Genetic Risk Factors for Idiopathic Urolithiasis: The Causative Role of Genes in Stones Formation

Background: The genetic factor of urolithiasis plays an important role in the etiology. Elucidation of responsible genes can lead to better targeted gene therapy and prevention in the future. This article aims to explain various genetic factors that play a role in kidney stone formation Method: A review article on urolithiasis based on a genetic approach is reported to underlie stone formation. A total of 41 abstracts and research articles published by internationally reputed journals were selected based on the keywords genetic factors and urolithiasis. Summary: A deeper understanding of the genetic factors that play a role in the mechanisms of stone formation and advances in molecular and pharmacogenomics have revolutionized diagnosis and treatment, and paved the way for the identification of new therapeutic targets and treatment approaches based on genetic engineering.

Effect of Black Tea Consumption on Urinary Risk Factors for Kidney Stone Formation

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.

Mechanisms Underlying Calcium Nephrolithiasis

Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice. Consequently, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal tubular transport. Kidney stone formation is complex and driven by high concentrations of calcium-oxalate or calcium-phosphate in the urine. After discussing the mechanism mediating renal calcium salt precipitation, we review recent discoveries in renal tubular calcium transport from the proximal tubule, thick ascending limb, and distal convolution. Furthermore, we address how calcium is absorbed from the intestine and mobilized from bone. The effect of acidosis on bone calcium resorption and urinary calcium excretion is also considered. Although recent discoveries provide insight into these processes, much remains to be understood in order to provide improved therapies for hypercalciuria and prevent kidney stone formation. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Multicolor imaging of calcium-binding proteins in human kidney stones for elucidating the effects of proteins on crystal growth

The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. Calcium-binding proteins in kidney stones have great influences on the stone formation. The spatial distributions of these proteins in kidney stones are essential for evaluating the in vivo effects of proteins on the stone formation, although the actual distribution of these proteins is still unclear. We reveal micro-scale distributions of three different proteins, namely osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in human kidney stones retaining original mineral phases and textures: calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). OPN and RPTF-1 were distributed inside of both COM and COD crystals, whereas Cal-A was distributed outside of crystals. OPN and RPTF-1 showed homogeneous distributions in COM crystals with mosaic texture, and periodically distributions parallel to specific crystal faces in COD crystals. The unique distributions of these proteins enable us to interpret the different in vivo effects of each protein on CaOx crystal growth based on their physico-chemical properties and the complex physical environment changes of each protein. This method will further allow us to elucidate in vivo effects of different proteins on kidney stone formation.

Effect of calcium content of diet on crystal formation in urine of patients with calcium oxalate stones: a randomized crossover clinical trial

Background Patients with idiopathic calcium oxalate stones are advised to consume a low-oxalate diet to prevent recurrence. In this study, on patients with calcium oxalate stones we have attempted to determine the effect of calcium content of diet on the formation of calcium oxalate crystals in urine by in vitro supersaturation study of fresh postprandial urine samples and observing the morphology of the crystals formed using polarized optical microscopy. Methods The trial was conducted as a prospective interventional randomised crossover clinical trial in a repeated measures design. Sixty patients with calcium oxalate stones and no metabolic abnormalities in urine treated by lithotripsy at a tertiary care centre during the period May 2016 to May 2019 were recruited. Following a 14 h overnight fasting, urine samples were collected after providing the patient with either a low- or high-calcium meal for breakfast followed four hours later, by high-oxalate meal for lunch. Urine was tested for multiple parameters including urine pH, specific gravity, calcium/creatinine ratio and supersaturation of urine with sodium oxalate followed by optical density measurement by spectrophotometry and microscopic analysis of crystals formed. Results Optical density values and calcium/creatinine ratio of urine samples obtained after high-calcium meal are significantly higher than in corresponding sample obtained after low-calcium meal (p < 0.001). These findings were reflected in the morphology of formed crystals in their size, shape and number. When urinary calcium levels were low, no crystals were formed during supersaturation study of postprandial urine samples following a high-oxalate diet. Conclusions High calcium content in diet significantly contributes to kidney stone formation. There is a lower risk of kidney stone formation with a low-calcium meal even on consumption of a high-oxalate diet.