Phosphate depletion arrests progression of chronic renal failure independent of protein intake

摘要

Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 0.1 vs. 1.62 0.6 mg/deciliter, 17.0 10.3 vs. 257.6 13.4 mg/24 hr, and 16.6 4.4 vs. 39.2 11.7 ml/24 hr, respectively, all P 2+) were normal, the rats were separated into two groups, matched and paired by body weight and SCr, and housed separately in metabolic cages. Animals of one group ingested a normal diet supplemented with dihydroxyaluminum aminoacetate (DHAAA), 15 g%, to induce phosphate depletion (PD). The second group ingested the same diet supplemented with 7.5% glycine and was the phosphate replete (PR) group. All rats were pair fed throughout the study to maintain similar caloric, protein, carbohydrate, vitamin, and mineral intakes. At six weeks after separation, SPi was decreased in PD vs. PR group (2.85 0.8 vs. 6.71 1.2 mg/deciliter, P 2+ was increased in the PD group (11,98 0.7 vs. 10.03 0.7 mg/deciliter, P < 0.001). Urine urea nitrogen, body weight, and sodium, potassium and solute excretion were similar between the groups. At six weeks, urine protein, serum cholesterol, and urine volume were decreased in PD compared to PR animals (75.4 41.8 vs. 296.0 70.5 mg/24 hr, P < 0.001; 105.5 30.4 vs. 147.6 34.6 mg/deciliter, P < 0.05; and 35.0 5.7 vs. 45.2 7.5 ml/24 hr, P < 0.05, respectively). Evidence of significantly greater progressive renal injury, as assessed by SCr, in the PR group occurred by the 12th week, and by the 14th week SCr had risen to 2.96 0.8 vs. 1.58 0.3 mg/deciliter, P < 0.01 and creatinine clearance had decreased (46.5 47.3 vs. 282.9 66.8 l/min, P < 0.005). Tissue calcium content of heart, aorta and kidney was higher in the PR group. At 14 weeeks, histologic examination of renal tissue from PR rats demonstrated more severe glomerular sclerosis, interstitial inflammation with fibrosis, and tubular atrophy and dilation compared to the PD group. PD alone, therefore, exerts a beneficial effect to prevent the progression of chronic renal failure in the remnant kidney model of the rat.