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)