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Genetic basis of renal cellular dysfunction and the formation of kidney stones

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Abstract

Nephrolithiasis is a result of formation and retention of crystals within the kidneys. The driving force behind crystal formation is urinary supersaturation with respect to the stone-forming salts, which means that crystals form when the concentrations of participating ions are higher than the thermodynamic solubility for that salt. Levels of supersaturation are kept low and under control by proper functioning of a variety of cells including those that line the renal tubules. It is our hypothesis that crystal deposition, i.e., formation and retention in the kidneys, is a result of impaired cellular function, which may be intrinsic and inherent or triggered by external stimuli and challenges. Cellular impairment or dysfunction affects the supersaturation, by influencing the excretion of participating ions such as calcium, oxalate and citrate and causing hypercalciuria, hyperoxaluria or hypocitraturia. The production and excretion of macromolecular promoters and inhibitors of crystallization is also dependent upon proper functioning of the renal epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin, Tamm-Horsfall protein, bikunin, etc. are most likely produced by the impaired cells.

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Acknowledgments

Research supported by NIH grants # RO1DK065658 and RO1DK59765, and The University of Florida Center for the Study of Lithiasis and Pathological Calcification.

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  1. Department of Pathology and Center for the Study of Lithiasis and Pathological Calcification, University of Florida, Gainesville, FL, USA

    Saeed R. Khan

  2. Department of Urology, College of Medicine, University of Florida, Gainesville, FL, USA

    Benjamin K. Canales

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Correspondence to Saeed R. Khan.

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Khan, S.R., Canales, B.K. Genetic basis of renal cellular dysfunction and the formation of kidney stones. Urol Res 37, 169–180 (2009). https://doi.org/10.1007/s00240-009-0201-9

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