RENAL AMMONIA IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

Recent studies have suggested that defective medullary trapping of amm onia underlies the acidosis associated with renal failure and sets in motion maladaptive compensatory mechanisms that contribute to the prog ression of renal disease. Since a renal concentrating defect is an ear ly functional abnormality in autosomal dominant polycystic kidney dise ase (ADPKD), defective medullary trapping and urinary excretion of amm onia may also occur early and have important pathophysiological conseq uences. The urinary pH and excretions of ammonia, titratable acid, and bicarbonate, were measured during a 24-hour baseline period and follo wing the administration of ammonium chloride (100 mg/kg body wt) in AD PKD patients with normal glomerular filtration rate and in age- and ge nder-matched healthy control subjects. The distal nephron hydrogen ion secretory capacity was assessed during a bicarbonate infusion. Ammoni a, sodium, pH, C3dg, and C5b-9 were measured in cyst fluid samples. Th e excretion rates of ammonia during the 24-hour baseline period and fo llowing the administration of ammonium chloride were significantly low er, and the relationship of ammonia excretion to urinary pH was signif icantly shifted downward in ADPKD. No difference in the increment of u rinary pCO(2) (Delta pCO(2)) or the peripheral blood-urine pCO(2) grad ient (U-B pCO(2)) between ADPKD patients and control subjects was dete cted during a sodium bicarbonate infusion. Calculated concentrations o f free-base ammonia in cyst fluid samples exceeded those calculated fr om reported concentrations of ammonia in renal venous blood of normal subjects. C3dg and C5b-9 were detected in some cyst fluids. The urinar y excretion of ammonia is reduced in ADPKD patients with normal glomer ular filtration rate. This reduction is not explained by a lower produ ction of ammonia in the renal cortex or by a defect of proton secretio n in the collecting ducts. It is likely due to an impaired renal conce ntrating mechanism and reduced trapping of ammonia in the renal medull a. It may contribute to the pathogenesis of nephrolithiasis and, more importantly, to the progression of the interstitial inflammation and c ystic changes seen in ADPKD.