Recent studies have suggested that defective medullary trapping of ammonia underlies the acidosis associated with renal failure and sets in motion maladaptive compensatory mechanisms that contribute to the progression of renal disease. Since a renal concentrating defect is an early functional abnormality in autosomal dominant polycystic kidney disease (ADPKD), defective medullary trapping and urinary excretion of ammonia may also occur early and have important pathophysiological consequences. The urinary pH and excretions of ammonia, titratable acid, and bicarbonate, were measured during a 24-hour baseline period and following the administration of ammonium chloride (100 mg/kg body wt) in ADPKD patients with normal glomerular filtration rate and in age- and gender-matched healthy control subjects. The distal nephron hydrogen ion secretory capacity was assessed during a bicarbonate infusion. Ammonia, sodium, pH, C3dg, and C5b-9 were measured in cyst fluid samples. The excretion rates of ammonia during the 24-hour baseline period and following the administration of ammonium chloride were significantly lower, and the relationship of ammonia excretion to urinary pH was significantly shifted downward in ADPKD. No difference in the increment of urinary pCO2 (Δ pCO2) or the peripheral blood-urine pCO2 gradient (U- B pCO2) between ADPKD patients and control subjects was detected during a sodium bicarbonate infusion. Calculated concentrations of free-base ammonia in cyst fluid samples exceeded those calculated from reported concentrations of ammonia in renal venous blood of normal subjects. C3dg and C5b-9 were detected in some cyst fluids. The urinary excretion of ammonia is reduced in ADPKD patients with normal glomerular filtration rate. This reduction is not explained by a lower production of ammonia in the renal cortex or by a defect of proton secretion in the collecting ducts. It is likely due to an impaired renal concentrating mechanism and reduced trapping of ammonia in the renal medulla. It may contribute to the pathogenesis of nephrolithiasis and, more importantly, to the progression of the interstitial inflammation and cystic changes seen in ADPKD.
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