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

Andrew S. Levey, Tom Greene, Mark J. Sarnak, Xuelei Wang, Gerald J. Beck, John W. Kusek, Allan J. Collins, Joel D. Kopple

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139 Scopus citations


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 m2 [0.42 to 0.92 mL/s/1.73 m2]) 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)879-888
Number of pages10
JournalAmerican Journal of Kidney Diseases
Issue number6
StatePublished - Dec 2006
Externally publishedYes


  • Chronic kidney disease (CKD)
  • clinical trial
  • low-protein diet


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