I.I. Golodnikov¹, Z.Sh. Pavlova², A.A. Kamalov³, A.V. Savilov4

2,3 Medical Scientific-Educational Center of Lomonosov Moscow State University (Moscow, Russia), 

1–3 Lomonosov Moscow State University (Moscow, Russia), 

4 Central Military Clinical Hospital n.a. P.V. Mandryk of the Ministry of Defense of the Russian Federation (Moscow, Russia)

CaSR (calcium-sensing receptor) is a G coupled plasma membrane protein. The main function is a reaction to a certain level of calcium in the blood and inside the structural departments of the nephron.

CaSR is interesting in the aspect of nephrolithiasis in view of its active involvement in calcium metabolism. Moreover, it affects this metabolism from different angles. Firstly, it has a significant effect on the metabolism of vitamin D, reducing its synthesis, through the suppression of 1α-hydroxylase and at the same time increasing the number of its receptors. Secondly, with an increase in blood calcium levels, CaSR inhibits ROMK, which is a limiting factor in calcium reabsorption, thereby regulating serum calcium levels. Thirdly, CaSR controls the expression of claudin proteins of type 14, 16, 19, providing facilitated diffusion of calcium through special intercellular channels or vice versa, preventing this diffusion. 

The importance of the physiological functioning of CaSR is determined not only by its significant influence on calcium metabolism, but also by the fact that a number of diseases associated with CaSR defects have already been confirmed: autosomal dominant hypokalemia, family isolated hyperparathyroidism, and a number of genetic disorders of the CaSR associated with kidney stones have been found. In other words, the relevance of genetic analysis for CaSR and its polymorphisms or mutations in relation to nephrolithiasis is reasonable. About the KL-1 gene and the two forms of the α-klotho protein encoded by it, shortened and full-sized, it is known that they are expressed mainly in tissues associated with the regulation of calcium metabolism, which attracts our attention regarding kidney stone disease. 

The functions of α-klotho are also relevant in the aspect of the topic we are considering: the secretion of parathyroid hormone and a subsequent increase in serum calcium; rapid regulation of extracellular calcium; regulation of calcium levels, through the suppression of calcitriol synthesis, by conducting an FGF23 signal. In addition, α-klotho also serves as the coenzyme / coreceptor of FGF23, binding to the FGF23 receptor, significantly increasing the affinity of the receptor for FGF23, which in turn will not only inhibit the synthesis of vitamin D, but also increase the activity of 24-hydroxylase responsible for the synthesis and Vitamin D catabolism, respectively.

Golodnikov I.I., Pavlova Z.Sh., Kamalov A.A., Savilov A.V. Сalcium-sensing receptor, α-klotho and FGF21 in the development of nephrolithiasis. Review article. Technologies of living systems. 2021. V. 18. № 1. P. 32–40. DOI: 10.18127/j20700997202101-03 (In Russian).

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