Successful Diabetic Control as Measured by Hemoglobin A1c Is Associated with Lower Urine Risk Factors for Uric Acid Calculi.

INTRODUCTION AND OBJECTIVES: To examine the association of glycemic control, including strict glycemic control, with 24-hour urine risk factors for uric acid and calcium calculi. MATERIALS AND METHODS: With institutional review board (IRB) approval, we identified 183 stone formers (SFs) with 459 twenty-four-hour urine collections. Hemoglobin A1c (HgbA1c) measures were obtained within 3 months of the urine collection. Collections were categorized into normoglycemic (NG, HgbA1c < 6.5) and hyperglycemic (HG, HgbA1c ≥ 6.5) cohorts; 24-hour urine parameters were compared. The NG cohort was further divided into patients with and without a history of diabetes mellitus (DM) type 2. Variables were analyzed using chi-square, Welch's t-test and multivariate linear regression to adjust for clustering, body mass index (BMI), age, gender, thiazide use, and potassium citrate use. RESULTS: Patients in the HG group were older with higher BMI. Multivariate analysis of the total study population revealed that hyperglycemia correlated with lower pH, higher uric acid relative saturation (RS), lower brushite RS, and higher citrate. NG SFs with and without a history of DM had similar risk factors for uric acid stone formation. Among NG SFs, those with DM had higher urine calcium and calcium oxalate RS than those without DM. However, this difference may be related to other factors since neither parameter correlated with DM on multivariate regression (p > 0.05). CONCLUSIONS: Successful glycemic control may be associated with reduced urinary risk factors for uric acid stone formation. Patients with well-controlled DM had equivalent risk factors to those without DM. Glycemic control should be considered a target of the multidisciplinary medical management of stone disease.

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 HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 µmol/min and defined idiopathic hypocitraturia. RESULTS: Eleven patients (16.4%) had low HCO3- 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 HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ 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 HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention.