Meta-analysis: Dietary protein restriction delays progression in renal disease
ACP J Club. 1996 July-Aug;125:18. doi:10.7326/ACPJC-1996-125-1-018
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 April 1;124: 627-32. [PubMed ID: 8607590]
To determine the efficacy of dietary protein restriction in delaying progression of chronic renal disease in patients with and without diabetes by using meta-analysis.
Studies were identified by searching MEDLINE (1966 to 1994) and by reviewing the bibliographies of published review articles and studies.
Studies were selected if they were published, randomized, controlled trials or cross-over studies of low-protein diet in patients with nondiabetic renal disease or insulin-dependent diabetes mellitus (IDDM). For studies of nondiabetic renal disease, follow-up had to be > 1 year and include data on the number of patients who developed renal failure or died. For the studies of IDDM, follow-up had to be > 9 months in length and include data on the change in glomerular filtration rate or degree of albuminuria.
Extracted data included number of patients, length of follow-up, protein intake of the prescribed diet, and the level of renal function (glomerular filtration rate, creatinine clearance level, serum creatinine level, and urinary albumin excretion rate). The cause of renal failure in nondiabetic patients was not available. Data were extracted by 2 independent reviewers.
5 randomized controlled trials (a total of 1413 patients with nondiabetic renal disease) that tested a protein intake of 0.4 to 0.6 g/kg of body weight per day and 5 studies (a total of 108 patients with IDDM) that tested a protein intake of 0.5 to 0.85 g/kg of body weight per day met the selection criteria. The pooled results of the studies of nondiabetic renal disease showed a reduced risk for renal failure or death in patients who had a protein-restricted diet compared with those who had a usual protein diet (relative risk [RR] 0.67, 95% CI 0.50 to 0.89, P = 0.007). The pooled results of the studies of IDDM showed a reduced risk for progression in renal disease (a decline in glomerular filtration rate or creatinine clearance level or an increase in urinary albumin excretion rate) among patients who had a protein-restricted diet compared with those who had a usual diet (RR 0.56, CI 0.40 to 0.77, P < 0.001). The beneficial effects of protein restriction were unrelated to change in blood pressure or glycemic control.
Dietary protein restriction reduces the risk for renal failure or death in nondiabetic renal disease and improves nephropathy in insulin-dependent diabetes mellitus.
Source of funding: University of California, Irvine.*
For article reprint: Dr. P.H. Wang, Department of Medicine, Medical Science I, C240, University of California, Irvine, CA 92717, USA. FAX 714-824-2200.
*Information supplied by author.
End-stage renal disease is a source of frustration for nephrologists. Since the 1940s, low-protein diets have been prescribed to reduce uremic symptoms, and results from numerous recent studies, mostly uncontrolled, suggest that reducing protein intake can slow the so-called "natural" progression of renal disease toward end-stage renal failure. In this meta-analysis, Pedrini and colleagues used a robust renal event that could be easily observed in all trials (i.e., "renal death"—death or the need to start dialysis or transplant a kidney). Introduced in the early 1990s (1), this outcome is unusual for nephrologists to use. They generally use serum creatinine level or glomerular filtration rate measurements for the follow-up of patients with renal disease. The apparently conflicting results from this meta-analysis and from the Modification of Diet in Renal Disease (MDRD) study (2) may reflect the use of different outcome criteria. The trend for a beneficial effect of low-protein diets in slowing progression to renal failure, however, is apparent in this meta-analysis that uses the renal death outcome and is also reported for the decline in the glomerular filtration rate in the second part of the MDRD study (2). More recently, secondary analyses from the MDRD study have balanced the initial study conclusions toward a more beneficial effect of low-protein diets (3). Furthermore, the number of patients to be treated (NNT) by a low-protein diet to spare 1 extra renal death/year was recently estimated to range from 4 to 50 (4). For primo-secondary prevention, this NNT range compares favorably with the effects of statins in the 4S or Woscops trials (4). Thus, these data strongly suggest that low-protein diets should be recommended for nondiabetic patients with chronic renal failure.
The evidence for patients with insulin-dependent diabetes and chronic renal failure, however, is less robust. As emphasized by the authors, data were available for only a few patients, follow-up was shorter, and not all the trials were randomized. 2 important potentially confounding factors were identified—receiving angiotensin-converting enzyme (ACE) inhibitors and glycemic control—but these were well balanced between the groups.
Precautions should be taken against diets becoming hypocaloric in these frail patients when protein intake is reduced. Addition of the nephroprotective agents ACE inhibitors to low-protein diets, with appropriate monitoring, is highly recommended. Based on the MDRD study (2), this may postpone the need for dialysis by > 2 years (5).
Denis Fouque, MD, PhD
Hôpital Edouard Herriot and Université Claude BernardLyon, France
2. 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;330:877-84.
3. Levey AS, Greene T, Beck GJ, et al. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J Am Soc Nephrol. 1999;10:2426-39.