Specifically,the eGFR is beneficial in identifying patients who should avoid certain drugsthat can further harm the kidneys, who should be taking ACE inhibitors orangiotensin receptor blockers to slow the progression of kidney disease, and,in extreme cases, who need dialysis or kidney transplantation. “I just thinkthat without knowing what the GFR is, those things are hit or miss,” Dr.Hostetter says.


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“However, the eGFR is kind of rough at its very, very best, andsome nephrologists have mistaken ideas about how accurately it can ever bemeasured. That creates problems.”

Allin all, Dr. Hostetter is comfortable with the science that was used toestablish the eGFR thresholds for CKD. Withany kind of laboratory test, even a blood pressure measurement, there has to besome kind of judgment in what to do. None of these is going to be drivenalgorithmically by a robot. With eGFR, we know that there’s some error in it,but there’s some error in every measurement we make.”

LikeDr. Hostetter, current NKDEP director Andrew S. Narva, MD, believes that theanswer is not to abandon use of the eGFR measurement but to make sure thatclinicians understand its limitations. “The eGFR using the MDRD equation is thebest estimating tool we have, but it’s simply an estimate,” he says.

ActualGFR had been employed mostly as a research tool, but it is being used more andmore in certain clinical settings. The validity of any GFR measurement iscompromised by the fact that as a product of muscle breakdown, creatinine isaffected by age, gender, race, and even diet.

“Creatinine is only useful whenit’s stable, and there have been many misuses of eGFR and othercreatinine-based estimates of kidney function because they were applied at atime when the creatinine was actually changing,” Dr. Narva says. “That gives avery misleading impression of what kidney function is.”

He likensthe relationship between estimated and actual GFR to the estimated date ofconfinement for a pregnant woman compared with her actual due date. “It’s thebest predictor of when a woman will deliver, but in fact women will deliver ina bell-shaped curve around that due date; most won’t actually deliver on thatdue date.”

The NKF calls eGFR a useful first step in CKD detection,evaluation, and management but not the last step. “GFR is not the onlydeterminant of risk,” the foundation commented in a statement to Renal & Urology News. “Thus, eGFRshould be viewed as a necessary clinical decision tool, but a more completeclinical assessment of patients with CKD is recommended and needed. Studiesthat use the combination of proteinuria and eGFR to estimate risk are beingpublished and are a first step toward this goal.”

(Portions of the full NKF statement,which has been edited here for space, originally appeared in a report by JosefCoresh, MD, PhD; Lesley Ann Stevens, MD; and Andrew S. Levey, MD [Nephrol Dial Transplant. 2008;23:1122-1125]. Additional comments were added by Kerry Willis, PhD,NKF senior vice president for scientific activities.)

The NKF does not agree with the proposal to use age-specificpercentiles to adjust the definition of CKD. “If the fifth percentile ofcreatinine 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 wouldlead to far too many young people and far too few older people being consideredto have CKD.”


Instead, percentiles “could be based on a healthy elderlygroup, resulting in a less steep age-related increase in CKD than observedusing the current cutoff level for eGFR.” Defining “healthy” in olderindividuals is problematic, however. “The main rationale appears to be avoidingclassification of a large number of elderly people as having CKD with limitedtreatment options. However, it is not appropriate to define a disease based onthe number of people classified as diseased or whether treatment is available.”


The NKF notes that it is “striking” that 38% of individualsolder than 70 are classified as having CKD on the basis of decreased eGFR. Theorganization puts that figure in perspective, however, by noting that diabetesprevalence among people over age 65 is 22% and hypertension andhypercholesterolemia are far more common. “Inadequate treatment for commondiseases should be a challenge for future research rather than a reason forchanging the definition of what is normal.”


Another gray area in the management of kidney disease is thelevel to which anemia should be corrected. “Almost all people with kidneyfailure get erythropoietin to keep their hemoglobin up, but we’ve learned thatit shouldn’t be kept at the level [considered] normal for people without CKD,” Dr.Hostetter says. “It’s still a little uncertain about what the optimal level is,though.”

For people not in kidney failure, the normal range forhemoglobin is 13-15 g/dL of blood. For kidney failure patients, who often feelweak and need transfusions when their hemoglobin falls to 5 or 6 g/dL, 10-11g/dL is about the right range.

“About 10 years ago, trials started to show us that,surprisingly, bringing dialysis patients any higher would actually make them doworse in terms of feeling weak and needing transfusions,” Dr. Hostetterobserves. “Now trials are looking for the sweet spot in between, to refine whatthe normal level is.”

The NKF has been a leader in formulating opinion-basedguidelines to bridge the gap when randomized controlled trials couldn’t clarifythat normal threshold, but the organization courted controversy a few years agowhen its work got support from Amgen, a manufacturer of drugs that counteranemia. “I think in the long run, the NKF has done the right thing and hastried to come up with the best guess. There are some ongoing trials trying todefine more scientifically exactly at what level the hemoglobin should be,” Dr.Hostetter concludes.


“It’s a little different from eGFR, but once again, youtry to find the number that suits the epidemiology and the clinical trial data,[then set the point at which] a disease or a condition needs to be treated.Hemoglobin is a little funny because, for reasons I don’t think anybodyunderstands, raising the hemoglobin of people with kidney failure to a normallevel leads to worse outcomes.”