Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study

Am J Kidney Dis. 2009 Feb;53(2):208-17. doi: 10.1053/j.ajkd.2008.08.009. Epub 2008 Oct 31.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acids / administration & dosage
  • Chronic Disease
  • Diet, Protein-Restricted*
  • Dietary Supplements
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Keto Acids / administration & dosage
  • Kidney Diseases / diet therapy*
  • Male
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency / mortality
  • Renal Insufficiency / prevention & control
  • Survival Analysis


  • Amino Acids
  • Keto Acids