Chronic metabolic acidosis in azotemic rats on a high-phosphate diet haltsthe progression of renal disease

Background. Hyperphosphatemia and metabolic acidosis are general features o f advanced chronic renal failure (RF), and each may affect mineral metaboli sm. The goal of the present study was to evaluate the effect of chronic met abolic acidosis on the development of hyperparathyroidism and bone disease in normal and azotemic rats on a high-phosphate diet. Our assumption that t he two groups of azotemic rats (acid-loaded vs. non-acid-loaded) would have the same degree of renal failure at the end of the study proved to be inco rrect. Methods. Four groups of rats receiving a high-phosphate (1.2%), normal-calc ium (0.6%) diet for 30 days were studied: (I) normal (N); (2) normal + acid (N + Ac) in which 1.5% ammonium chloride (NH4Cl) was added to the drinking water to induce acidosis; (3) RF, 5/6 nephrectomized rats; and (4) RF + ac id (RF + Ac) in which 0.75% NH4Cl was added to the drinking water of 5/6 ne phrectomized rats to induce acidosis. Results. At sacrifice, the arterial pH and serum bicarbonate were lowest in the RF + Ac group and were intermediate in the N + Ac group. Serum creatin ine (0.76 +/- 0.08 vs. 1.15 +/- 0.08 mg/dL), blood urea nitrogen (52 +/- 8 vs. 86 +/- 13 mg/dL), parathyroid hormone (PTH; 180 +/- 50 vs. 484 +/- 51 p g/mL), and serum phosphate (7.46 +/- 0.60 vs. 12.87 +/- 1.4 mg/dL) values w ere less (P < 0.05), and serum calcium (9.00 +/- 0.28 vs. 7.75 +/- 0.25 mg/ dL) values were greater (P < 0.05) in the RF + Ac group than in the RF grou p. The fractional excretion of phosphate (FEp) was greater (P < 0.05) in th e two azotemic groups than in the two nonazotemic groups. In the azotemic g roups, the FEp was similar even though PTH and serum phosphate values were less in the RF + Ac than in the RF group. NH4Cl-induced acidosis produced h ypercalciuria in the N + Ac and RF + Ac groups. When acid-loaded (N + Ac an d RF + Ac) and non-acid-loaded (N and RF) rats were combined as separate gr oups, serum phosphate and PTH values were less for a similarly elevated ser um creatinine value in acid-loaded than in non-acid-loaded rats. Finally, t he osteoblast surface was less in the N + Ac group than in the other groups . However, in the acid-loaded azotemic group (RF + Ac), the osteoblast surf ace was not reduced. Conclusions. The presence of chronic metabolic acidosis in 5/6 nephrectomiz ed rats on a high-phosphate diet (I) protected against the progression of R F, (2) enhanced the renal clearance of phosphate, (3) resulted in a lesser degree of hyperparathyroidism, and (4) did not reduce the osteoblast surfac e. The combination of metabolic acidosis and phosphate loading may protect against the progression of RF and possibly bone disease because the harmful effects of acidosis and phosphate loading may be counterbalanced.