GFR Threshold For CKD -Challenged-
What is a normal Glomerular Filtration Rate (GFR) for a 75-year-old
woman would be misdiagnosed as CKD under current guidelines.
Controversy illustrates the problems that researchers face in arriving
at “normal” clinical values
Quote:AGREEMENT ON what are normal values in medicine often is a prerequisite to the development of clinical guidelines. But what happens if guidelines are based on arguable definitions of normal? The result could be the misdiagnosis of patients, as contended recently by Richard J. Glassock, MD, emeritus professor at the David Geffen School of Medicine, University of California, Los Angeles, and U.K. nephrologist Christopher Winearls, MD. Drs. Glassock and Winearls challenged guidelines for diagnosing CKD and assert that many individuals are being wrongly diagnosed as having renal disease.
First, some background. Last October, the U.S. Renal Data System (USRDS) announced that a 30% increase in CKD over the past decade had prompted this division of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to issue its first-ever separate report documenting the magnitude of this condition. According to the USRDS, CKD affects an estimated 27 million Americans. The accuracy of this estimate, however, depends on what glomerular filtration rate (GFR) is considered normal.
Dr. Glassock observed that the CKD definition used by the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines “encompasses a significant number of normal people and erroneously—at least in my opinion—defines them as having disease. When patients are diagnosed with CKD but don't have it, the potential harm ranges from causing them anxiety and worry to undergoing expensive testing to possibly even losing their health insurance.”
The controversy stems from the fact that serum creatinine measurements are done in nearly all inpatients and a high percentage of outpatients, even those simply making routine visits for preventive primary care. “Whenever a serum creatinine test is done, an estimated glomerular filtration rate, or eGFR, is also calculated according to the standard MDRD [Modification of Diet in Renal Disease study]equation,” Dr. Glassock explains.
“The KDOQI group did not adjust the thresholds differentiating normal from abnormal based on age and gender, and that, in my view, was a serious mistake because eGFR declines in all people as they age everyone,” Dr. Glassock asserts. “If the KDOQI guidelines applied only to white males under the age of 45, the KDOQI criteria are just fine, but 80% of people diagnosed as having CKD using these criteria are over 65. The normal GFR in a 75-year-old woman is close to 40 [mL/min] rather than 60, but KDOQI calls less than 60 chronic kidney disease, so the problem is that elderly women in particular are being overdiagnosed as having CKD by the KDOQI criteria. For a 75-year-old man, normal is about 45 or 50.”
Dr. Glassock says the data so far seem to indicate that the number of patients who were “appropriately referred that is, who have true kidney disease is far, far less than [the number] who were referred inappropriately and who do not have kidney disease.”
He calls the 2002 adoption of the guidelines premature. “The KDOQI working group should have waited until better data were available to identify what the proper criteria were, or [they should have] come back and revised them after they found the criteria were incorrect,” Dr. Glassock says. “That hasn't happened.”
Drs. Glassock and Winearls took their concerns to the “Controversies in Nephrology” section of the Clinical Journal of the American Society of Nephrology (2008;3:1563-1568). They objected to the screening of unselected populations not known to be at risk of CKD by means of the eGFR formula, KDOQI staging system, and other tools “of dubious value,” warning of the inherent dangers of such screening. This was published alongside counterarguments presented by the Thomas Hostetter, MD, director of the Nephrology Division at Albert Einstein College of Medicine, Bronx, N.Y., and fellow Einstein nephrologists Michal L. Melamed, MD, and Carolyn Bauer, MD. The group noted that mass or universal screening was not the purpose of eGFR reporting, agreed it did not seem justified, and even agreed that the KDOQI staging system leads to “disturbingly high estimates” of CKD.
But Dr. Hostetter and his co-authors advocated eGFR as just one tool that can be used to help reduce the “even more disturbing fraction of people with serious and progressive renal disease who are not diagnosed, counseled, or treated.”
“I think laboratories ought to report if creatinine leads to an estimated GFR less than 60; I think that's perfectly justifiable,” remarks Dr. Hostetter, a one-time director of the NIH's National Kidney Disease Education Program (NKDEP). “All it does is provide a more meaningful reflection of kidney function for clinicians who are not kidney doctors. I'm not a big proponent of staging, of saying you have stage 3 or stage 4 or stage 5. The laboratories just ought to report the estimated GFR, whatever it is.”
Specifically, the eGFR is beneficial in identifying patients who should avoid certain drugs that can further harm the kidneys, who should be taking ACE inhibitors or angiotensin receptor blockers to slow the progression of kidney disease, and, in extreme cases, who need dialysis or kidney transplantation. “I just think that without knowing what the GFR is, those things are hit or miss,” Dr. Hostetter says. “However, the eGFR is kind of rough at its very, very best, and some nephrologists have mistaken ideas about how accurately it can ever be measured. That creates problems.”
All in all, Dr. Hostetter is comfortable with the science that was used to establish the eGFR thresholds for CKD. “With any kind of laboratory test, even a blood pressure measurement, there has to be some kind of judgment in what to do. None of these is going to be driven algorithmically by a robot. With eGFR, we know that there's some error in it, but there's some error in every measurement we make.”
Like Dr. Hostetter, current NKDEP director Andrew S. Narva, MD, believes that the answer is not to abandon use of the eGFR measurement but to make sure that clinicians understand its limitations. “The eGFR using the MDRD equation is the best estimating tool we have, but it's simply an estimate,” he says.
Actual GFR had been employed mostly as a research tool, but it is being used more and more in certain clinical settings. The validity of any GFR measurement is compromised by the fact that as a product of muscle breakdown, creatinine is affected by age, gender, race, and even diet. “Creatinine is only useful when it's stable, and there have been many misuses of eGFR and other creatinine-based estimates of kidney function because they were applied at a time when the creatinine was actually changing,” Dr. Narva says. “That gives a very misleading impression of what kidney function is.”
He likens the relationship between estimated and actual GFR to the estimated date of confinement for a pregnant woman compared with her actual due date. “It's the best predictor of when a woman will deliver, but in fact women will deliver in a bell-shaped curve around that due date; most won't actually deliver on that due date.”
The NKF calls eGFR a useful first step in CKD detection, evaluation, and management but not the last step. “GFR is not the only determinant of risk,” the foundation commented in a statement to Renal & Urology News. “Thus, eGFR should be viewed as a necessary clinical decision tool, but a more complete clinical assessment of patients with CKD is recommended and needed. Studies that use the combination of proteinuria and eGFR to estimate risk are being published and are a first step toward this goal.”
The NKF does not agree with the proposal to use age-specific percentiles to adjust the definition of CKD. “If the fifth percentile of creatinine or eGFR for each age, sex, and race group is defined as abnormal, then the prevalence of CKD would be 5% for all groups. In our view, this would lead to far too many young people and far too few older people being considered to have CKD.”
Instead, percentiles “could be based on a healthy elderly group, resulting in a less steep age-related increase in CKD than observed using the current cutoff level for eGFR.” Defining “healthy” in older individuals is problematic, however. “The main rationale appears to be avoiding classification of a large number of elderly people as having CKD with limited treatment options. However, it is not appropriate to define a disease based on the number of people classified as diseased or whether treatment is available.”
The NKF notes that it is “striking” that 38% of individuals older than 70 are classified as having CKD on the basis of decreased eGFR. The organization puts that figure in perspective, however, by noting that diabetes prevalence among people over age 65 is 22% and hypertension and hypercholesterolemia are far more common. “Inadequate treatment for common diseases should be a challenge for future research rather than a reason for changing the definition of what is normal.”
~The most important things in the world
were accomplished by people who have
kept on trying when there seemed to be
no hope left~