Widely used criteria may lead to overdiagnosis of CKD in the elderly

Two nephrologists believe CKD is being overdiagnosed in the United States, particularly among the elderly. The physicians assert that the current National Kidney Foundation (NKF) Kidney Disease Outcome Initiative (K/DOQI) criteria for staging CKD include flaws, the most serious of which is the erroneous labeling of many elderly people as having CKD stage 3.

Richard Glassock, MD, emeritus professor of medicine at the David Geffen School of Medicine at UCLA, and Christopher Winearls, FRCP, DPhil, a consultant nephrologist at the University of Oxford in England, stated that the staging system “contains the unfortunate error” of using an absolute threshold for estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 (as assessed by the Modification of Diet in Renal Disease Study formula) for defining CKD stage 3 and higher, without any corroborating evidence of kidney damage (such as concomitant overt albuminuria). In a recent issue of the Clinical Journal of the American Society of Nephrology (CJASN) (2008;3:1563-1568), the nephrologists outlined their case in a debate on the use of eGFR and the K/DOQI criteria as screening tools for CKD.

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“The consequence of this flaw is very significant in that it categorizes a substantial fraction of otherwise normal, healthy older individuals (over age 65 years) as having CKD stage 3 when they do not have any clinically relevant abnormality,” Drs. Glassock and Winearls wrote. They base this assertion on the observation that eGFR declines normally with age and reaches values less than 60 mL/min/1.73 m2 in many otherwise healthy individuals over age 60-65 years.

They suggest that this flaw can be corrected by defining the threshold for stage 3 CKD using percentiles of eGFR for age and gender derived from healthy cohorts. Including abnormal overt albuminuria as a requirement for defining stage 3 CKD would further reduce its overdiagnosis, they added.

The NKF’s K/DOQI classification system for CKD was published in 2002 and is now a widely accepted standard for diagnosing and staging CKD (Am J Kidney Dis. 2002;39[Suppl 1]:S1-S266). It defines CKD stages 1, 2, 3, and 4 as an eGFR of 90 or higher, 60-89, 30-59, and 15-29 mL/min/1.73 m2, respectively.

Stage 5 is defined as an eGFR below 15 or the need for dialysis. These eGFRs are creatinine-based estimates derived from standard formulas. Furthermore, the guidelines stipulate that they must have persisted for at least three months. Stages 1 and 2 CKD require corroborating evidence of kidney damage (e.g., abnormal albuminuria), but stages 3, 4, and 5 CKD do not have to be accompanied by any additional evidence of kidney damage.

In the previously cited issue of CJASN (pp. 1569-1572), three other nephrologists defended the K/DOQI guidelines. Michal Melamed, MD, Carolyn Bauer, MD, and Thomas Hostetter, MD, argued that there is little or no harm done if healthy older adults are misclassified as having stage 3 CKD because “even such patients should profit from avoidance of nephrotoxins and some degree of monitoring.”

In an interview with Renal & Urology News, Dr. Melamed, assistant professor of medicine and epidemiology & population health at Albert Einstein College of Medicine in Bronx, New York, said that “the present treatments for kidney disease itself are the use of medications which block the renin-angiotensin system and [produce] adequate blood pressure control. It may be argued that these measures benefit people even without CKD, such as those with cardiovascular disease or high blood pressure alone.”

In a prepared statement, the NKF defended its staging criteria, noting that “eGFR should be viewed as a necessary clinical decision tool, but a more complete clinical assessment of patients with CKD is recommended and needed.” The foundation added that it does not agree with the proposal to use age-specific percentiles to adjust the definition of CKD. “In our view, this would lead to far too many young people being considered to have CKD, and far too few older people.”

William Bennett, MD, editor-in-chief of CJASN, wrote a statement (pp.1561-1562) accompanying the commentaries by Drs. Glassock and Winearls and Drs. Melamed, Bauer, and Hostetter. He noted that it is laudable to identify undiagnosed and untreated CKD—but that the current approach has significant pitfalls.

“Does a 75-year-old woman with an eGFR of 50 mL/min/1.73 m2 really have CKD that needs evaluation or management? Even the use of the term ‘disease’ in the CKD classification connotes abnormalities that may be a burden on large numbers of people classified in this way,” Dr. Bennett stated. He added that this strategy “will also counterproductively create a population of people for whom this diagnosis is false.”

William Clark, MD, professor of medicine at the University of Western Ontario, in London, Ont., Canada, is among the experts who feel strongly that the diagnostic system is broken and must be fixed. “Four fifths of people diagnosed with CKD don’t have it, and most elderly individuals don’t have it.” The K/DOQI criteria, he stated, were “a well-intentioned effort to focus on kidney disease in the general population. But to use a cutoff of less than 60 mL/min/1.73 m2 misdiagnoses more people than it accurately diagnoses. By calling it a disease, they have medicalized something that’s normal.”

Dr. Glassock said he is convinced that “eGFR and K/DOQI have inadvertently conspired together to create a distorted and inaccurate picture of CKD—they are both in need of attention and revision before they are ready for broad use as vehicles for screening for and diagnosis of CKD.”