Effect of a Very Low-Protein Diet on Outcomes: Long-term Follow-up of the Modification of Diet in Renal Disease (MDRD) Study

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

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202 Scopus citations


Background: The long-term effect of a very low-protein diet on the progression of kidney disease is unknown. We examined the effect of a very low-protein diet on the development of kidney failure and death during long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Study Design: Long-term follow-up of study B of the MDRD Study (1989-1993). Setting & Participants: The MDRD Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 255 trial participants with predominantly stage 4 nondiabetic chronic kidney disease. Intervention: A low-protein diet (0.58 g/kg/d) versus a very low-protein diet (0.28 g/kg/d) supplemented with a mixture of essential keto acids and amino acids (0.28 g/kg/d). Outcomes: Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality until December 31, 2000. Results: Kidney failure developed in 227 (89%) participants, 79 (30.9%) died, and 244 (95.7%) reached the composite outcome of either kidney failure or death. Median duration of follow-up until kidney failure, death, or administrative censoring was 3.2 years, and median time to death was 10.6 years. In the low-protein group, 117 (90.7%) participants developed kidney failure, 30 (23.3%) died, and 124 (96.1%) reached the composite outcome. In the very low-protein group, 110 (87.3%) participants developed kidney failure, 49 (38.9%) died, and 120 (95.2%) reached the composite outcome. After adjustment for a priori-specified covariates, hazard ratios were 0.83 (95% confidence interval, 0.62 to 1.12) for kidney failure, 1.92 (95% confidence interval, 1.15 to 3.20) for death, and 0.89 (95% confidence interval, 0.67 to 1.18) for the composite outcome in the very low-protein diet group compared with the low-protein diet group. Limitations: Lack of dietary protein measurements during follow-up. Conclusion: In long-term follow-up of the MDRD Study, assignment to a very low-protein diet did not delay progression to kidney failure, but appeared to increase the risk of death.

Original languageEnglish (US)
Pages (from-to)208-217
Number of pages10
JournalAmerican Journal of Kidney Diseases
Issue number2
StatePublished - Feb 2009

Bibliographical note

Funding Information:
Support: This study was supported by grants K23 DK067303, K23 DK02904, K24 DK078204, and UO1 DK35073 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD). The NIDDKD had no role in the design, conduct, and analysis of this study or in the decision to submit the manuscript for publication. Drs Sarnak, Menon, Greene, and Wang had full access to the data.


  • Chronic kidney disease
  • low-protein diet
  • outcomes


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