Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure. Severe dietary protein restriction in overt diabetic nephropathy: benefits or risks? Reduced albuminuria after dietary protein restriction in insulin-dependent diabetic patients with clinical nephropathy. Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Effect of moderate dietary protein restriction on the progression of overt diabetic nephropathy: a 6-mo prospective study. Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension. Nutritional treatment of renal failure in type 1 diabetic nephropathy. Effect of dietary protein restriction on functional renal reserve in diabetic nephropathy. Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus. Protein restriction, glomerular filtration rate and albuminuria in patients with type 2 diabetes mellitus: a randomized trial.
To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen.
                Prospective, randomized case-control clinical trial.
                Nephrology outpatients.
                A total of 169 patients, 89 affected with CRF and chronic hypertension and 80 affected with overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes) and chronic hypertension.
                Diabetic patients and nondiabetic patients were randomly divided into 2 groups: 40 diabetic patients received a low-protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet; similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and 45 were maintained on a free protein diet. The investigation lasted 1 year.
                Renal function and nutritional status.
                At the end of the study, there were no statistically significant differences in renal function between treated and nontreated diabetic patients, whereas treated nondiabetic patients showed a lower decrease in renal function compared with the nontreated group. In both diabetic and nondiabetic patients, the mean body weight and obesity index decreased significantly in treated patients compared with nontreated ones. Serum albumin and prealbumin were stable in all patients during the whole study time, and there were no other signs of malnutrition.
                An adequate dietary protein restriction is accepted by patients, and it is well tolerated during a 12-month follow-up. Without any sign of malnutrition, it is possible to get near the ideal body weight and to reduce the obesity index and the body mass index, which are both well-established risk factors for developing cardiovascular pathology. In nondiabetic patients only, we observed a significant slowing of the progression of renal damage. To evaluate whether restricting protein intake may delay the progression of chronic renal failure caused by overt diabetic nephropathy and also whether this increases the risk of malnutrition.
                Prospective clinical trial.
                Nephrology outpatients.
                Sixty-nine patients (32 affected by type 1 and 37 by type 2 diabetes, all treated with insulin) affected by both overt diabetic nephropathy and hypertension.
                The study was started once hypertension and glycemia had been under control for at least 3 months. Two groups of patients, matched for similar mean glomerular filtration rate value and nutritional status, were studied: a low-protein diet (0.6 g/kg/d) was randomly prescribed to 35 patients, whereas in the other 34 patients a free diet intake was maintained for 12 months.
                Renal function and nutritional status.
                The protein intake was significantly different in the 2 groups of patients, whereas the average decline of glomerular filtration rate during the follow-up was comparable. In the low-protein diet group, serum prealbumin concentration significantly decreased after 9 months, whereas serum albumin decreased at the end of the study.
                Severe dietary protein restriction does not seem to delay the progression of renal disease in patients with overt diabetic nephropathy, whereas it may induce malnutrition.
                Copyright 2002 by the National Kidney Foundation, Inc. Recent clinical investigations have demonstrated that an early restriction of dietary protein intake may reduce the rate of progression of chronic renal failure in humans. In this study the effects of a restricted-protein diet on kidney function in type I diabetic patients with clinical nephropathy were evaluated. Sixteen patients (9 men, 7 women) with mean age 37.1 +/- 9.8 yr, mean duration of diabetes 17.7 +/- 6.6 yr, proteinuria greater than 0.5 g/24 h, and serum creatinine concentration of 0.7-1.9 mg/dl were studied. Patients were randomly divided into two groups. The low-protein diet (LPD) group comprised seven patients who were kept for 4.5 +/- 1 mo on a diet containing 0.71 +/- 0.12 g X kg-1 X day-1 protein. The normal-protein diet (NPD) group comprised nine patients as controls maintained for 11.7 +/- 7 mo on their usual diabetic diet containing 1.44 +/- 0.12 g X kg-1 X day-1 protein. All patients were studied every 1-2 mo. Metabolic control was assessed by evaluation of 5-8 blood glucose determinations/day and by glycosylated hemoglobin, whereas renal function was evaluated by albumin, IgG and beta 2-microglobulin urinary excretion rates, serum creatinine concentration, and creatinine clearance. At each visit, serum concentrations of total protein, albumin, phosphate, calcium, and electrolytes and weight and blood pressure were also measured. A significant reduction (434 +/- 244 to 205 +/- 212 micrograms/min, mean +/- SD) in albumin excretion rate was found in all LPD patients after dietary protein restriction, with a significant reincrease (689 +/- 201 micrograms/min) in the same patients several months after interruption of diet.(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. To assess whether moderate dietary protein restriction can delay the progression of overt diabetic nephropathy, 22 subjects with insulin-dependent diabetes mellitus were randomly assigned to an unrestricted protein diet (> 1.6 g.kg body wt-1.d-1) or a moderately protein-restricted diet (0.8 g.kg body wt-1.d-1) and followed prospectively for six mo. Direct isotope methods were used to assess renal function. Protein intake was assessed by measurement of urinary urea nitrogen. The two groups were well-matched for age, sex, duration of diabetes, glycemic control, blood pressure, and degree of renal insufficiency. Patients consuming the unrestricted protein diet (n = 11) showed a progressive decline in glomerular filtration rate of 1.3 mL.min-1.mo-1 with no change in proteinuria. Patients consuming the moderately protein-restricted diet showed a marked decrease in the degree of proteinuria (2.15-1.13 g/d, P = 0.036) and a stabilization of glomerular filtration rate. This occurred independently of changes in blood pressure or glycemic control. Moderate dietary protein restriction can ameliorate progression of overt diabetic nephropathy. To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy.
                We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g.kg-1.day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively.
                In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g.kg-1.day-1 (P < 0.005), but only seven participants consumed < 0.8 g.kg-1.day-1. Protein intake was unaltered in the UPD group (P < 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16-83) to 30 micrograms/min (95% CI, 14-67) (P < 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13-36) (P < 0.001), which was significantly different from the 5% (95% CI, -10-22) change in the UPD group (P < 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P < 0.005), whereas prevailing MAP accelerated albuminuria (P < 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P < 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr.
                This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy. This study reports the effects of a low-protein, low-phosphorus, supplemented diet in 8 type 1 diabetics with renal failure. The rate of decline of creatinine clearance, the changes of the urinary protein loss, of total serum protein, of the daily insulin requirement, of the nutritional status and of some hormonal derangements were examined. The rate of decline of creatinine clearance decreased from 1.38 +/- 0.27 ml/min/month during a previous 15.9-month period of unrestricted protein diet, to 0.03 +/- 0.37 ml/min/month during the 17.4 months on supplemented diet. Urinary protein loss significantly decreased, and total serum protein increased. The daily insulin requirement decreased and no deterioration of the nutritional status occurred. Secondary hyperparathyroidism was partially reversed and the mild hypothyroidism corrected. A restricted protein and phosphorus diet supplemented with essential amino acids and ketoanalogs seems to exert several beneficial and no unwanted side effects in type 1 diabetics with renal failure. Functional renal reserve in patients with insulin-dependent diabetes mellitus, as determined by the glomerular filtration rate (GFR) response test, is a measure of the capacity of the kidney to increase glomerular filtration in response to the stimulus of a protein meal or amino acid infusion. This 12-month study evaluated the changes in functional renal reserve in eight patients with insulin-dependent diabetes mellitus with nephropathy (micro-albuminuria [greater than or equal to 30 micrograms/minute]) who chronically decreased their dietary protein intake to a mean of 0.6 g/kg/day (Group 1) compared with a group of similar patients (n = 7) who maintained their unusual dietary protein intake (1.0 g/kg/day, Group 2). Patients were evaluated and measurements taken at 3-, 6-, and 12-month intervals. Absolute and percent increases in GFR were calculated from three averaged 1-hour measurements after an 80-g protein test meal.
                Although the initial absolute mean rise (14 +/- 12 versus 18 +/- 13 mL/minute/1.73 m2) in GFR and maximal percent rise (16% +/- 16% versus 32% +/- 27%) after the meal did not differ significantly between the two groups, at 12 months, values in the lower protein group increased (27.8 +/- 9.5 mL/minute/1.73 m2 and 54.7% +/- 48.8%), whereas those in the normal protein intake group declined significantly (3.7 +/- 3.6 mL/min-ute/1.73 m2 and 6.5% +/- 6.5%) (p less than 0.05). Both urine urea and microalbuminuria decreased significantly (p less than 0.05) in the low protein group. Unstimulated GFR at the end of 12 months was significantly less (p less than 0.05) in Group 2 (47 +/- 2 mL/minute/1.73 m2) than in Group 1 (71 +/- 21 mL/minute/1.73 m2). The rate of decline in GFR was significantly greater (p less than 0.05) in the normal protein intake group than in the low protein intake group (0.68 +/- 0.4 versus 0.28 +/- 0.15 mL/minute/1.73 m2/month).
                This study indicates that sustained dietary protein restriction can help to preserve renal function, decrease albuminuria, and lower the baseline GFR while maintaining functional renal reserve in patients with insulin-dependent diabetes mellitus. 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. Protein restriction delays the progression of non-diabetic and type 1 diabetic renal disorders. This study assessed whether protein restriction delays the onset or early progression of renal disorders in type 2 diabetes.
                Randomized controlled trial. Outcomes were albuminuria (mg/24 h) and, as an estimate of the glomerular filtration rate, cimetidine-influenced creatinine clearance.
                Primary care.
                Patients with type 2 diabetes and microalbuminuria or at least detectable albuminuria, or a diabetes duration >5 y.
                The experimental group received dietary counselling on protein restriction (n=63); a control group (n=68) received the usual dietary advice. The duration of intervention and follow-up was 28+/-7 months.
                After 6 months, protein intake differed only by 0.08 g/kg/day between the study groups. Subsequently, this difference decreased and eventually disappeared. An initial effect of protein restriction on albuminuria in favor of the experimental group was not sustained, and the glomerular filtration rate decreased in the experimental group at a 1.6+/-2.2 ml/min/1.73 m(2) y lower rate than in the control group (P=0.5). Comparison of patients in the experimental group with a decrease in protein intake of at least 0.20 g/kg/day, with controls with no decrease, indicated a similarly small and insignificant effect on glomerular filtration rate.
                It is concluded that, in the longer term prevention or delay of renal damage in patients with type 2 diabetes, protein restriction is neither feasible nor efficacious.
The results show that reducing protein intake appears to slightly slow progression to renal failure but not statistically significantly so. However, questions concerning the level of protein intake and compliance remain. Further longer-term research on large representative groups of patients with both type 1 and type 2 diabetes mellitus is necessary. Because of the variability amongst patients, there might perhaps be a six month therapeutic trial of protein restriction in all individuals, with continuation only in those who responded best. Trials are required of different types of protein.