American Journal of Kidney Diseases
Volume 53, Issue 2 , Pages 208-217 , February 2009

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, MD, PhD

      Affiliations

    • Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA
    • ,
  • Joel D. Kopple, MD

      Affiliations

    • Division of Nephrology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, UCLA School of Public Health, Los Angeles, CA
    • ,
  • Xuelei Wang, MS

      Affiliations

    • Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, OH
    • ,
  • Gerald J. Beck, PhD

      Affiliations

    • Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, OH
    • ,
  • Allan J. Collins, MD

      Affiliations

    • Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN
    • ,
  • John W. Kusek, PhD

      Affiliations

    • National Institutes of Health, Bethesda, MD
    • ,
  • Tom Greene, PhD

      Affiliations

    • Division of Clinical Epidemiology, University of Utah, Salt Lake City, UT
    • ,
  • Andrew S. Levey, MD

      Affiliations

    • Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA
    • ,
  • Mark J. Sarnak, MD, MS

      Affiliations

    • Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA
    • Corresponding Author InformationAddress correspondence to Mark J. Sarnak, MD, MS, 800 Washington St, #391, Boston, MA 02111

Received 28 February 2008 ,Accepted 7 August 2008.

References 

  1. Hostetter TH, Meyer TW, Rennke HG, Brenner BM. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int. 1986;30:509–517
  2. Salusky I, Kleinknecht C, Broyer M, Gubler MC. Prolonged renal survival and stunting, with protein-deficient diets in experimental uremia (Reversal of these effects by addition of essential amino acids). J Lab Clin Med. 1981;97:21–30
  3. Ihle BU, Becker GJ, Whitworth JA, Charlwood RA, Kincaid-Smith PS. The effect of protein restriction on the progression of renal insufficiency. N Engl J Med. 1989;321:1773–1777
  4. Mitch WE, Walser M, Steinman TI, et al. The effect of a keto acid-amino acid supplement to a restricted diet on the progression of chronic renal failure. N Engl J Med. 1984;311:623–629
  5. Rosman JB, ter Wee PM, Meijer S, et al. Prospective randomised trial of early dietary protein restriction in chronic renal failure. Lancet. 1984;2:1291–1296
  6. Walser M, Hill SB, Ward L, Magder L. A crossover comparison of progression of chronic renal failure: Ketoacids versus amino acids. Kidney Int. 1993;43:933–939
  7. Locatelli F, Alberti D, Graziani G, et al. Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency (Northern Italian Cooperative Study Group). Lancet. 1991;337:1299–1304
  8. Rosman JB, Langer K, Brandl M, et al. Protein-restricted diets in chronic renal failure: A four year follow-up shows limited indications. Kidney Int Suppl. 1989;27:S96–S102
  9. Williams PS, Stevens ME, Fass G, Irons L, Bone JM. Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure:A prospective, randomized, controlled trial. Q J Med. 1991;81:837–855
  10. Fouque D, Wang P, Laville M, Boissel JP. Low protein diets delay end-stage renal disease in non diabetic adults with chronic renal failure. Cochrane Database Syst Rev. 2000;CD001892
  11. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease (Modification of Diet in Renal Disease Study Group). N Engl J Med. 1994;330:877–884
  12. Levey AS, Greene T, Sarnak MJ, et al. 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. Am J Kidney Dis. 2006;48:879–888
  13. Brunori G, Viola BF, Parrinello G, et al. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: A prospective randomized multicenter controlled study. Am J Kidney Dis. 2007;49:569–580
  14. Rabbat CG. Review: A low-protein diet delays end-stage renal disease or death in stage 3 to 5 chronic kidney disease. ACP J Club. 2006;145:64
  15. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–2653
  16. Rosborough TK, Bank CH, Cummings MK, Phillips PP, Pierach CA. MRFIT after 10.5 years. JAMA. 1990;264:1534–1535
  17. Sarnak MJ, Greene T, Wang X, et al. The effect of a lower target blood pressure on the progression of kidney disease: Long-term follow-up of the Modification of Diet in Renal Disease Study. Ann Intern Med. 2005;142:342–351
  18. Beck GJ, Berg RL, Coggins CH, et al. Design and statistical issues of the Modification of Diet in Renal Disease trial (The Modification of Diet in Renal Disease Study Group). Control Clin Trials. 1991;12:566–586
  19. Klahr S. Role of dietary protein and blood pressure in the progression of renal disease. Kidney Int. 1996;49:1783–1786
  20. Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985;27:58–65
  21. Metropolitan life Insurance Company. Metropolitan height and weight tables. Stat Bull. 1983;64:1–9
  22. Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996;27:652–663
  23. Curb JD, Ford CE, Pressel S, et al. Ascertainment of vital status through the National Death Index and the Social Security Administration. Am J Epidemiol. 1985;121:754–766
  24. Hunsicker LG, Adler S, Caggiula A, et al. Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int. 1997;51:1908–1919
  25. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: A meta-analysis. Ann Intern Med. 1996;124:627–632
  26. Kasiske BL, Lakatua JD, Ma JZ, Louis TA. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis. 1998;31:954–961
  27. Pollock CA, Ibels LS, Zhu FY, et al. Protein intake in renal disease. J Am Soc Nephrol. 1997;8:777–783
  28. Pollock CA, Ibels LS, Allen BJ, et al. Total body nitrogen as a prognostic marker in maintenance dialysis. J Am Soc Nephrol. 1995;6:82–88
  29. Vendrely B, Chauveau P, Barthe N, et al. Nutrition in hemodialysis patients previously on a supplemented very low protein diet. Kidney Int. 2003;63:1491–1498
  30. Avram MM, Mittman N, Bonomini L, Chattopadhyay J, Fein P. Markers for survival in dialysis: A seven-year prospective study. Am J Kidney Dis. 1995;26:209–219
  31. Bergstrom J, Lindholm B. Malnutrition, cardiac disease, and mortality: An integrated point of view. Am J Kidney Dis. 1998;32:834–841
  32. Kopple JD. Effect of nutrition on morbidity and mortality in maintenance dialysis patients. Am J Kidney Dis. 1994;24:1002–1009
  33. Menon V, Greene T, Wang X, et al. C-Reactive protein and serum albumin as predictors of all-cause and cardiovascular mortality in patients with chronic kidney disease. Kidney Int. 2005;68:772–776
  34. Heymsfield SB, Arteaga C, McManus C, Smith J, Moffitt S. Measurement of muscle mass in humans: Validity of the 24-hour urinary creatinine method. Am J Clin Nutr. 1983;37:478–494
  35. Walser M. Creatinine excretion as a measure of protein nutrition in adults of varying age. JPEN J Parenter Enteral Nutr. 1987;11(suppl 5):S73–S78
  36. Lucas PA, Meadows JH, Roberts DE, Coles GA. The risks and benefits of a low protein-essential amino acid-keto acid diet. Kidney Int. 1986;29:995–1003
  37. Chauveau P, Barthe N, Rigalleau V, et al. Outcome of nutritional status and body composition of uremic patients on a very low-protein diet. Am J Kidney Dis. 1999;34:500–507
  38. Chauveau P, Vendrely B, El Haggan W, et al. Body composition of patients on a very low-protein diet: A two-year survey with DEXA. J Ren Nutr. 2003;13:282–287
  39. Kopple JD, Levey AS, Greene T, et al. Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study. Kidney Int. 1997;52:778–791
  40. Kopple JD, Monteon FJ, Shaib JK. Effect of energy intake on nitrogen metabolism in nondialyzed patients with chronic renal failure. Kidney Int. 1986;29:734–742
  41. Rigalleau V, Combe C, Blanchetier V, et al. Low protein diet in uremia: Effects on glucose metabolism and energy production rate. Kidney Int. 1997;51:1222–1227
  42. Mehrotra R, Nolph KD. Treatment of advanced renal failure: Low-protein diets or timely initiation of dialysis?. Kidney Int. 2000;58:1381–1388
  43. Aoyama I, Niwa T. An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats. Am J Kidney Dis. 2001;37(suppl 2):S7–S12
  44. Kopple J. Nutritional Management of Renal Disease. (ed 2). Baltimore: Lippincott Williams & Wilkins; 2003;
  45. Niwa T, Ise M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med. 1994;124:96–104
  46. Niwa T, Tsukushi S, Ise M, et al. Indoxyl sulfate and progression of renal failure: Effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients. Miner Electrolyte Metab. 1997;23:179–184
  47. Sanaka T, Sugino N, Teraoka S, Ota K. Therapeutic effects of oral sorbent in undialyzed uremia. Am J Kidney Dis. 1988;12:97–103
  48. Teschan PE, Beck GJ, Dwyer JT, et al. Effect of a ketoacid-aminoacid-supplemented very low protein diet on the progression of advanced renal disease: A reanalysis of the MDRD feasibility study. Clin Nephrol. 1998;50:273–283
  49. Menon V, Wang X, Sarnak MJ, et al. Long-term outcomes in nondiabetic chronic kidney disease. Kidney Int. 2008;73:1310–1315

 Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Paul Muntner, PhD, MHS, Mount Sinai School of Medicine) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

 Originally published online as doi:10.1053/j.ajkd.2008.08.009 on October 28, 2008.

PII: S0272-6386(08)01297-3

doi: 10.1053/j.ajkd.2008.08.009

American Journal of Kidney Diseases
Volume 53, Issue 2 , Pages 208-217 , February 2009

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