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Effects of dietary protein restriction on the progression of advanced renal disease in the modification of diet in renal disease study
Abstract
Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.
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“In the MDRD study (Modification of Diet in Renal Disease), a dietary protein target of 0.6 g·kg−1·d−1 appeared to limit progression of CKD, at least during the 6-year follow-up time frame.125,126”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [126]
Citations
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The modification of diet in renal disease study group
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Self-citationA method for estimating nitrogen intake of patients with chronic renal failure
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Research works printed but not linked: 2
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Levey, A. S., Bosch, J. P., Lewis, J. B., Greene, T., Rogers, N., Roth, D., & for the Modification of Diet in Renal Disease Study Group* (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-6-199903160-00002 · Cited by 15,079
Self-citationKDOQI clinical practice guideline for nutrition in CKD: 2020 update
Ikizler, T. A., Burrowes, J. D., Byham-Gray, L. D., Campbell, K. L., Carrero, J.-J., Chan, W., Fouque, D., Friedman, A. N., Ghaddar, S., Goldstein-Fuchs, D. J., et al. (2020) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2020.05.006 · Cited by 1,960
Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients
American Society for Parenteral and Enteral Nutrition (2002) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607102026001011 · Cited by 758
Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study
Modification of Diet in Renal Disease Study Group, Hunsicker, L. G., Adler, S. G., Caggiula, A. W., England, B. K., Greene, T., Kusek, J. W., Rogers, N. L., Teschan, P. E., & Beck, G. J. (1997) · Kidney International · doi:10.1038/ki.1997.260 · Cited by 698
Self-citationEffect of lipid reduction on the progression of renal disease: A meta-analysis
Fried, L. F., Orchard, T. J., & Kasiske, B. L. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.00487.x · Cited by 662
Metadata
- Authors
- Levey, A. S., Adler, S., Caggiula, A. W., England, B. K., Greene, T., Hunsicker, L. G., Kusek, J. W., Rogers, N. L., & Teschan, P. E.
- Affiliations
- National Institutes of Health (US)
- Venue
- American Journal of Kidney Diseases
- Publisher
- Elsevier BV
- Published
- 1996-05
- Volume
- 27
- Issue
- 5
- Pages
- 652-663
- ISSN
- 0272-6386 (ISSN-L)
- OpenAlex
- W1995286167
- Cited by
- 334
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 11 · 2013: 18 · 2012: 14
- FWCI
- 16.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Kidney Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Keywords
- protein restriction, very low protein diet, chronic kidney disease progression, glomerular filtration rate decline, MDRD Study, protein intake, renal failure, proteinuria, proteinuria reduction
- MeSH terms
- Adolescent, Adult, Aged, Amino Acids, Chronic Disease, Creatinine, Dietary Proteins, Female, Follow-Up Studies, Food, Fortified, Glomerular Filtration Rate, Humans, Keto Acids, Kidney Diseases, Male, Middle Aged, Proteinuria, Treatment Outcome, Disease Progression, Diet, Protein-Restricted, Renal Insufficiency
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