Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.
BACKGROUND
The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown. We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study.


METHODS
Study A was a randomized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate (25 to 55 mL/min/1.73 m(2) [0.42 to 0.92 mL/s/1.73 m(2)]) assigned to a low- versus usual-protein diet (0.58 versus 1.3 g/kg/d). We used registries to ascertain the development of kidney failure (initiation of dialysis therapy or transplantation) or a composite of kidney failure and all-cause mortality through December 31, 2000. We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet, adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate. We estimated hazard ratios for the entire follow-up period and then, in time-dependent analyses, separately for 2 consecutive 6-year periods of follow-up.


RESULTS
Kidney failure and the composite outcome occurred in 327 (56%) and 380 patients (65%), respectively. After adjustment for baseline factors, hazard ratios were 0.89 (95% confidence interval [CI], 0.71 to 1.12) and 0.88 (95% CI, 0.71 to 1.08), respectively. Adjusted hazard ratios for both outcomes were lower during the first 6 years (0.68; 95% CI, 0.51 to 0.93 and 0.66; 95% CI, 0.50 to 0.87, respectively) than afterward (1.27; 95% CI, 0.90 to 1.80 and 1.29; 95% CI, 0.94 to 1.78; interaction P = 0.008 and 0.002, respectively). Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial.


CONCLUSIONS
The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive. Future studies should include a longer duration of intervention and follow-up.
Levey
Andrew S
AS
Division of Nephrology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Greene
Tom
T
Sarnak
Mark J
MJ
Wang
Xuelei
X
Beck
Gerald J
GJ
Kusek
John W
JW
Collins
Allan J
AJ
Kopple
Joel D
JD
D001794:Blood Pressure; D018753:Diet, Protein-Restricted; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000178:diet therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007690:Polycystic Kidney Diseases / Q000178:diet therapy; D012044:Regression Analysis