Signification of distal urinary acidification defects in hypocitraturic patients

BACKGROUND AND OBJECTIVES: Hypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia. MATERIALS AND METHODS: This retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO(3)(-) (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO(3)(-) had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH(4)(+) ≥33 μmol/min and defined idiopathic hypocitraturia. RESULTS: Eleven patients (16.4%) had low HCO(3)(-) and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO(3)(-); of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH(4)(+) excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH(4)(+) excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24–0.47] vs. 0.22 [0.08–0.37] mmol/mmol creatinine (P = 0.04). CONCLUSIONS: Patients with hypocitraturia and normal plasma HCO(3)(-) frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH(4)(+) response to the acid load. Those patients with impaired urine acidification capacity but preserved NH(4)(+) excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention.