The effect of protein restriction on the progression of renal insufficiency. Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications. Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus. Metabolic effects of two low protein diets in chronic kidney disease stage 4-5--a randomized controlled trial. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood.
Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure. Several retrospective and prospective studies confirmed the beneficial effect of dietary protein restriction (DPR) on the downhill course of renal function in chronic kidney disease. The long-term results of this therapeutic modality may be different than the short-term effects. In our nephrology outpatient department, a prospective randomized trial has been in progress since April, 1982. In 1984, we reported a general beneficial effect of our diet after two years of follow-up. Two hundred and forty-eight patients with initial creatinine clearances between 10 and 60 ml/min entered the trial. Patients were stratified for sex, age and degree of renal insufficiency. One hundred and twenty-nine patients were randomly assigned to a DPR-group (0.4 to 0.6 g/kg/day); 118 patients to a control group. Patients on DPR visited the dietitian every three months during the first 24 months of the study; thereafter, as with the controls, the dietitian visits were only for specific needs. Urea excretion decreased significantly in DPR patients as a sign of good compliance and stayed at that level, even without frequent visits to the dietitian. Biochemical parameters showed no signs of malnutrition. Amino acid profiles were related to the degree of renal failure. The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet. Furthermore, there were striking intersex differences. Males showed a more rapid decline towards end-stage renal failure, but responded in a positive way to the diet, whereas female patients did not benefit from the dietary manipulation at all.(ABSTRACT TRUNCATED AT 250 WORDS) Recent data suggest that dietary protein restriction improves survival and delays the progression to end-stage renal disease (ESRD) in non-diabetic nephropathies. The purpose of our study was to determine the effect of dietary protein restriction on survival and progression to ESRD in diabetic nephropathy.
                A four-year prospective, controlled trial with concealed randomization was performed comparing the effects of a low-protein diet (0.6 g/kg/day) with a usual-protein diet. The study included 82 type 1 diabetic patients with progressive diabetic nephropathy [pre-study mean decline in glomerular filtration rate (GFR) 7.1 mL/min/year (95% CI, 5.8 to 8.5)]. The main outcome measures were decline in GFR and development of ESRD or death.
                During the follow-up period the usual-protein diet group consumed 1.02 g/kg/day (95% CI; 0.95 to 1.10) as compared with 0.89 (0.83 to 0.95) in the low-protein diet group (P = 0.005). The mean declines in GFR were 3.9 mL/min/year (2.7 to 5.2) in the usual-protein diet group and 3.8 (2.8 to 4.8) in the low-protein diet group. ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% on a low-protein diet (log-rank test; P = 0.042). The relative risk of ESRD or death was 0.23 (0.07 to 0.72) for patients assigned to a low-protein diet, after an adjustment at baseline for the presence of cardiovascular disease (P = 0.01). Blood pressure and glycemic control were comparable in the two diet groups during the follow-up period.
                Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment. Restriction of dietary protein may slow the progression of renal failure in diverse renal diseases, but the extent to which such a diet is beneficial in patients with diabetic nephropathy is uncertain.
                We studied the effect of reduced intake of protein and phosphorus on the progression of renal disease in 35 patients with insulin-dependent (Type I) diabetes mellitus and clinically evident nephropathy. The low-protein, low-phosphorus diet contained 0.6 g of protein per kilogram of ideal body weight per day, 500 to 1000 mg of phosphorus, and 2000 mg of sodium. The control diet consisted of the patient's prestudy diet with the stipulation that it contain 2000 mg of sodium and at least 1 g of protein per kilogram per day and 1000 mg of phosphorus. Renal function was assessed by measurement of iothalamate and creatinine clearances at intervals of 3 to 6 months, and the patients were followed for a minimum of 12 months (mean, 34.7). The declines in mean glomerular filtration rates were compared between groups by linear-regression analysis of the glomerular filtration rate as a function of time.
                The patients who followed the study diet for a mean of 37.1 months had declines in iothalamate clearance of 0.0043 ml per second per month and in creatinine clearance of 0.0055 ml per second per month. The comparable values in the control group were 0.0168 and 0.0135, respectively (P less than 0.05). Blood pressure was well controlled, and the degree of glycemic control was comparable in both groups.
                Dietary restriction of protein and phosphorus can retard the progression of renal failure in patients with Type I diabetes mellitus who have nephropathy. We believe that wider use of this treatment is indicated. International guidelines have not reached a complete agreement about the optimal amount of dietary proteins in chronic kidney disease(CKD). The aim of this study was to compare, with a randomized-controlled design, the metabolic effects of two diets with different protein content (0.55 vs 0.80 g/kg/day) in patients with CKD stages 4-5.
                Study design and sample size calculations were based on previously published experience of our group with low protein diet. The primary outcome of the study was the modification of serum urea nitrogen concentration. From 423 patients randomly assigned to the two diets 392 were analysed: 200 for the 0.55-Group and 192 for the 0.8-Group. The follow-up ranged 6-18 months.
                Mean age was 61+/-18 years, 44% were women, mean eGFR was 18+/-7 ml/min/month. Three months after the dietary assignment and throughout the study period the two groups had a significantly different protein intake (0.72 vs 0.92 g/kg/day). The intention-to-treat analysis did not show any difference between the two groups. Compliance to the two test diets was significantly different (P < 0.05): 27% in the 0.55-Group and 53% in the 0.8-Group, with male gender and protein content (0.8 g/kg/day) predicting adherence to the assigned diet. The per protocol analysis, conversely, showed that serum urea nitrogen, similar at the time of randomization, significantly increased in the 0.8-Group vs 0.55-Group by 15% (P < 0.05). Serum phosphate, PTH and bicarbonate resulted similar in the two groups throughout the study. The 24 h urinary urea nitrogen significantly decreased after the first 3 months in 0.55-Group (P < 0.05), as well as the excretion of creatinine, sodium and phosphate (P < 0.05 vs baseline) and were significantly lower than the 0.8-Group. The prescription of phosphate binders, allopurinol, bicarbonate supplements and diuretics resulted significantly less frequent in the 0.55-Group (P < 0.05).
                This study represents the first evidence that in CKD patients a protein intake of 0.55 g/kg/day, compared with a 0.8 g/kg/day, guarantees a better metabolic control and a reduced need of drugs, without a substantial risk of malnutrition. Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF.
                A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study.
                The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year.
                A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.
Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 32% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.