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It is known that symptoms of uremia in patients who have end-stage renal disease (ESRD) can be reduced and the need for renal replacement therapy postponed by restricting protein intake. Studies in animals with insufficient renal tissue have also demonstrated that high protein intake can accelerate and low protein intake can diminish the rate of decline in renal function. However, such findings have never been substantiated in humans with CRI, and especially in children, where significant limitation in protein intake could interfere with growth.
The current European multicenter study sought to provide a diet with adequate energy content and moderate protein restriction and prospectively follow its possible effect on the rate of progression of chronic renal insufficiency in children ages 2-18 years. One hundred ninety-one children were followed for two years, and, of these, 112 continued for an optional third year. Before randomizing them into control and study groups, the children were stratified according to their underlying renal disorder (e.g., glomerulonephritis, obstruction uropathy, dysplasia) and whether they exhibited progressive disease for the six months preceding the study. Creatinine clearances at entry were between 15 and 60 mL/min/1.73m2. Protein intake for the study group was regulated to be 0.81.1 g/kg ideal body weight/day and was significantly lower than the control group. There were no significant differences between the groups with regard to fall in GFR or need for renal replacement therapy either at two or three years. Growth, as reflected by height, weight, and upper arm circumference, was not different in either group. Multivariate regression analysis of the population showed that positive predictors of decline in renal function were heavy proteinuria (> 50 mg/kg/d) and elevated systolic blood pressure (> 120 mmHg).
The inexorable progression of renal disease in some children is a frustrating fact of life that nephrologists would like to be able to influence. Although pharmacologic therapy has efficacy in some conditions (e.g., alternate day steroids in membranoproliferative glomerulonephritis), the relentless decline in renal functioning leaves us to supportively treat the accompanying complications including anemia, growth failure, acidosis, osteodystrophy, and hypertension. The prospect, therefore, of effectively intervening with a relatively simple dietary therapy that might delay the time at which dialysis or transplantation is necessary is as appealing as it is intriguing. Unfortunately, the current study does not find protein restriction effective, at least after 2-3 years. It is worth noting that the protein restriction was not severe and that the study group consumed 125% of the WHO recommended intake by diary report and an even higher 141% by urinary urea-nitrogen measurement. Although we might conclude that more severe protein restriction might yield more significant differences between the two groups, it is just as reasonable to conclude that more severe and sustained protein restriction is simply not feasible in children. It appears we shall need to look elsewhere for favorably altering the progression of chronic renal insufficiency, perhaps through more effective and aggressive control of hypertension.