Chronic metabolic acidosis in azotemic rats on a high-phosphate diet halts the progression of renal disease.
BACKGROUND
Hyperphosphatemia and metabolic acidosis are general features of advanced chronic renal failure (RF), and each may affect mineral metabolism. The goal of the present study was to evaluate the effect of chronic metabolic acidosis on the development of hyperparathyroidism and bone disease in normal and azotemic rats on a high-phosphate diet. Our assumption that the 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 incorrect.


METHODS
Four groups of rats receiving a high-phosphate (1.2%), normal-calcium (0.6%) diet for 30 days were studied: (1) 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 + acid (RF + Ac) in which 0.75% NH4Cl was added to the drinking water of 5/6 nephrectomized 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 creatinine (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 pg/mL), and serum phosphate (7.46 +/- 0.60 vs. 12.87 +/- 1.4 mg/dL) values were less (P < 0.05), and serum calcium (9.00 +/- 0.28 vs. 7.75 +/- 0.28 mg/dL) values were greater (P < 0.05) in the RF + Ac group than in the RF group. The fractional excretion of phosphate (FEP) was greater (P < 0.05) in the two azotemic groups than in the two nonazotemic groups. In the azotemic groups, 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 hypercalciuria in the N + Ac and RF + Ac groups. When acid-loaded (N + Ac and RF + Ac) and non-acid-loaded (N and RF) rats were combined as separate groups, serum phosphate and PTH values were less for a similarly elevated serum creatinine value in acid-loaded than in non-acid-loaded rats. Finally, the 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 surface was not reduced.


CONCLUSIONS
The presence of chronic metabolic acidosis in 5/6 nephrectomized rats on a high-phosphate diet (1) protected against the progression of RF, (2) enhanced the renal clearance of phosphate, (3) resulted in a lesser degree of hyperparathyroidism, and (4) did not reduce the osteoblast surface. 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.
Jara
A
A
Department of Medicine, West Los Angeles VA Medical Center and UCLA, Los Angeles, California, USA.
Felsenfeld
A J
AJ
Bover
J
J
Kleeman
C R
CR
D000138:Acidosis / Q000178:diet therapy*; D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight; D001847:Bone Diseases / Q000178:diet therapy / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood / Q000652:urine; D004032:Diet; D018450:Disease Progression; D006962:Hyperparathyroidism, Secondary / Q000178:diet therapy / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000378:metabolism; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D016226:Phosphorus, Dietary / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000178:diet therapy* / Q000378:metabolism
D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D003404:Creatinine; D002118:Calcium