EFFECTS OF DIETARY-PROTEIN RESTRICTION ON THE PROGRESSION OF MODERATERENAL-DISEASE IN THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY

The Modification of Diet in Renal Disease (MDRD) Study consisted of tw o randomized controlled trials to determine the effects of dietary pro tein restriction and strict blood pressure control. In 255 patients wi th advanced renal disease (baseline GFR, 13 to 24 mL/min per 1.73 m(2) ; Study B), secondary analyses demonstrated a correlation between achi eved protein intake and rate of decline in GFR, consistent with a bene ficial effect of a low-protein diet. In 585 patients with moderate ren al disease (baseline GFR, 25 to 55 mL/min per 1.73 m(2); Study A), the primary analysis of the effect of the low-protein diet was inconclusi ve because of a nonlinear GFR decline and limited duration of follow-u p. A meta-analysis of recent controlled trials, including MDRD Study A , demonstrated a beneficial effect of a low-protein diet on the incide nce of renal failure. The objective of these secondary analyses is to explore further the effect of dietary protein restriction in Study A. In these analyses, a total of 585 patients were randomly assigned to f ollow either a low-protein diet (0.58 g/kg per day) or a usual-protein diet (1.3 g/kg day). Outcomes included the rate of GFR decline, incid ence of renal failure or death, and change in urine protein excretion. Analyses included comparisons of randomized groups and correlations o f outcomes with achieved protein intake. The comparisons of randomized groups revealed a faster GFR decline during the first 4 months after assignment to the low-protein diet but no difference in the variabilit y in GFR decline between the diet groups, indicating a uniform short-t erm effect of the low-protein diet on GFR, probably as a result of hem odynamic adjustments. After 4 months, the mean decline in GFR in the l ow-protein diet group was slower, and the variability of the rate of d ecline was smaller, than in the usual-protein diet group (ratio of sta ndard deviations, 0.73; 95% confidence interval, 0.55 to 0.91; P < 0.0 1). This suggests a greater beneficial effect of the low-protein diet in patients with a more rapid GFR decline. The net effect of the low-p rotein diet on GFR decline over 3 yr was no significant change in mean GFR decline, but reduced variability of the decline (ratio of standar d deviations, 0.76; 95% confidence interval, 0.60 to 0.92; P < 0.01). Correlational analyses revealed trends similar to the comparisons of r andomized groups. During the first 4 months, patients with a greater d ecline in protein intake (irrespective of diet group) had a greater de cline in GFR; thereafter, patients with a lower protein intake had a s lower GFR decline. Over 3 yr, there was no significant correlation bet ween GFR decline and achieved protein intake. The correlation of prote in intake with GFR decline after 4 months was less strong than observe d in Study B. The relative risk of death or renal failure was 0.65 (95 % confidence interval, 0.38 to 1.10; P = 0.10) in patients assigned to the low-protein diet group compared with the usual-protein diet group , which is similar to that observed in the meta-analysis. During follo w-up, the increase in urine protein excretion was delayed in the low-p rotein diet group (P = 0.008) and in patients with lower achieved prot ein intake (P = 0.005). In summary, the absence of a significant diffe rence between the diet groups in the mean change in GFR from baseline to 3 yr precludes a definitive conclusion of a beneficial effect of th e diet intervention based solely on MDRD Study A. However, these secon dary analyses are consistent with a beneficial effect of the low-prote in diet to slow the GFR decline in patients with the most rapidly decl ining GFR and to reduce urine protein excretion. These results, togeth er with the results of the recent meta-analysis (including MDRD Study A), provide some support for the hypothesis that dietary protein restr iction slows the progression of moderate renal disease.