[Medical management of uric acid renal stones, case description.] / Manejo médico de los cálculos renales de ácido úrico, a próposito de un caso.

Uric acid renal stones are a frequent and important part of our clinical practice. Conservative treatment through diet and urine alkalinization with citrate and teobromina seem a promising combination for treatment of those stones. We show on our cases a complete resolution of staghorn stone at 12 weeks of allopurinol and lit-control pH Up treatment, without adverse events and avoiding surgical treatment.

Los cálculos urinarios de ácido úrico corresponden a una patología frecuente e importante en nuestra práctica clínica. El tratamiento conservador mediante medidas higiénico-dietéticas y la correcta alcalinización urinaria mediante citrato y teobromina parece ser una combinación prometedora para el tratamiento y resolución de estas litiasis. Así lo pone de manifiesto uno de nuestros casos, donde se observa la resolución completa de una litiasis coraliforme de ácido úrico durante 12 semanas de tratamiento con Alopurinol y Lit-Control pH Up sin observar reacciones adversas y evitando la necesidad de medidas quirúrgicas invasivas.

Manejo médico de los cálculos renales de ácido úrico, a próposito de un caso / Medical management of uric acid kidney stones, about a case

Los cálculos urinarios de ácido úrico corresponden a una patología frecuente e importante en nuestra práctica clínica. El tratamiento conservador mediante medidas higiénico-dietéticas y la correcta alcalinización urinaria mediante citrato y teobromina parece ser una combinación prometedora para el tratamiento y resolución de estas litiasis. Así lo pone de manifiesto uno de nuestros casos, donde se observa la resolución completa de una litiasis coraliforme de ácido úrico durante 12 semanas de tratamiento con Alopurinol y Lit-Control pH Up sin observar reacciones adversas y evitando la necesidad de medidas quirúrgicas invasivas.(AU)

Uric acid renal stones are a frequent and important part of our clinical practice. Conservative treatment through diet and urine alkalinization with citrate and teobromina seem a promising combination for treatment of those stones. We show on our cases a complete resolution of staghorn stone at 12 weeks of allopurinol and lit-control pH Up treatment, without adverse events and avoiding surgical treatment.(AU)

Tubular dysfunction in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia. METHODS: Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22-32) and 745 g (range 316-999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-ß-D-glucosaminidase-to-creatinine ratio (NAG/Cr), ß2 microglobulin-to-creatinine ratio (ß2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4-6 years later. RESULTS: Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, ß2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine ß2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and ß2m/Cr remained similar or increased. CONCLUSION: Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.

Individualized treatment strategies for hyperuricemia informed by a semi-mechanistic exposure-response model of uric acid dynamics.

To provide insight into pharmacological treatment of hyperuricemia we developed a semi-mechanistic, dynamical model of uric acid (UA) disposition in human. Our model represents the hyperuricemic state in terms of production of UA (rate, PUA), its renal filtration (glomerular filtration rate, GFR) and proximal tubular reabsorption (fractional excretion coefficient, FE). Model parameters were estimated using data from 9 Phase I studies of xanthine oxidase inhibitors (XOI) allopurinol and febuxostat and a novel uricosuric, the selective UA reabsorption inhibitor lesinurad, approved for use in combination with a XOI. The model was qualified for prediction of the effect of patients' GFR and FE on concentration of UA in serum (sUA) and UA excretion in urine and their response to drug treatment, using data from 2 Phase I and 4 Phase III studies of lesinurad. Percent reduction in sUA from baseline by a XOI is predicted to be independent of GFR, FE or PUA. Uricosurics are more effective in underexcreters of UA or patients with normal GFR. Co-administration of a XOI and an uricosuric agent should be considered for patients with high sUA first in the treatment algorithm of gout before uptitration of XOI. The XOI dose in combination with a uricosuric can be reduced compared to XOI alone for the same target sUA to the degree dependent on patient's GFR and FE. This exposure-response model of UA can be used to rationally select the best drug treatment option to lower elevated sUA in gout patients under differing pathophysiological situations.

Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention.

Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus.

Plasma uric acid (PUA) is associated with metabolic, cardiovascular, and renal abnormalities in patients with type 2 diabetes but is less well understood in type 1 diabetes (T1D). Our aim was to compare PUA levels and fractional uric acid excretion (FEUA) in patients with T1D vs. healthy controls (HC) during euglycemia and hyperglycemia. PUA, FEUA, blood pressure (BP), glomerular filtration rate (GFR-inulin), and effective renal plasma flow (ERPF-paraaminohippurate) were evaluated in patients with T1D (n = 66) during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (9-11 mmol/l), and in HC (n = 41) during euglycemia. To separate the effects of hyperglycemia vs. increased glycosuria, parameters were evaluated during clamped euglycemia in a subset of T1D patients before and after sodium glucose cotransporter 2 (SGLT2) inhibition for 8 wk. PUA was lower in T1D vs. HC (228 ± 62 vs. 305 ± 75 µmol/l, P < 0.0001). In T1D, hyperglycemia further decreased PUA (228 ± 62 to 199 ± 65 µmol/l, P < 0.0001), which was accompanied by an increase in FEUA (7.3 ± 3.8 to 11.6 ± 6.7, P < 0.0001). In T1D, PUA levels correlated positively with SBP (P = 0.029) and negatively with ERPF (P = 0.031) and GFR (P = 0.028). After induction of glycosuria with SGLT2 inhibition while maintaining clamped euglycemia, PUA decreased (P < 0.0001) and FEUA increased (P < 0.0001). PUA is lower in T1D vs. HC and positively correlates with SBP and negatively with GFR and ERPF in T1D. Glycosuria rather than hyperglycemia increases uricosuria in T1D. Future studies examining the effect of uric acid-lowering therapies should account for the impact of ambient glycemia, which causes an important uricosuric effect.