Long-term combined treatment with thiazide and potassium citrate in nephrolithiasis does not lead to hypokalemia or hypochloremic metabolic alkalosis

Long-term combined treatment with thiazide and potassium citrate in nephrolithiasis does not lead to hypokalemia or hypochloremic metabolic alkalosis.BackgroundPotassium citrate is commonly used in combination with a thiazide diuretic in the medical management of recurrent hypercalciuric nephrolithiasis. However, concerns have been raised that administration of this nonchloride potassium alkali with a kaliuretic and natriuretic agent such as thiazide may not be efficacious in correcting or preventing hypokalemia, and may produce hypochloremic metabolic alkalosis. This retrospective analysis was conducted to determine if these two potential complications are encountered in patients on long-term potassium citrate and thiazide therapy.MethodsData were collected on 95 patients who had been on combination therapy for at least 4 months from the stone clinics of the University of Texas Southwestern Medical Center, Duke University Medical Center, and Ochsner Clinic.ResultsMean serum potassium concentration remained within normal limits without a significant decrease during combined therapy. Serum chloride was significantly lower from pretreatment but by only 1 mEq/L and remained within normal limits throughout treatment. There was a small increase in serum bicarbonate concentration compared to the baseline level of less than 1 mEq/L at 8 to 12 and 18 to 24 months, but not at other treatment periods.ConclusionCo-administration of potassium citrate did not induce hypokalemia or hypochloremic metabolic alkalosis in our thiazide-treated patient population

Relative effect of urinary calcium and oxalate on saturation of calcium oxalate Rapid Communication

Relative effect of urinary calcium and oxalate on saturation of calcium oxalate.BackgroundThe study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate.MethodsA retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A “theoretical” curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents.ResultsAt the stability constant of 7.07 × 103, the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 × 103 from the Equil 2 that is considered the “gold standard,” calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r = 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r = 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate).ConclusionAmong calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate

Natural urinary macromolecular inhibitors: Attenuation of inhibitory activity by urate salts

Natural urinary macromolecular inhibitors: Attenuation of inhibitory activity by urate salts. The interaction between naturally occurring urinary macromolecular inhibitors of calcium oxalate nucleation and crystal growth and the various urate salts was explored in vitro. The fraction of macromolecules chosen for the study was the one which was previously shown to have a potent inhibitor activity against calcium oxalate nucleation and one which gave a satisfactory yield. As little as 0.025 mg/ml of this fraction (Y-b) was found to inhibit calcium oxalate nucleation by nearly 50% and crystal growth by 31%. Prior incubation of the solution containing Y-b with increasing crystal surface areas (1.1 to 26.2mm2/ml) of monosodium urate (NaU), monopotassium urate (KU), or uric acid (UA) attenuated the inhibitory action of the Y-b fraction for both nucleation and crystal growth of calcium oxalate. The most prominent effect was elicited by NaU at surface areas as small as 1.1mm2/ml. Potassium urate and UA were without significant effects until surface areas of 13.1 and 2.6mm2/ml, respectively, were achieved. These results support an important pathogenetic role for urates (particularly NaU) in the development of hyperuricosuric calcium urolithiasis.L'inhibiteurs des macromolécules urinaires normalement: Atténuation de la activité inhibiteur par les sels d'urate. L'interaction entre les inhibiteurs macromoléculaires normalement présents dans l'urine de la nucléation de l'oxalate de calcium et de la croissance cristalline et les divers sels d'urate a été explorée in vitro. La fraction de macromolécules choisies pour l'étude étaient celle dont il avait été montré auparavant qu'elle était porteuse d'une activité inhibitrice puissante contre la nucléation d'oxalate de calcium et celle qui donnait un rendement satisfaisant. Une quantité aussi faible que 0,025 mg/ml de cette fraction (Y-b) s'est avérée capable d'inhiber la nucléation d'oxalate de calcium d'environ 50% et la croissance cristalline de 31%. Une incubation préalable d'une solution contenant Y-b avec des surfaces de cristaux croissantes (1,1 à 26,2mm2/ml) d'urate monosodique (NaU), d'urate monopotassique (KU), ou d'acide urique (UA) a atténué l'action inhibitrice de la fraction Y-b sur la nucléation et la croissance cristalline de l'oxalate de calcium. L'effet le plus marqué était obtenu par du NaU sur des surfaces aussi faibles que 1.1mm2/ml. L'urate de potassium et l'UA étaient sans effet significatif jusqu'à des surfaces de 13,1 et 2,6mm2/ml, respectivement. Ces résultats sont en faveur d'un rôle physiopathologique important des urates (particulièrement de NaU) dans le développement de la lithiase urinaire calcique hyperuricosurique

Pathogenesis of primary hypercalciuria

Hypercalciuria may be classified into absorptive, renal and re- sorptive forms, depending on whether the primary defect is in- testinal hyperabsorption of calcium, renal leak of calcium, or excessive bone resorption. In absorptive hypercalciuria, the pathogenetic role of vitamin D is uncertain, and mutations in the chloride channel may occur mainly in association with Dent’s disease. Early studies suggest that a new soluble adenylyl cyclase ( A H R A C ) may be etiologically important in this condition, since base changes in this gene occur much more frequently and are directly correlated with intestinal cal-cium absorption. The distal nephron is the site of reabsorption of the final 20% of filtered calcium. The transcellular reabsorption of calcium begins with a passive entry of Ca 2 + through apical calcium channels, followed by diffusion through cytosol and active ex- trusion across the basolateral membrane. Calcium transport in the nephron is regulated by luminal pH, calcitriol, estrogen, parathyroid hormone, rostaglandin E 2 , and sodium load. A biochemical picture of renal hypercalciuria may be produced by acid load from dietary animal proteins, prostaglandin E 2 ex- cess, sodium load, hypoparathyroidism, and estrogen defi- ciency. So far, mutations in apical calcium channel have not been found. The hallmark of resorptive hypercalciuria is primary hyper-parathyroidism. Bone loss often accompanies bsorptive hy- percalciuria. A H R A C may be implicated, since base changes in this gene are inversely correlated with spinal bone density. Dietary acid load from high nimal protein diet may cause hy- percalciuria, in part by stimulating bone loss