Background and objectives Idiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood. Design, setting, participants, & measurements We compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index. Results Subjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P,0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P,0.001), with the excess H + carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis. Conclusions Higher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

Purpose The prevalence of kidney stones has increased globally in recent decades. However, studies investigating the association between temporal changes in risk of stone formation and stone types are scarce. We investigated temporal changes in stone composition, demographic, serum and urinary parameters of kidney stone formers from 1980–2015. Materials and Methods Retrospective analysis of 1516 patients diagnosed with either calcium or uric acid stones at initial visits in a university kidney stone clinic from 1980–2015. Results From 1980–2015, the proportion of uric acid stones within all stone formers increased from 7% to 14%. While age and BMI of both uric acid and calcium stone formers increased over time, uric acid stone formers were consistently older, had higher BMI, and lower urinary pH than calcium stone formers. While the proportion of females with stones has increased over time, the increase in female gender was more prominent among calcium stone formers. Urinary pH, phosphorus, oxalate, and sodium increased over time within calcium stone formers, but remained unchanged in uric acid stone formers. After accounting for various parameters of stone risk, the strongest clinical discriminant of uric acid vs. calcium stone was urinary pH. Limitations of this study include the retrospective single center design and available number of patients with stone analysis. Conclusions From 1980 to 2015, the proportion of uric acid stones increased significantly. With time, there were proportionately more female calcium but not uric acid stone formers. Urinary pH is the most prominent factor distinguishing uric acid from calcium stones.

Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca2+) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca2+ or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided.

Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics.

Hyperuricosuric calcium urolithiasis is a condition of mixed calcium oxalate stones characterized by hyperuricosuria either in isolation or in conjunction with other risk factors for calcium oxalate stones such as hypercalciuria, hyperoxaluria, and hypocitraturia. There are three proposed physicochemical models of pathogenesis where urate in its crystalline phase via heterogeneous nucleation, in its colloidal phase via removal of crystallization inhibitors, and in solution via precipitation crystallization, can all increase propensity to calcium oxalate precipitation. Regardless of the model, the phenomenologic observation of urate increasing calcium oxalate precipitation appears solid. Another supporting factor are retrospective data analysis and prospective trials showing uric acid lowering reduces stones events in hyperuricosuric calcium stone formers. Due to the heterogeneity of pathogenesis of calcium oxalate stones in the unselected stone-formers, association cannot be demonstrated between uric acid excretion rate and risk of kidney stone the general population. In calcium oxalate stoners with isolated hyperuricosuria or hyperuricosuria in combination with other calcium stone risks where treatment of these traditional risks fails to reduce stone formation, urate acid lowering should be cautiously attempted. More refinement of pathogenic models and prospective controlled trials in phenotypically defined subgroups of subjects with calcium oxalate urolithiasis will be informative.