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Therapeutics

Dietary protein and blood pressure intervention failed to slow renal disease progression

ACP J Club. 1994 Sept-Oct;121:46. doi:10.7326/ACPJC-1994-121-2-046

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• Letter: Dietary protein and blood pressure intervention failed to slow renal disease progression


Source Citation

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. Mar 1994


Abstract

Objective

To determine the effectiveness of restricting protein intake and controlling blood pressure (BP) in delaying the progression of renal disease in patients with various chronic conditions.

Design

2 randomized controlled trials with a mean follow-up of 2.2 years.

Setting

Multicenter study.

Patients

585 patients with glomerular filtration rates (GFRs) of 25 to 55 mL/min per 1.73 m2 of body surface area in study 1. 255 patients with GFRs of 13 to 24 mL/min per 1.73 m2 in study 2. Inclusion criteria were age 18 to 70 years, serum creatinine concentrations of 1.2 to 7.0 mg/dL in women and 1.4 to 7.0 mg/dL in men or a creatinine clearance of < 1.17 mL/s per 1.73 m2 (< 70 mL/min per 1.73 m2), and a mean arterial pressure (MAP) of ≤ 125 mm Hg. Exclusion criteria were pregnancy, body weight < 80% or > 160% of standard body weight, diabetes mellitus requiring insulin therapy, proteinuria > 10 g/d, suspected noncompliance, previous renal transplantation, or chronic medical conditions.

Intervention

In study 1, patients were allocated to a usual- or a low-protein diet (1.3 or 0.58 g protein/kg of body weight per day) and to a usual- or a low-BP group (MAP ≤ 107 or ≤ 92 mm Hg). In study 2, patients were allocated to a low- or a very-low-protein diet (0.58 or 0.28 g) with keto acid-amino acid supplementation and a usual- or low-BP group (same as study 1).

Main Outcome Measures

Rate of decline in GFR, occurrence of end-stage renal disease, and death.

Main Results

In study 1, the low-protein and low-BP groups had a more rapid decline in GFR during the first 4 months and a slower decline thereafter when compared with the usual-protein group and the usual-BP group. The treatment groups did not differ for projected 3-year decline in GFR (11.5 mL/min per 3 years, all groups combined). In study 2, neither intervention significantly slowed the decline in GFR. No delays occurred in time to end-stage renal disease or death in either study.

Conclusion

Protein restriction and blood pressure control did not slow the decline in glomerular filtration rates in patients with moderate-to-severe chronic renal disease.

Sources of funding: National Institute of Diabetes and Digestive and Kidney Diseases and the Health Care Financing Administration.

For article reprint: MDRD Study Data Coordinating Center, Department of Biostatistics and Epidemiology, P88, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. FAX 314 45 5110.


Commentary

The Modification of Diet in Renal Disease study was born of the desire to beneficially intervene in the otherwise inexorable course of chronic renal failure. Data from the basic science arena and preliminary clinical studies have suggested that dietary protein restriction and BP control might prove successful in delaying the progression of chronic renal disease.

This study was designed to test 2 basic interventions: protein and phosphorous restriction and BP control. Their effect on the GFR was assessed by iothalamate clearance, a marker superior to serum creatinine level or creatinine clearance particularly in persons whose protein is restricted. The patient sample has the typical symptoms of chronic renal failure seen by internists and nephrologists if most patients with diabetic nephropathy are excluded; 25% of patients had polycystic kidney disease, 25% had glomerulopathies, and most of the remainder had tubulointerstitial diseases or unknown conditions.

Interpretation of the results by the intention-to-treat model showed no beneficial effect of either intervention. A faster decline in GFR during the first 4 months in the intervention groups markedly complicated the interpretation of the data. A plethora of subgroup analyses and reinterpretations of the data likely will be seen in the future, each with its own attendant problems.

Is there something that can be salvaged from this negative study? Subgroup analysis showed that patients with 24-hour protein excretion levels > 1 g benefited from BP reduction to a MAP of 92 mm Hg (for example, approximately 128/74 mm Hg), a level considerably lower than Joint National Committee recommendations. Because of the safety of careful BP reduction to the level shown in this sample of patients, it may be reasonable to attempt similar BP control in patients with chronic renal failure who have 24-hour protein excretion levels of > 1 g but who are not diabetic. Confirmation of this and other subgroup observations by clinical trial or meta-analysis is the next step.

David L. Harvey, MD
Piedmont Nephrology and Hypertension Associates Hickory, North Carolina, USA