Time for a change?

This month's issue of NDT has an interesting debate concerning whether or not clinical laboratories should start reporting CKD-EPI GFR instead of MDRD. The pro side is here while the con side is here. Basically, the argument for changing is that there is less bias in the CKD-EPI equation, it is more accurate at higher GFRs and more accurately classifies patients as stage 3 as opposed to stage 2 (in terms of overall prognosis). The counter-argument is that, although there is a slight decrease in bias associated with the use of CKD-EPI, it is not any more precise than MDRD - this is more a fault of creatinine as a test of renal function rather than a specific problem with the equations. It should also be mentioned that the CKD-EPI equation is not necessarily better in all circumstances - as documented by Leo in this post about renal transplant recipients.

To (perhaps) settle the argument on one side, the moderator of the debate wrote a commentary and came down on the side of changing to the CKD-EPI equation. The argument is that, even if the improvement is slight, we, as a nephrology community, should not settle for something that is clearly inferior in most circumstances. MDRD was developed in a population of patients with CKD and therefore does not accurately reflect GFR in healthy populations. For this reason, in the research community, there has been a move towards more use of CKD-EPI in the recent past as it is more appropriate for epidemiologic research. The switch to CKD-EPI would not require the use of any new analytes - a simple change in coding in the computers reporting results. In fact, a number of organizations have already switched.

Two other things to mention. Neither equation has been properly validated in Asian populations and this needs to be remedied. Secondly, the role for cystatin C-based or combination equations is still uncertain. Cystatin C is a better predictor of outcomes than creatinine but there are many non-GFR determinants of cystatin C that are likely biasing this and are not related to renal function. Also, the cystatin C test is expensive and has not been fully standardized. There may be a place for the combination equation in patients with borderline GFRs (45-60) in whom the diagnosis of CKD is uncertain.

MDRD vs CKD-EPI in Transplantation

With the results of the eAJKD brackets posted by Gearoid, I thought this article might be pertinent to stimulate further the debate... This article just came out on Transplantation and is a well designed study in which the performance of the CKD-EPI equation is compared with the MDRD Study equation in 825 stable kidney transplant recipients.
GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337).
The results showed that bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine to estimate the GFR. This superiority translated into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation was confirmed both in the subgroups of patients with mGFR below 60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR above 90 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance.
The data also bring us back to the main concern about using creatinine and how poor of a marker it is for renal function. About 30% are misclassified in the CKD stages...  The battle is far from over...

A picture is worth...

Often on rounds with medical students or housestaff we will review why a serum creatinine of 0.8 mg/dl in a 40 year old athlete...


may mean a much higher creatinine clearance than a creatinine of 0.8 mg/dl in a sedentary 74 year old grandfather...


due to the much lower muscle mass and subsequent lower creatinine production in the older individual.

The beautiful cross sectional MRI images above are a stunning visual reminder of muscle mass differences that we only guess at from external appearances.

The good news is that aging alone does not relegate one to inevitable muscle mass decline and frailty. The images are taken from an interesting study in The Physician and Sportmedicine examining muscle mass and function in men and women in each of four age categories: 40s, 50s, 60s and older than 70. The subjects were all considered masters level athletes engaging in training exercise 4-5 times per week.

In these individuals muscle mass and function did not decline with age though they did gain body fat. Compare the muscle area and appearance of the 74 year old sedentary male above to the 70 year old male athlete below...


The lesson: Stay active, keep your kidneys healthy and keep that creatinine of 0.8 mg/dl reflecting the same creatinine clearance at 70 years old as it did at 40!