Correspondence
Dietary Protein Restriction and Blood-Pressure Control in Chronic Renal Insufficiency
N Engl J Med 1994; 331:405-406August 11, 1994
- Article
To the Editor:
The long-awaited report of the Modification of Diet in Renal Disease Study Group, presented by Klahr et al. (March 31 issue),1 lacks some key information needed to interpret the results, particularly those of study 1, which showed small benefits of moderate restriction of dietary protein and a lower blood pressure. There should have been a table providing information about the patients' age, sex, and body-mass index and the distribution of underlying renal diseases. Although this information is available elsewhere,2,3 I and no doubt many other readers would have liked to see it in the paper1.
3 ReferencesJacob Lemann, Jr., M.D.
Medical College of Wisconsin, Milwaukee, WI 532261
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. N Engl J Med 1994;330:877-884
Full Text | Web of Science | Medline2
Kusek JW ,Coyne T ,de Velasco A , et al. Recruitment experience in the full-scale phase of the Modification of Diet in Renal Disease Study. Control Clin Trials 1993;14:538-557
CrossRef | Medline3
Greene T ,Bourgoignie JJ ,Habwe V , et al. Baseline characteristics in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol 1993;3:1819-1834
Web of Science
To the Editor:
We do not agree with the conclusion of Klahr et al. that a low-protein diet and blood-pressure control have only a limited effect on the progression of chronic renal failure. Their study has several problems. First, the proportions of patients with different types of renal disease differed from those usually encountered, in that the proportion of patients with polycystic kidney disease was high and patients with diabetes were excluded. Second, caloric intake was so low that patients may have had malnutrition. Third, the protein intake from the keto acid-amino acid supplement was not accounted for, so that the protein intake of the patients in the group with the very-low-protein diet may have been underestimated. Finally, the use of angiotensin-converting-enzyme inhibitors may have masked the benefits of the low-protein diet. Since it has been widely accepted that a low-protein diet has beneficial effects on the progression of chronic renal failure, we must be very careful about drawing a negative conclusion.
Tatsuo Shiigai, M.D.
Toride Kyodo General Hospital, Toride, Ibaraki 301, JapanHiroshi Nonoguchi, M.D.
Kimio Tomita, M.D.
Tokyo Medical and Dental University, Tokyo 113, JapanTo the Editor:
The fact that no significant benefit was demonstrated for low-protein diets with respect to delaying the progression of renal disease in the Modification of Diet in Renal Disease Study is of great importance. Low-protein diets have become accepted as an important component of the treatment of patients with renal insufficiency, despite a dearth of supporting data from studies in human subjects. An intervention that is not entirely innocuous should not be accepted into general practice without strong evidence that it is effective.
There are several potential problems with the use of such diets. First, the change in the palatability of the diet accompanying a decrease in protein intake of the magnitude studied would decrease the quality of life for many patients. Second, it has become increasingly clear that one of the most important determinants of survival in patients undergoing dialysis is their nutritional status1. The use of low-protein diets has the potential to leave some patients severely malnourished when they begin dialysis. Third, in patients with metabolic acidosis, which is common in chronic renal insufficiency, low-protein diets lead to muscle breakdown with a resultant loss of lean body mass2.
Attempts will undoubtedly be made to discount the negative results of this study. Therapy with angiotensin-converting-enzyme inhibitors in many patients in all the study groups may explain the relatively slow progression of disease in all groups, so that the low-protein diet provided little additional benefit (since its probable mechanism of action is the same as that of angiotensin-converting-enzyme inhibitors). Since the therapy with these drugs is a far simpler (and better tolerated) intervention than low-protein diets, such diets should not be used in an effort to delay the progression of renal disease.
2 ReferencesSteven Fishbane, M.D.
Winthrop-University Hospital, Mineola, NY 110511
Lowrie EG ,Lew NL . Commonly measured laboratory variables in hemodialysis patients: relationships among them and to death risk. Semin Nephrol 1992;12:276-283
Web of Science | Medline2
Williams B ,Hattersley J ,Layward E ,Walls J . Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia. Kidney Int 1991;40:779-786
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: In studies 1 and 2 the mean ages of the patients were 52 and 51 years, respectively, the percentages of men 61 and 59 percent, and the body-mass indexes 27.7 and 25.9. The renal disorders included glomerular diseases, 24 and 26 percent, respectively; polycystic kidney disease, 24 and 23 percent; and other conditions, 52 and 51 percent1.
That the proportion of patients with polycystic kidney disease was higher than usual in relation to the population with end-stage renal disease was due partly to their more frequent referral. When patients with polycystic kidney disease were excluded from analysis, the benefit of lowering blood pressure was a 26 percent less steep decline in the glomerular filtration rate (P = 0.04) in study 1, and the trend was similar in study 2. This difference is related to the greater effect of lowering the blood pressure in patients with more severe proteinuria at base line. The mean base-line urinary protein excretion was lower in the patients with polycystic kidney disease than in the remaining patients in both studies. There were no significant differences in the effect of diet among patients with different base-line levels of proteinuria or renal disorders.
As in practice, a large fraction of patients in our study were treated with inhibitors of angiotensin-converting enzyme. We cannot exclude the possibility that the use of these drugs affected the rate of progression of renal disease, but there was no difference between the diet groups in the proportion of patients who were taking the drugs during either study 1 or study 2.
If the amino acids in the keto acid-amino acid supple ment are included as a source of nitrogen, the mean estimated total protein intake (from food and the supplement) during follow-up was 0.73 and 0.66 g per kilogram per day in the patients assigned to the low-protein diet and those assigned to the very-low-protein diet, respectively, in study 2 (P<0.001). In a correlation analysis combining both groups and controlling for base-line factors that were associated with faster disease progression, a higher total protein intake was associated with more rapid progression. This finding suggests that compliance with a low-protein diet slows the progression of renal disease in patients with glomerular filtration rates below 25 ml per minute per 1.73 m2, and corroborates the findings of Ihle et al.2
We acknowledge the importance of malnutrition in patients with end-stage renal failure. We found no relation between protein intake during follow-up and the long-term rate of change in weight, arm muscle area, percentage of body fat, or serum albumin, transferrin, or cholesterol concentrations.
2 ReferencesSaulo Klahr, M.D.
Washington University Medical Center, St. Louis, MO 63178Andrew S. Levey, M.D.
New England Medical Center, Boston, MA 02111Gerald J. Beck, Ph.D.
Cleveland Clinic Foundation, Cleveland, OH 441951
Greene T ,Bourgoignie JJ ,Habwe V , et al. Baseline characteristics in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol 1993;4:1221-1236
Web of Science | Medline2
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
Full Text | Web of Science | Medline
