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    Effect of dietary modification on urinary stone risk factors
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    The metabolic syndrome (MS) is associated with increased prevalence of kidney stones, yet the specific stone type remains largely unknown. This study was conducted to assess whether risk factors associated with calcium nephrolithiasis increase with individual characteristics of the MS. A retrospective analysis was performed in 109 non-stone-forming subjects and 128 recurrent calcium stone formers from Dallas, Texas. A separate analysis was performed in 140 recurrent calcium stone formers from Bern, Switzerland. Demographic, anthropometric, serum and urinary profiles were measured. In non-stone formers from Dallas, urinary calcium (3.6 ± 1.8 to 6.0 ± 2.9 mmol/day, P = 0.0003 for trend, zero to four features) increased with increasing features of the MS. This change was attendant with a significant rise in supersaturation index (SI) of calcium oxalate (CaOx) (2.76 ± 1.21 to 4.45 ± 1.65, P < 0.0001; zero to four features). In calcium stone formers from Dallas, urinary calcium marginally increased (5.2 ± 2.3 to 7.0 ± 4.0 mmol/day, P = 0.09; zero to four features), while urinary oxalate (356 ± 141 to 504 ± 203 μmol/day, P = 0.001; zero to four features) and SI CaOx (4.46 ± 1.80 to 6.16 ± 3.71, P = 0.009; zero to four features) significantly increased with features of the MS. However, when adjusted for confounding variables such as total volume, age, gender, urine sodium and urine sulfate, urinary calcium and SI CaOx showed no significant changes in stone formers yet remained significant in non-stone formers. In a separate cohort from Bern, Switzerland urinary calcium (6.9 ± 3.6 versus 7.0 ± 3.2, P = 0.8) and SI CaOx (3.37 ± 1.98 versus 4.04 ± 2.78, P = 0.5) did not differ between subjects with and without the MS. In non-stone formers, the risk of CaOx stone formation increases with the number of features of the MS. However, in stone-forming subjects, the propensity for CaOx precipitation is much higher but is not independently associated with increasing features of the MS.
    Urinary calcium
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    The frequency of kidney stones has increased in recent years in children and adolescents. The greatest incidence rise is seen in teenage girls and childhood stones are now more common in females than in males. Calcium-based stones are most common while infection-related stones account for less than 5% in recent studies. All children with kidney stones should undergo a thorough urinary metabolic risk factor evaluation as hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricosuria, extremes of urinary pH, and low fluid intake are seen in up to 95% of first-time pediatric stone formers. A number of effective preventive therapeutic strategies, including dietary modifications and pharmacotherapy, can be implemented in an effort to reduce the risk of stone recurrence. To optimize outcomes, pediatric stone formers should preferably be followed in stone prevention clinics by a medical team with special interest in childhood kidney stone disease.
    Hyperuricosuria
    Kidney stone disease
    Fluid intake
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    The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption-as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements.
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    Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.
    Nephrocalcinosis
    Chloride channel