Hyperuricosuric calcium urolithiasis.

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.

Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation.

PURPOSE: The prevalence of kidney stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of stone formation and stone types are scarce. We investigated temporal changes in stone composition, and demographic, serum and urinary parameters of kidney stone formers from 1980 to 2015. MATERIALS AND METHODS: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or uric acid stones at an initial visit to a university kidney stone clinic from 1980 to 2015. RESULTS: From 1980 to 2015, the proportion of uric acid stones in all stone formers increased from 7% to 14%. While age and body mass index increased with time in both uric acid and calcium stone formers, uric acid stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium stone formers. The proportion of females with stones has increased over time but the increase in female gender was more prominent among calcium stone formers. Urinary pH, phosphorus, oxalate and sodium increased with time in 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 stones was urinary pH. Limitations of this study include the retrospective single center design and the 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 stone formers but not uric acid stone formers. Urinary pH is the most prominent factor distinguishing uric acid from calcium stones.

Effect of acute hyperinsulinemia on magnesium homeostasis in humans.

BACKGROUND: Insulin may influence magnesium homeostasis through multiple mechanisms. Acutely, it stimulates the shift of magnesium from plasma into red blood cells and platelets, and in vitro, it stimulates the activity of the TRPM6 channel, a key regulator of renal magnesium reabsorption. We investigated the impact of hyperinsulinemia on magnesium handling in participants with a wide range of insulin sensitivity. METHOD: Forty-seven participants were recruited, including 34 nondiabetic controls and 13 with type 2 diabetes mellitus. After stabilization under fixed metabolic diet, participants underwent hyperinsulinemic-euglycemic clamp. Serum and urine samples were collected before and during hyperinsulinemia. Change in serum magnesium, urinary magnesium to creatinine (Mg2+ :Cr) ratio, fractional excretion of urinary magnesium (FEMg2+ ), and estimated transcellular shift of magnesium were compared before and during hyperinsulinemia. RESULTS: Hyperinsulinemia led to a small but statistically significant decrease in serum magnesium, and to a shift of magnesium into the intracellular compartment. Hyperinsulinemia did not significantly alter urinary magnesium to creatinine ratio or fractional excretion of urinary magnesium in the overall population, although a small but statistically significant decline in these parameters occurred in participants with diabetes. There was no significant correlation between change in fractional excretion of urinary magnesium and body mass index or insulin sensitivity measured as glucose disposal rate. CONCLUSIONS: In human participants, acute hyperinsulinemia stimulates the shift of magnesium into cells with minimal alteration in renal magnesium reabsorption, except in diabetic patients who experienced a small decline in fractional excretion of urinary magnesium. The magnitude of magnesium shift into the intracellular compartment in response to insulin does not correlate with that of insulin-stimulated glucose entry into cells.

Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis.

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 (Ca(2+)) 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 Ca(2+) 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.

Drug-Induced Metabolic Acidosis.

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.