The Modification of Diet in Renal Disease Study: design, methods, and results from the feasibility study.

The Modification of Diet in Renal Disease (MDRD) Study is a multicenter clinical trial designed to assess acceptance, safety, and efficacy of restricted protein and phosphorus diets in patients with progressive renal disease. The Feasibility Study was designed to test procedures and recruitment strategies and to estimate sample size for the Full-Scale Trial. The Feasibility Study was not designed to compare rates of progression of renal disease among diet groups. Patients aged 18 to 75 years, with a glomerular filtration rate (GFR; measured by 125I-iothalamate clearance) between 7.5 and 80 mL/min/1.73 m2, and a previous progressive increase in serum creatinine, were eligible for enrollment. Compliance with prescribed dietary protein intake was calculated from urea nitrogen appearance (UNA). Nutritional status was monitored by anthropometry and serum proteins. Progression of renal disease was calculated as the rate of decline of GFR. Ninety-six patients met all of the eligibility requirements and were randomized to study diets. Follow-up was conducted for a mean duration of 14 months (range, 2 to 22 months). Although most patients did not achieve the prescribed protein intake, marked changes in intake were observed among patients assigned to the low-protein diets, and mean estimated protein intake differed significantly among diet groups. No patients became malnourished. Mean rates of decline in GFR were relatively slow, and variability among individuals was high. As expected, the number of patients enrolled was too small to determine if the rate of decline in GFR was significantly slower among patients assigned to the restricted protein and phosphorus diets. The rate of decline in GFR was significantly inversely correlated with long-term average mean arterial blood pressure (MAP), even among patients whose blood pressure was controlled to levels within the normal range. However, because patients were not randomly assigned blood pressure goals, it was not possible to determine whether a causal relationship exists. Based on the experience gained during the Feasibility Study, the design for the Full-Scale Study includes two studies of defined by patients' baseline levels of renal function. Within each study, patients will be assigned randomly to one of two diets, and within each diet group, to one of two levels of blood pressure control. Based on variability of rates of decline in GFR slopes observed during the Feasibility Study, 800 patients with follow-up periods of up to 4 years will be required for the Full-Scale Trial.