501_t1.jpg" "Alto" => 251 "Ancho" => 1053 "Tamanyo" => 38999 ] ] "descripcion" => array:1 [ "en" => "Stages of chronic kidney disease" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10501_108_6118_en_10501_f1_copy1.jpg" "Alto" => 436 "Ancho" => 511 "Tamanyo" => 31750 ] ] "descripcion" => array:1 [ "en" => "RRT incidence rates in the countries of the United Kingdom 1990-2008" ] ] 2 => array:8 [ "identificador" => "fig3" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10501_108_6119_en_10501_f2.jpg" "Alto" => 375 "Ancho" => 511 "Tamanyo" => 22284 ] ] "descripcion" => array:1 [ "en" => "Referrals to the Oxford Kidney Unit between 2000 and 2008 according to the time between presentation to the unit and start date of RRT. Only 4% of referrals were avoidable late referrals" ] ] 3 => array:8 [ "identificador" => "fig4" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10501_108_6120_en_10501_f3.jpg" "Alto" => 543 "Ancho" => 1049 "Tamanyo" => 56980 ] ] "descripcion" => array:1 [ "en" => "Prevalence of metabolic complications according to GFR" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11904577" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "2.\u{A0}Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "3.\u{A0}Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. <a href="http://www.ncbi.nlm.nih.gov/pubmed/1244564" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "4.\u{A0}Winearls CG, Glassock RJ. Dissecting and refining the staging of chronic kidney disease. Kidney Int 2009;75:1009-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19242501" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "5.\u{A0}Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41:1-12. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12500213" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "6.\u{A0}Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038-47. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17986697" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "7.\u{A0}Farrington K, Udayaraj U, Gilg J, Feehally J. UK Renal Registry 11th Annual Report (December 2008): Chapter 3 ESRD incident rates in 2007 in the UK: national and centre-specific analyses. Nephron Clin Pract 2009;111 Suppl 1:c13-41. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19542695" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "8.\u{A0}Udayaraj U, Tomson CR, Gilg J, Ansell D, Fogarty D. UK Renal Registry 11th Annual Report (December 2008): Chapter 6 Comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland: national and centre-specific analyses. Nephron Clin Pract 2009;111 Suppl 1:c97-111. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19542707" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "9.\u{A0}US Renal Data System. USRDS 2006 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2006." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "10.\u{A0}Ansell D, Roderick P, Hodsman A, Ford D, Steenkamp R, Tomson C. UK Renal Registry 11th Annual Report (December 2008): Chapter 7. Survival and causes of death of UK adult patients on renal replacement therapy in 2007: national and centre-specific analyses. Nephron Clin Pract 2009;111 (Suppl 1):c113-39. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19542694" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "11.\u{A0}Ansell D, Feehally J, Fogarty D, Tomson C, Williams AJ, Warwick G. UK Renal Registry Report. Bristol, UK: UK Renal Registry; 2008." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "12.\u{A0}\u{A0}\u{A0}\u{A0}\u{A0} Jassal SV, Trpeski L, Zhu N, Fenton S, Hemmelgarn B. Changes in survival among elderly patients initiating dialysis from 1990 to 1999. CMAJ 2007;177:1033-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17954892" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "13.\u{A0}Huisman RM. The deadly risk of late referral. Nephrol Dial Transplant 2004;19:2175-80. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15299096" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "14.\u{A0}Udayaraj U, Haynes R, Winearls CG. Late presentation of patients with ESRD for RRT is avoidable in the minority. In: UK Renal Association; 2010; Manchester, UK; 2010." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "15.\u{A0}Moranne O, Froissart M, Rossert J, et al. Timing of onset of CKD-related metabolic complications. J Am Soc Nephrol 2009;20:164-71. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19005010" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "16.\u{A0}Mafham M, Emberson J, Landray M, Baigent C. Meta-Analysis of Observational Studies Relating Estimated Glomerular Filtration Rate to Risk of Death or Major Cardiovascular Events. J Am Soc Nephrol 2006;17:193A." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Chronic Kidney Disease Prognosis Consortium. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010; 375: 2073-81. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20483451" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "18.\u{A0}Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet 2000;356:147-52. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10963260" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "19.\u{A0}Clase CM, Garg AX, Kiberd BA. Classifying kidney problems: can we avoid framing risks as diseases? BMJ 2004;329:912-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15485978" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "20.\u{A0}Baigent C, Landray M. Study of Heart and Renal Protection (SHARP). Kidney Int Suppl 2003:S207-10." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "21.\u{A0}El Nahas M. Cardio-Kidney-Damage: a unifying concept. Kidney Int 2010;78:14-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20445499" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "22.\u{A0}Hemmelgarn BR, Manns BJ, Lloyd A, et al. Relation between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20124537" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "23.\u{A0}Hsu CY, Ordonez JD, Chertow GM, Fan D, McCulloch CE, Go AS. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18385668" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "24.\u{A0}Wetzels JFM, Kiemeney LALM, Swinkels DW, Willems HL, Heijer Md. Age- and gender-specific reference values of estimated GFR in Caucasians: The Nijmegen Biomedical Study. Kidney Int 2007;72:632-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17568781" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "25.\u{A0}Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19414839" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "26.\u{A0}Stevens LA, Schmid CH, Greene T, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int 2009;75:652-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19119287" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "27.\u{A0}Brantsma AH, Bakker SJ, Hillege HL, De Zeeuw D, De Jong PE, Gansevoort RT. Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion. Nephrol Dial Transplant 2008;23:3851-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18641082" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "28.\u{A0}Glassock RJ, Winearls C. Ageing and the glomerular filtration rate: truths and consequences. Trans Am Clin Climatol Assoc 2009;120:419-28. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19768194" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "29.\u{A0}Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278-85. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3989190" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "30.\u{A0}Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol 1976;31:155-63. <a href="http://www.ncbi.nlm.nih.gov/pubmed/1249404" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "31.\u{A0}Rule AD, Amer H, Cornell LD, et al. The Association Between Age and Nephrosclerosis on Renal Biopsy Among Healthy Adults. Ann Intern Med 2010;152:561-7." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "32.\u{A0}Poggio ED, Rule AD. Can we do better than a single estimated GFR threshold when screening for chronic kidney disease? Kidney Int 2007;72:534-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17713563" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "33.\u{A0}Hillege HL, Janssen WM, Bak AA, et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001;249:519-26. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11422658" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "34.\u{A0}Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of Microalbuminuria in Type 1 Diabetes. N Engl J Med 2003;348:2285-93. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12788992" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 34 => array:3 [ "identificador" => "bib35" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "35.\u{A0}Rutkowski M, Mann W, Derose S, et al. Implementing KDOQI CKD Definition and Staging Guidelines in Southern California Kaiser Permanente. Am J Kidney Dise 2009;53:S86-S99." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003000000005/v0_201502091651/X2013251410050739/v0_201502091651/en/main.assets" "Apartado" => array:4 [ "identificador" => "35446" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special Originals" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003000000005/v0_201502091651/X2013251410050739/v0_201502091651/en/P1-E503-S2282-A10501-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050739?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 7 | 16 |
| 2024 October | 53 | 49 | 102 |
| 2024 September | 69 | 40 | 109 |
| 2024 August | 72 | 89 | 161 |
| 2024 July | 46 | 31 | 77 |
| 2024 June | 73 | 61 | 134 |
| 2024 May | 60 | 46 | 106 |
| 2024 April | 70 | 38 | 108 |
| 2024 March | 55 | 25 | 80 |
| 2024 February | 52 | 35 | 87 |
| 2024 January | 53 | 30 | 83 |
| 2023 December | 33 | 24 | 57 |
| 2023 November | 54 | 45 | 99 |
| 2023 October | 55 | 49 | 104 |
| 2023 September | 51 | 28 | 79 |
| 2023 August | 47 | 32 | 79 |
| 2023 July | 61 | 35 | 96 |
| 2023 June | 58 | 28 | 86 |
| 2023 May | 57 | 36 | 93 |
| 2023 April | 56 | 17 | 73 |
| 2023 March | 64 | 33 | 97 |
| 2023 February | 64 | 18 | 82 |
| 2023 January | 76 | 28 | 104 |
| 2022 December | 79 | 32 | 111 |
| 2022 November | 75 | 43 | 118 |
| 2022 October | 58 | 44 | 102 |
| 2022 September | 59 | 32 | 91 |
| 2022 August | 59 | 47 | 106 |
| 2022 July | 61 | 48 | 109 |
| 2022 June | 60 | 29 | 89 |
| 2022 May | 101 | 34 | 135 |
| 2022 April | 121 | 55 | 176 |
| 2022 March | 173 | 60 | 233 |
| 2022 February | 162 | 47 | 209 |
| 2022 January | 76 | 33 | 109 |
| 2021 December | 89 | 43 | 132 |
| 2021 November | 64 | 35 | 99 |
| 2021 October | 123 | 49 | 172 |
| 2021 September | 111 | 41 | 152 |
| 2021 August | 81 | 45 | 126 |
| 2021 July | 72 | 39 | 111 |
| 2021 June | 55 | 26 | 81 |
| 2021 May | 105 | 44 | 149 |
| 2021 April | 185 | 50 | 235 |
| 2021 March | 190 | 35 | 225 |
| 2021 February | 197 | 30 | 227 |
| 2021 January | 127 | 26 | 153 |
| 2020 December | 121 | 12 | 133 |
| 2020 November | 90 | 17 | 107 |
| 2020 October | 56 | 22 | 78 |
| 2020 September | 50 | 9 | 59 |
| 2020 August | 51 | 16 | 67 |
| 2020 July | 65 | 19 | 84 |
| 2020 June | 51 | 8 | 59 |
| 2020 May | 53 | 19 | 72 |
| 2020 April | 75 | 22 | 97 |
| 2020 March | 67 | 12 | 79 |
| 2020 February | 76 | 19 | 95 |
| 2020 January | 60 | 16 | 76 |
| 2019 December | 78 | 26 | 104 |
| 2019 November | 62 | 18 | 80 |
| 2019 October | 72 | 12 | 84 |
| 2019 September | 91 | 15 | 106 |
| 2019 August | 81 | 24 | 105 |
| 2019 July | 80 | 19 | 99 |
| 2019 June | 92 | 27 | 119 |
| 2019 May | 68 | 15 | 83 |
| 2019 April | 165 | 32 | 197 |
| 2019 March | 85 | 29 | 114 |
| 2019 February | 52 | 17 | 69 |
| 2019 January | 48 | 20 | 68 |
| 2018 December | 86 | 29 | 115 |
| 2018 November | 104 | 20 | 124 |
| 2018 October | 98 | 24 | 122 |
| 2018 September | 82 | 21 | 103 |
| 2018 August | 52 | 13 | 65 |
| 2018 July | 38 | 6 | 44 |
| 2018 June | 43 | 11 | 54 |
| 2018 May | 46 | 14 | 60 |
| 2018 April | 41 | 5 | 46 |
| 2018 March | 58 | 10 | 68 |
| 2018 February | 57 | 5 | 62 |
| 2018 January | 43 | 9 | 52 |
| 2017 December | 65 | 12 | 77 |
| 2017 November | 47 | 7 | 54 |
| 2017 October | 45 | 16 | 61 |
| 2017 September | 44 | 13 | 57 |
| 2017 August | 30 | 28 | 58 |
| 2017 July | 38 | 27 | 65 |
| 2017 June | 40 | 20 | 60 |
| 2017 May | 70 | 27 | 97 |
| 2017 April | 42 | 32 | 74 |
| 2017 March | 34 | 34 | 68 |
| 2017 February | 92 | 25 | 117 |
| 2017 January | 38 | 22 | 60 |
| 2016 December | 74 | 10 | 84 |
| 2016 November | 72 | 15 | 87 |
| 2016 October | 142 | 12 | 154 |
| 2016 September | 182 | 8 | 190 |
| 2016 August | 177 | 6 | 183 |
| 2016 July | 148 | 8 | 156 |
| 2016 June | 136 | 0 | 136 |
| 2016 May | 158 | 0 | 158 |
| 2016 April | 100 | 0 | 100 |
| 2016 March | 94 | 0 | 94 |
| 2016 February | 105 | 0 | 105 |
| 2016 January | 124 | 0 | 124 |
| 2015 December | 100 | 0 | 100 |
| 2015 November | 86 | 0 | 86 |
| 2015 October | 85 | 0 | 85 |
| 2015 September | 82 | 0 | 82 |
| 2015 August | 66 | 0 | 66 |
| 2015 July | 57 | 0 | 57 |
| 2015 June | 25 | 0 | 25 |
| 2015 May | 48 | 0 | 48 |
| 2015 April | 8 | 0 | 8 |
Show all
