Definition and Classification of CKD: The Debate Should Be About Patient Prognosis—A Position Statement From KDOQI and KDIGO

Abstract

In 2002 the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) published a guideline on chronic kidney disease (CKD) covering evaluation, classification, and stratification of risk.1National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar The workgroup developing this guideline provided a new conceptual framework for a diagnosis of CKD independent of cause, and developed a classification scheme of kidney disease severity based on the level of glomerular filtration rate (GFR). Before this new system for defining and staging CKD was developed, vague and variable terminology, such as “chronic renal failure,” “chronic renal insufficiency,” “pre-dialysis,” and “pre-end-stage renal disease” prevented the use of a common and precise language.2Eknoyan G. Chronic kidney disease definition and classification: The quest for refinements.Kidney Int. 2007; 72: 1183-1185Crossref PubMed Scopus (29) Google Scholar The new system also represented a significant conceptual change, since kidney disease historically had been categorized mainly by cause. The definition is based on 3 components: (1) an anatomical or structural component (markers of kidney damage, including albuminuria), (2) a functional component (based on GFR), and (3) a temporal component (at least 3 months' duration of structural and/or functional alterations). The diagnosis of CKD relies on markers of kidney damage and/or a reduction in GFR. Stages 1 and 2 define conditions of kidney damage in the presence of a GFR of at least 90 mL/min/1.73 m2 or 60 to 89 mL/min/1.73 m2, respectively, and stages 3 to 5 define conditions of moderately and severely reduced GFR irrespective of markers of kidney damage (Table 1).Table 1Classification of CKD as Defined by KDOQI and Modified and Endorsed by KDIGOStageDescriptionClassification by SeverityClassification by Treatment1Kidney damage with normal or ↑ GFRGFR ≥ 90T if kidney transplant recipient2Kidney damage with mild ↓ in GFRGFR of 60-893Moderate ↓ in GFRGFR of 30-594Severe ↓ in GFRGFR of 15-295Kidney failureGFR < 15 (or dialysis)D if dialysisNote: GFR is given in mL/min/1.73 m2.Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; KDOQI, Kidney Disease Outcomes Quality Initiative. Open table in a new tab The impact that this classification system has had in only 6 years on the awareness of CKD in individuals and populations, on research activities, research support, and public health policy has been tremendous. There has been an exponential increase in the amount of research performed in patients with kidney disease not receiving long-term dialysis therapy since the guidelines were released, and the common definition of CKD has facilitated comparisons between studies. Thus, this new diagnostic classification of CKD has likely been one of the most profound conceptual developments in the history of nephrology.Nevertheless, there are limitations to this classification system, which is by its nature simple and necessarily arbitrary in terms of specifying the thresholds for definition and different stages. When the classification system was developed in 2002, the evidence base used for the development of this guideline was much smaller than the CKD evidence base today. It is the growth of this CKD database that has, ironically, stimulated recent discussions questioning the value of current CKD guidelines.Global Endorsement of a Common System for Definition and Staging of CKDIn 2004, KDIGO (Kidney Disease: Improving Global Outcomes), an independent not-for-profit foundation governed by an international Board of Directors with the stated mission of improving the care and outcomes of kidney disease patients worldwide, hosted its first Controversies Conference devoted to the definition and classification of CKD.3Levey A.S. Eckardt K.U. Tsukamoto Y. et al.Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2446) Google Scholar In preparation for this conference, a survey was sent to approximately 10,000 nephrologists worldwide via e-mail to assess their opinion of the KDOQI definition and classification of CKD. The responses to this survey provided a broad basis for the discussion. In 2006, KDIGO convened a second Controversies Conference to reanalyze the CKD classification and address questions of CKD screening and surveillance, public policy for CKD, and associations of CKD with cardiovascular disease, infections, and cancer.4Levey A.S. Atkins R. Coresh J. et al.Chronic kidney disease as a global public health problem: Approaches and initiatives–a position statement from Kidney Disease Improving Global Outcomes.Kidney Int. 2007; 72: 247-259Crossref PubMed Scopus (1022) Google Scholar After extensive discussion, participants of both conferences endorsed the global use of the definition and staging system for CKD originally developed by KDOQI. The only modification recommended at the 2004 conference was the addition of a classification for treatment by transplantation or dialysis, using the suffix “T” for all kidney transplant recipients at any level of GFR and “D” to indicate dialysis for CKD stage 5 patients treated by dialysis (Table 1).Both conferences acknowledged shortcomings of the current classification scheme and concluded that additional clinical information is required for the evaluation and management of individual cases of CKD. However, the potential benefits of adding information and granularity to the classification system was thought to be outweighed by added complexity that would limit its applicability, in particular to disciplines outside of nephrology.4Levey A.S. Atkins R. Coresh J. et al.Chronic kidney disease as a global public health problem: Approaches and initiatives–a position statement from Kidney Disease Improving Global Outcomes.Kidney Int. 2007; 72: 247-259Crossref PubMed Scopus (1022) Google Scholar Importantly, both conferences also defined research and public policy recommendations, several of which have subsequently been successfully addressed.3Levey A.S. Eckardt K.U. Tsukamoto Y. et al.Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2446) Google Scholar, 4Levey A.S. Atkins R. Coresh J. et al.Chronic kidney disease as a global public health problem: Approaches and initiatives–a position statement from Kidney Disease Improving Global Outcomes.Kidney Int. 2007; 72: 247-259Crossref PubMed Scopus (1022) Google ScholarDiscussion About the Need for RevisionRecently, discussions on the limitations of the current system for the definition and classification of CKD, and the benefits and disadvantages of a possible modification to this system, have led to a passionate debate primarily in the editorial and correspondence pages of nephrology subspecialty journals and in public forums.5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar, 6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 8Glassock R.J. Winearls C. Routine reporting of estimated glomerular filtration rate: Not ready for prime time.Nat Clin Pract Nephrol. 2008; 4: 422-423Crossref PubMed Scopus (21) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 10Glassock R.J. Winearls C. CKD—fiction not fact.Nephrol Dial Transplant. 2008; 23: 2695-2696Crossref PubMed Scopus (16) Google Scholar, 11de Jong P.E. Gansevoort R.T. Fact or fiction of the epidemic of chronic kidney disease–let us not squabble about estimated GFR only, but also focus on albuminuria.Nephrol Dial Transplant. 2008; 23: 1092-1095Crossref PubMed Scopus (42) Google Scholar, 12de Jong P.E. Gansevoort R.T. Reply.Nephrol Dial Transplant. 2008; 23: 2698-2699Crossref Scopus (1) Google Scholar, 13Coresh J. Stevens L.A. Levey A.S. Chronic kidney disease is common: What do we do next?.Nephrol Dial Transplant. 2008; 23: 1122-1125Crossref PubMed Scopus (47) Google Scholar, 14Levey A.S. Stevens L.A. Coresh J. Reply.Nephrol Dial Transplant. 2008; 23: 2696-2697Crossref Scopus (1) Google Scholar, 15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar, 16Landray M.J. Haynes R.J. Commentary: Controversies in NICE guidance on chronic kidney disease.BMJ. 2008; 337: a1793Crossref PubMed Scopus (5) Google Scholar, 17Glassock R.J. Winearls C. El Nahas M. Chronic kidney disease in Taiwan.Lancet. 2008; 372: 1949-1950Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 18Stevens L.A. Coresh J. Levey A.S. CKD in the elderly–old questions and new challenges: World Kidney Day 2008.Am J Kidney Dis. 2008; 51: 353-357Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 19Glassock R.J. Winearls C. CKD in the elderly.Am J Kidney Dis. 2008; 52: 803Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 20Stevens L.A. Coresh J. Levey A.S. In reply to ‘CKD in the elderly’.Am J Kidney Dis. 2008; 52: 803-804Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The perceived limitations focus on several areas.First, proponents of a change in the current system are generally concerned that the application of the current system leads to over- and misdiagnosis of CKD and possible overuse of speciality resources.6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar, 16Landray M.J. Haynes R.J. Commentary: Controversies in NICE guidance on chronic kidney disease.BMJ. 2008; 337: a1793Crossref PubMed Scopus (5) Google Scholar, 17Glassock R.J. Winearls C. El Nahas M. Chronic kidney disease in Taiwan.Lancet. 2008; 372: 1949-1950Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 19Glassock R.J. Winearls C. CKD in the elderly.Am J Kidney Dis. 2008; 52: 803Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Moreover, reported CKD prevalence rates, based on the use of some, although usually not all, of the components of the current definition and classification system are considered to be too high in comparison to incidence rates for treated kidney failure (end-stage renal disease).6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 16Landray M.J. Haynes R.J. Commentary: Controversies in NICE guidance on chronic kidney disease.BMJ. 2008; 337: a1793Crossref PubMed Scopus (5) Google Scholar, 17Glassock R.J. Winearls C. El Nahas M. Chronic kidney disease in Taiwan.Lancet. 2008; 372: 1949-1950Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 19Glassock R.J. Winearls C. CKD in the elderly.Am J Kidney Dis. 2008; 52: 803Abstract Full Text Full Text PDF PubMed Scopus (11) Google ScholarSecond, there is discomfort with the terminology used to define kidney disease and its different stages. This issue revolves around the question of when and how to use the term “disease” and how to separate it from “pre-disease states” and “risk factors.”5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar, 6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 16Landray M.J. Haynes R.J. Commentary: Controversies in NICE guidance on chronic kidney disease.BMJ. 2008; 337: a1793Crossref PubMed Scopus (5) Google Scholar, 19Glassock R.J. Winearls C. CKD in the elderly.Am J Kidney Dis. 2008; 52: 803Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 21Eknoyan G. Kidney disease: Wherefore, whence and whereto?.Kidney Int. 2007; 71: 473-475Crossref PubMed Scopus (7) Google Scholar The use of the general term “chronic kidney disease”, without further specification across the entire spectrum of CKD, and without regard to etiology, has also been considered problematic.Third, there are methodological issues of concern, which include the use of estimated GFR (eGFR) computed from estimating equations, especially in the elderly and in diverse ethnic and racial populations, for the initial diagnosis and staging of CKD and for determining changes in kidney function over time.5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar, 6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 8Glassock R.J. Winearls C. Routine reporting of estimated glomerular filtration rate: Not ready for prime time.Nat Clin Pract Nephrol. 2008; 4: 422-423Crossref PubMed Scopus (21) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 22Froissart M. Rossert J. Jacquot C. Paillard M. Houillier P. Predictive performance of the modification of diet in renal disease and Cockroft-Gault equations for estimating renal function.J Am Soc Nephrol. 2005; 16: 763-773Crossref PubMed Scopus (702) Google Scholar, 23Xie D. Joffe M.M. Brunelli S.M. et al.A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease.Clin J Am Soc Nephrol. 2008; 3: 1332-1338Crossref PubMed Scopus (60) Google Scholar There are also uncertainties about the methodology and cut-off values to diagnose abnormal urinary albumin and protein excretion.3Levey A.S. Eckardt K.U. Tsukamoto Y. et al.Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2005; 67: 2089-2100Crossref PubMed Scopus (2446) Google ScholarFourth, the appropriateness of the definitions and threshold values for different stages of CKD has been questioned. Some argue that CKD stages 1 and 2 are not associated with sufficiently adverse outcomes to justify their labelling as a “disease,”5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar, 6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar while others point out that the cardiovascular event rate is equally increased in stage 1 and 2 CKD as in stage 3 CKD.11de Jong P.E. Gansevoort R.T. Fact or fiction of the epidemic of chronic kidney disease–let us not squabble about estimated GFR only, but also focus on albuminuria.Nephrol Dial Transplant. 2008; 23: 1092-1095Crossref PubMed Scopus (42) Google Scholar In addition, it has been argued that so-called microalbuminuria, which is sufficient to diagnose CKD stage 1 or 2 in the presence of a GFR above 60 mL/min/1.73 m2, is more a cardiovascular disease outcome risk factor rather than a kidney disease outcome risk factor and reflects vascular rather than kidney disease,6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar, 17Glassock R.J. Winearls C. El Nahas M. Chronic kidney disease in Taiwan.Lancet. 2008; 372: 1949-1950Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar but the lack of proof for this assumption has also been pointed out.5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar It also has been questioned whether a GFR below 60 mL/min/1.73 m2 alone, in the absence of other markers of kidney disease, is sufficient to define CKD,6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 10Glassock R.J. Winearls C. CKD—fiction not fact.Nephrol Dial Transplant. 2008; 23: 2695-2696Crossref PubMed Scopus (16) Google Scholar, 11de Jong P.E. Gansevoort R.T. Fact or fiction of the epidemic of chronic kidney disease–let us not squabble about estimated GFR only, but also focus on albuminuria.Nephrol Dial Transplant. 2008; 23: 1092-1095Crossref PubMed Scopus (42) Google Scholar, 24Poggio E.D. Rule A.D. Can we do better than single estimated GFR threshold when screening for chronic kidney disease?.Kidney Int. 2007; 72: 534-536Crossref PubMed Scopus (30) Google Scholar in particular since epidemiological studies show a high proportion of elderly individuals and women in the stage 3 category.7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 8Glassock R.J. Winearls C. Routine reporting of estimated glomerular filtration rate: Not ready for prime time.Nat Clin Pract Nephrol. 2008; 4: 422-423Crossref PubMed Scopus (21) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 10Glassock R.J. Winearls C. CKD—fiction not fact.Nephrol Dial Transplant. 2008; 23: 2695-2696Crossref PubMed Scopus (16) Google Scholar, 25Wetzels J.F. Kiemeney L.A. Swinkels D.W. Willems H.L. den Heijer M. Age- and gender-specific reference values of estimated GFR in Caucasians: The Nijmegen biomedical study.Kidney Int. 2007; 72: 632-637Crossref PubMed Scopus (278) Google ScholarNumerous suggested revisions to the classification system have been offered. These include elimination of stages 1 and 2,15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar collapsing stages 1 and 2 into a single stage,6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar the need for additional evidence of kidney damage in the presence of GFR levels greater than 30 mL/min/1.73 m2 as a prerequisite for having CKD,7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 11de Jong P.E. Gansevoort R.T. Fact or fiction of the epidemic of chronic kidney disease–let us not squabble about estimated GFR only, but also focus on albuminuria.Nephrol Dial Transplant. 2008; 23: 1092-1095Crossref PubMed Scopus (42) Google Scholar lowering the threshold GFR value for stage 3 from 60 to 45 mL/min/1.73 m2,9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar adding 2 subcategories to stage 3 CKD corresponding to GFR values of 45 to 59 and 30 to 44 mL/min/1.73 m2,26Crowe E. Halpin D. Stevens P. for Guideline Development Group: Early identification and management of chronic kidney disease: Summary of NICE guidance.BMJ. 2008; 337: a1530Crossref PubMed Scopus (139) Google Scholar introducing age- and sex-specific GFR reference values,6Glassock R.J. Winearls C. The global burden of chronic kidney disease: How valid are the estimates?.Nephron Clin Pract. 2008; 110: c39-c47Crossref PubMed Scopus (50) Google Scholar, 7Glassock R.J. Winearls C. Screening for CKD with eGFR: Doubts and dangers.Clin J Am Soc Nephrol. 2008; 3: 1563-1568Crossref PubMed Scopus (151) Google Scholar, 8Glassock R.J. Winearls C. Routine reporting of estimated glomerular filtration rate: Not ready for prime time.Nat Clin Pract Nephrol. 2008; 4: 422-423Crossref PubMed Scopus (21) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar, 10Glassock R.J. Winearls C. CKD—fiction not fact.Nephrol Dial Transplant. 2008; 23: 2695-2696Crossref PubMed Scopus (16) Google Scholar, 15Bauer C. Melamed M.L. Hostetter T.H. Staging of chronic kidney disease: Time for a course of correction.J Am Soc Nephrol. 2008; 19: 844-846Crossref PubMed Scopus (109) Google Scholar, 24Poggio E.D. Rule A.D. Can we do better than single estimated GFR threshold when screening for chronic kidney disease?.Kidney Int. 2007; 72: 534-536Crossref PubMed Scopus (30) Google Scholar and setting age- and sex-dependent thresholds at the fifth percentile level.8Glassock R.J. Winearls C. Routine reporting of estimated glomerular filtration rate: Not ready for prime time.Nat Clin Pract Nephrol. 2008; 4: 422-423Crossref PubMed Scopus (21) Google Scholar, 9Glassock R.J. Winearls C. An epidemic of chronic kidney disease: Fact or fiction?.Nephrol Dial Transplant. 2008; 23: 1117-1121Crossref PubMed Scopus (176) Google Scholar Obviously, the latter proposal would create a precedent for a new form of “reverse epidemiology” by defining a disease stage on the basis of a fixed prevalence rate.13Coresh J. Stevens L.A. Levey A.S. Chronic kidney disease is common: What do we do next?.Nephrol Dial Transplant. 2008; 23: 1122-1125Crossref PubMed Scopus (47) Google ScholarThese issues vary significantly in their relevance and implications, and a detailed analysis of the concerns and proposals as well as counterarguments is far beyond the scope of this commentary. However, the leadership of KDOQI, the organization that issued the CKD guideline in 2002, and of KDIGO, the foundation that endorsed the global use of the current definition and staging system of CKD, both believe that an open discussion needs to be continued in a structured way and that a rationale should be developed on how to validate the existing system as well as proposed alterations to this system.Position of KDOQI and KDIGOBoth KDOQI and KDIGO acknowledge that the ongoing debate is important and is a reflection of a self-critical appraisal of changing knowledge and practice within our discipline. The risk of overdiagnosis of CKD and inappropriate diagnosis of a kidney “disease” needs to be taken very seriously, since it may easily blunt preventive and therapeutic strategies and impair the credibility of a whole discipline. On the other hand, opportunities for improvement of patient care and appropriate recognition of patient risks should not be dismissed.The currently used definitions of CKD and of different stages of CKD are considered working definitions. Similarly, the currently available methods to estimate GFR and ascertain kidney damage are evolving. The appropriateness of these definitions, methods, and the recommendations linked to them need to be regularly reviewed as experience with their implementation is gained and in light of new knowledge, and revised as necessary. Such revisions, however, should be based on a carefully defined rationale, should follow a defined process, and should be in line with policies for disease definition and staging in other medical disciplines. The ultimate goal is that the application of a definition and staging system for kidney disease will lead to improved patient outcomes as compared to not applying it. Testing whether this goal is achieved and which CKD definition and staging system serves this purpose best is obviously not straightforward. While using common language and definitions is an indispensable initial step, the identification of therapeutic targets and strategies for intervention, followed by the vigorous validation and implementation of these strategies, are the critical steps that will eventually justify any definition and staging system. There are many examples in other areas of medicine where progress towards this goal has taken decades of stepwise iterative adaptations. It has rightly been pointed out that there is still a long way to go to make a compelling case that increased attention to measures of kidney structure and function can add substantially to the prevention of kidney failure and cardiovascular disease,5Couser W.G. Chronic kidney disease–The promise and the perils.J Am Soc Nephrol. 2007; 18: 2803-2805Crossref PubMed Scopus (48) Google Scholar but we believe that nephrology as a discipline has started along a path that is well worth continuing to travel.Disease classification systems that have been successfully employed in other fields of medicine also frequently classify different disease stages by severity. The 2 aspects generally considered to be relevant in staging the severity of a disease are symptoms and adverse consequences for patient outcomes (in other words, “prognosis”). Since CKD, unless it is far advanced, is not regularly associated with symptoms, but may have a significant impact on patient prognosis, we believe that carefully and accurately defining the prognosis of patients with CKD is an important prerequisite to move the debate on CKD definition and staging forward. Knowledge about the prognosis of patients fulfilling certain diagnostic criteria will be vital in assessing the current CKD classification system and determining what, if any, modifications to the current system are appropriate.There are many vitally important questions about the outcome of CKD that need to be considered. What is the prognosis of patients with reduced kidney function and/or markers of kidney damage in terms of survival, progressive loss of kidney function, and other relevant outcomes, including cardiovascular disease? And how does this relationship between indicators of CKD and patient prognosis differ depending on age, sex, ethnicity, and comorbid conditions? In particular, is the prognosis of elderly individuals who fulfill the current definition for CKD different from that of individuals of the same age group without reduced eGFR and/or albuminuria? Does the current system of staging CKD match with differences in patient prognosis so that a disease stage defined as more severe is associated with poorer prognosis? And if it does not, or does so only imperfectly, how could it be improved? We believe that questions such as these are of central relevance. Although data that became available during recent years have already greatly informed the debate and provided some answers, many of these questions have not yet been clarified with certainty. Of particular importance, the increasing awareness of kidney disease as a public health issue has led to the establishment of several CKD cohorts in different parts of the world that are being studied prospectively, and should provide far more solid and detailed information about CKD and patient prognosis than the many retrospective and secondary analyses that are currently available to us. In addition, large population-based cohorts should also be able to answer questions about the prognosis of individuals who fulfil the