KDIGO Controversies Conference: Reaches Consensus on Definition, Classification, and Prognosis of Chronic Kidney Disease

Over the past few years, controversy over the definition and classification of chronic kidney disease (CKD) has played out in the editorial pages of nephrology journals. Although the debate occurred primarily among nephrologists, the controversy has implications for the care of CKD across all disciplines of medicine. A recently reached consensus on revisions to the classification of CKD based on prognosis may help to quell the controversy. The revisions do not change the definition of CKD.

The revisions arose from a Controversies Conference on “Chronic Kidney Disease: Definition, Classification and Prognosis” sponsored by Kidney Disease Improving Global Outcomes (KDIGO). KDIGO is an international nonprofit organization whose purpose is to improve the care and outcomes of kidney disease patients worldwide by promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines.

Before the conference, held in October, widespread agreement existed that kidney failure (stage 5 CKD) is a life-threatening condition, with increasing prevalence around the world, high cost, and poor outcomes. In the United States, the prevalence of kidney failure treated by dialysis and transplantation is approximately 0.2 percent of the population (500,000 people), with an annual cost of $35 billion. Kidney disease is silent in its early stages, but can be detected by commonly available laboratory tests, such as serum creatinine to estimate glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (ACR) as a marker of kidney damage. Earlier detection and treatment could potentially reduce disease complications and the risk of developing kidney failure.

The controversies aired at the conference centered on the current definition and classification of kidney disease, proposed by the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) in 2002 and subsequently adopted, with minor modifications, by KDIGO in 2005. The guidelines define CKD as either GFR <60 mL/min/1.73 m2 (less than half of the normal level in young adults) or kidney damage for >3 months, regardless of cause of disease. A urine albumin-to-creatinine ratio >30 mg/g is defined as a marker of kidney damage.

In people with CKD, the disease is further classified by the level of GFR (known as stages). Population surveys of estimated GFR and urinary ACR identify between 11 and 12 percent of the U.S. adult population as having CKD using this definition (23 million people). The prevalence of CKD is as high as 40 percent among people over 70, primarily because of the large number of people with GFR 30–59 mL/min/1.73 m2 (CKD stage 3), many of whom do not have elevated ACR. The prognosis of earlier stages of CKD is highly variable, with more people dying of cardiovascular disease (CVD) than kidney failure.

Based on similar findings around the world, the International Society of Nephrology and International Federation of Kidney Foundations adopted the message for World Kidney Day in 2008 that “CKD is common, harmful, and treatable.” One of the purposes of the KDIGO conference was to identify absolute and relative risks of complications of CKD, including all-cause mortality, CVD mortality, kidney failure, acute kidney injury, and progressive kidney disease.

Overdiagnosis of CKD a concern

The main concern about the current definition and classification was the possibility of overdiagnosis of CKD and overuse of resources in the investigation and management of CKD, without appropriate modifications for variations in prognosis. Specific issues raised were the appropriateness of the GFR thresholds, albuminuria thresholds, and absence of age modifications—since lower GFR levels and higher albumin excretion rates are commonly observed in the apparently “healthy” elderly.

Underlying these controversies was concern regarding the methods for assessing eGFR and albuminuria, and discomfort with the term “disease” for labeling a large number of people, mostly elderly, with lower levels of GFR and albuminuria.

In response to this debate, the KDIGO Board of Directors convened the Controversies Conference to review and possibly suggest revisions to the definition and classification of CKD, in light of current knowledge regarding its prognosis, with the goal of improving patient outcomes. KDIGO appointed a Planning Committee chaired by Andrew Levey, MD (U.S.), and co-chaired by Meguid El Nahas, MD (U.K.), Paul de Jong, MD (NL), and Josef Coresh, MD, PhD (U.S.). The KDIGO Controversies Conference was tasked with addressing five questions:

  1. What are the key outcomes of CKD?
  2. What progress has been made in CKD testing (eGFR and albuminuria)?
  3. What are the key factors determining prognosis of CKD (e.g., eGFR, albuminuria)?
  4. Should the current CKD classification (based on eGFR) be modified to include additional factors associated with prognosis?
  5. Should the current CKD definition be modified?

The planning committee invited representatives of studies to contribute data on outcomes of CKD in clinical or research populations in which eGFR and albuminuria had been determined at baseline. Outcomes considered included all-cause mortality, CVD mortality, kidney failure treated by dialysis or transplantation (end stage renal disease), acute kidney injury, and decline in eGFR (progressive CKD). An analytical committee provided a uniform analysis plan for systematic evaluation of the data for each cohort and performed meta-analyses of results provided by the studies.

Altogether, more than 50 cohorts submitted data and participated in the conference. Meta-analyses on 1.5 million study participants on a range of outcomes were performed and reviewed. A databook consisting of 1704 pages of cohort data and 464 pages of results of meta-analyses was distributed to all conference participants.

The conference consisted of plenary sessions during which KDIGO Co-Chairs Bertram Kasiske, MD (U.S.), and Kai-Uwe Eckardt, MD (Germany), members of the Planning Committee, Richard Glassock, MD (U.S.), a noted critic of the current definition and classification, and other experts on CKD outlined the background and objectives of the conference. Following plenary sessions, conference participants broke out into smaller groups for in-depth discussions of data and a proposal for revisions, and then reconvened in a plenary session for expression of viewpoints on a number of subjects, including a nonbinding vote on questions prepared by the organizers.

The data reviewed showed a strong, consistent gradation in risk for all outcomes of CKD according to the level of estimated GFR and urine ACR across a wide range of study populations. Interestingly, the gradation was linear for all levels of albumin excretion and nonlinear for GFR. In general, increased risk for CKD was noted below a level of GFR around 60 mL/min/1.73 m2 and at urinary ACR at all levels above 10 mg/g (the lowest value examined). The risk for cardiovascular mortality and kidney disease outcomes tended to be elevated at a higher eGFR than all-cause mortality. In addition, risk varied according to the cause of kidney disease and other factors, such as age, CVD risk factors, diabetes, hypertension, smoking, hypercholesterolemia, and history of CVD.

A strong consensus reached by those present was that the current classification did not adequately describe the severity of CKD, and that predicting prognosis could be improved by the following modifications to the classification:

  1. Emphasize classification by cause, if known, in addition to stage.
  2. Add albuminuria stages, in addition to GFR stages (ACR < 30 mg/g, 30–300 mg/g, and >300 mg/g).
  3. Subdivide CKD stage 3 into two stages (GFR 30–44 and 45–59 mL/min/1.73 m2).

Consensus also emerged that it would be premature to change the current definition of CKD based on levels of GFR or presence of kidney damage. The following recommendations were also adopted by those present:

  1. Make no change to the definition based on GFR (<60 mL/min/1.73 m2), regardless of age or sex.
  2. Make no change to the level of albuminuria defined as a marker of kidney damage (urine ACR >30 mg/g).

These recommendations need to be codified by a guidelines development group that would include a broader array of disciplines.

The immense and unique database provided by the meta-analyses described at the Controversies Conference will supply a valuable resource upon which to base new guidelines for the diagnosis, classification, and prognosis of CKD.

For the time being, CKD prevalence estimates will remain unchanged, and will continue to include a large fraction of the elderly population. However, a modified classification that includes cause of disease (if known) and albuminuria stages, in addition to GFR stages, will relate better to prognosis than the staging based solely on GFR. This may be particularly helpful in the great majority of elderly individuals with reduced GFR—albuminuria staging may better define their risk for mortality and kidney disease outcomes. Improved information on prognosis can be helpful for a large number of management decisions, including decisions on who to refer to nephrologists.

As a consequence of this landmark meeting—designed to assess the controversies but not to develop new guidelines—it is anticipated that revision of the 2002 KDOQI clinical practice guidelines on definition and classification of CKD will be undertaken by KDIGO in the near future.

After the meeting, Glassock commented: “The Controversies Conference was truly a historical event that will propel this entire field to a new level. The openness of the debate, the rigor of the questions and answers, and the immensity of the data and its analysis was truly remarkable. While much work remains to be done on refining the classification, diagnosis, and prognosis of CKD, there is no doubt that the end product will have as its origins the findings and discussions that were in evidence at the London meeting.”

In summarizing the outcome of the conference, Levey said, “The debate reflects a tension in our field caused by the paradigm shift about the basic perspective on CKD—from kidney failure as a life-threatening illness to earlier stages of kidney disease as the target for prevention, detection, evaluation, and management. While change is always difficult, especially for those in its midst, the debate has been healthy, and the discussions and consensus should enable us to move on and work across disciplines to improve outcomes for our patients.”

A report from the conference was presented at the American Society of Nephrology annual meeting in San Diego and will be published in Kidney International.