Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years (mean±SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n=30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n=32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 μmol/1, plasma phosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19±3 months. Mean plasma creatinine rose from 398±33 to 600±50 μmol/1. Dietary protein intake was estimated at 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05 in the low phosphate and 1.14±0.05 in the controls, phosphate intake was 815±43, 1000± 47, and 1315±57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p<0.01) only in those on protein restriction, at 213±9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p<0.05) in both the low protein group (17.9±0.8 mmol/24 hours) and the low phosphate group (18.6±1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89±3/1 (low protein), 148/87±3/1 (low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall of creatinine clearance (ml/min/ 1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression (‘breakpoint’) analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56±0.08 ml/min/1.73 m2/month (low protein, n=28), 0.44±0.07 (low phosphate, n=23) and 0.69±0.11 (control, n=27). In 50 patients (18 low protein, 16 low phosphate and 16 control) whose rate of progression could be calculated before and after randomization, there was a fall in rate of progression averaging 0.18 ml/min/1.73 m2/month in those on low protein diet and those on low phosphate diet, but a rise of 0.08 in the controls. These differences were, however, not statistically significant. Similar results were obtained when the rates of deterioration were calculated from plasma creatinine. Significant individual improvements (p<0.01) in rates of progression by ‘breakpoint’ analysis occurred in 17 patients: six on low protein, seven on low phosphate and in four controls. Sixty-one (72 per cent) of the patients examined by this method showed no significant change in the rate of progression while seven patients had accelerated progression. There was no difference in the requirement for maintenance dialysis facilities between groups. No significant benefit of protein and phosphate restriction was therefore demonstrated.