Modification of Diet in Renal Disease Study - MDRD

Description:

Study of low protein diet and blood pressure lowering to slow the progression of renal disease.

Hypothesis:

The study tested the hypotheses that two interventions -- a reduction in dietary protein and phosphorus intake and the maintenance of blood pressure at a level below that usually recommended -- retard the progression of renal disease and that these interventions are safe and acceptable to patients for long-term use

Study Design

Study Design:

Patients Enrolled: 840
Mean Follow Up: 2.2 years mean
Mean Patient Age: 52
Female: 40

Patient Populations:

Age 18 to 70 years Serum creatinine concentration of 1.2 to 7.0 mg per deciliter in women and 1.4 to 7.0 mg per deciliter in men or a creatinine clearance of less than 70 ml per minute per 1.73 m2 of body-surface area Mean arterial pressure of 125 mm Hg or less Normotensive patients were included in the study, and evidence of a progressive decline in the glomerular filtration rate was not required for enrollment. Patients were eligible for study 1 or 2 on the basis of their glomerular filtration rate.

Exclusions:

Pregnancy Body weight under 80 percent or over 160 percent of standard body weight Diabetes mellitus requiring insulin therapy Urinary protein excretion exceeding 10 g per day History of renal transplantation or chronic medical conditions Doubts about compliance

Primary Endpoints:

The rate of change in the glomerular filtration rate

Drug/Procedures Used:

In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients

Principal Findings:

In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate.

Interpretation:

Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease.

References:

NEJM 330:877-884.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Diet

Keywords: Follow-Up Studies, Kidney Function Tests, Kidney Failure, Chronic, Dietary Proteins, Body Weight, Blood Pressure, Proteinuria, Creatinine, Keto Acids, Diet, Protein-Restricted, Glomerular Filtration Rate, Phosphorus


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