HDCN Article Review/Hyperlink

Levey AS, Bosch JP, Coggins CH, et al

Effects of diet and antihypertensive therapy on creatinine clearance and serum creatinine concentration in the MDRD study

J Am Soc Nephrol (Apr) 7:556-565 1996

This subtle but very informative study critically evaluates the use of the creatinine clearance (Ccr) and the inverse of the plasma creatinine (1/Pcr) as parameters of kidney function. In the current study these parameters were studied during modifications of dietary protein and blood pressure in patients with chronic renal failure (CRF), but the authors are clearly offering broader generalizations about the use of these parameters of kidney function.

It is widely known that Ccr is the sum of the glomerular filtration (GFR) and tubular secretion of creatinine (Tscr). In addition, the plasma level (Pcr) and total daily excretion of creatinine (Ucr x V) can vary as a consequnce of changes in dietary protein intake and, over longer periods of time, changes in muscle mass. This study attempts to further examine and quantify the relationship of these interactions.

Following a reduction in dietary protein the GFR was measured sequentially for 3 years with iothalamate. The decline in GFR was similar in the study and control groups over the period of the study. Thus a negative conclusion would be reached concerning the efficacy of a low protein diet if GFR were the sole criterion used. In contrast, the Ccr was noted to decline more rapidly in the low protein diet group compared to control and this was attributed to a greater decline in Tscr in the study group. Clearly using the Ccr as the principle criterion would lead to the conclusion that a low protein diet may be detrimental in patients with CRF. Finally, the 1/Pcr was noted to decline less rapidly in the study group because of a greater decline in the Ucr x V than the Tscr (as noted in the paper though with further explication 1/Pcr = GFR/(Ucr x V -Tscr). Focusing on the 1/Pcr would therefore lead to the apparently paradoxical conclusion that a low protein diet would be beneficial in CRF.

When the intervention in the study group was improved control of blood pressure, the GFR was again noted to decline at a rate statistically indistinguishable from control In contrast, Ccr declined less rapidly in the study group due to a slower decline in the Tscr. Finally, the decline in 1/Pcr was slower in the study group since there was no change in Ucr x V with better control of blood pressure (see formula above).

Comment: The conclusions specific to this study are that lowering dietary protein and blood pressure do not appear to prevent the ineluctable decline in renal function seen in patients with CRF. The effect of these interventions on Ccr are due to changes in Tscr while the effects on 1/Pcr are due to changes in Tscr and Ucr x V. Probably more important is the reminder that the Ccr and 1/Pcr, while simple to perform and inexpensive, do not reflect isolated changes in specific renal physiology. Studies which utilize such parameters of renal function should be interpreted with these limitations in mind. (Greg Cowell, M.D., University of Illinois at Chicago)