The effect of protein restriction on the progression of renal insufficiency. Metabolic effects of two low protein diets in chronic kidney disease stage 4-5--a randomized controlled trial. Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure. Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications. Effects of severe protein restriction with ketoanalogues in advanced renal failure. Effects of a supplemented hypoproteic diet in chronic kidney disease.
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. 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. The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure (CRF).
                We monitored for 2 years the erythropoietin (EPO) requirement in patients with advanced CRF (creatinine clearance < or =25 mL/min), randomized to either low protein diet (LPD) group (0.6 g/kg body weight/day, N = 10) or very low protein diet (VLPD) group (0.3 g/kg body weight/day, N = 10) supplemented with a mixture of ketoanalogs and essential amino acids, both kept at target hemoglobin levels.
                The achieved protein intake after 6 months was 0.79 +/- 0.02 g/kg body weight/day and 0.50 +/- 0.02 g/kg body weight/day in LPD and VLPD, respectively; such a difference was maintained up to the end of follow up. The final hemoglobin values did not differ from the basal values in either group (11.5 +/- 0.2 g/dL and 11.5 +/- 0.3 g/dL). EPO dose, that was similar at baseline (62.4 +/- 9.6 UI/kg body weight/week and 61.8 +/- 8.8 UI/kg body weight/week subcutaneously), remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 +/- 7.0 UI/kg body weight/week (P < 0.0001 vs. basal and LPD). VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate; however, EPO requirement was not correlated with the changes of these parameters. On the contrary, the variation of EPO dose directly correlated with the modification of parathyroid hormone (PTH) levels, that diminished from 229 +/- 55 pg/mL to 118 +/- 16 pg/mL (P < 0.0001) in VLPD and did not change in LPD.
                In patients with advanced CRF, an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35% of the EPO dose required to maintain the target hemoglobin levels. This effect appears dependent on the correction of a moderate secondary hyperparathyroidism. 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) To compare a severe protein restriction diet supplemented with ketoanalogues to a moderate protein restriction diet in order to limit glomerular filtration rate (GFR) decrease in an advanced renal insufficiency stage.
                Prospective randomised study conducted to compare a severe protein restriction diet (0.30 g/kg/day) supplemented with a preparation of ketoanalogues, hydroxyanalogues of aminoacids and aminoacids (Group A) to a moderate protein restriction diet (0.65 g/kg/day) (Group B).
                50 uremic patients included (25 in each group) with GFR is <20 mL/min/1.73m2.
                There were no statistically significant differences between the two dietary regimens for the renal survival. But uremia decreased significantly in Group A (22.7+/-5.2 to 18.5+/-6.7 mmol/L) and increased in Group B (26.8+/-9.0 to 34.9+/-9.9 mmol/L). Calcemia increased in Group A from 2.28+/-0.18 to 2.42+/-0.17 mmol/L, p<0.01 with a stable phosphoremia while calcemia decreased in Group B (2.33+/-0.18 to 2.25+/-0.17 mmol/L, p<0.05). At the end of the study, Group A was different from Group B for calcemia (2.42+/-0.17 vs. 2.25+/-0.17 mmol/L, p<0.01), phosphoremia (1.39+/-0.30 vs. 1.80+/-0.65 mmol/L, p<0.02), alkaline phosphatase (61.42+/-22.93 vs. 78.8+/-27.0, p<0.05) and parathormone plasma levels (2.71+/-1.55 vs. 5.91+/-1.41 ng/mL, p<0.001).
                Compared to a moderate protein restriction (0.65 g/kg/day), a severe protein restriction (0.3 g/kg/day) supplemented by ketoanologues does not limit GFR decrease when GFR is below 20 mL/min/1.73m2, but improves phosphocalcic plasma parameters. We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD).
                We performed a prospective, open-label, parallel, randomized, controlled trial.
                The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania.
                A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups.
                Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d).
                Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline.
                In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted.
                SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD.
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.