Update on the genetics of nephrolithiasis

Abstract

Genetic studies of calcium kidney stones evidenced the possible involvement of calcium-sensing receptor gene, vitamin D receptor gene and bicarbonate-sensitive adenylate cyclase gene, but it is uncertain which specific polymorphisms could be responsible. Thus, further studies are required to better assess the involvement of these or other genes and the interactions between different genes and between genes and environment. In addition to research in humans, the study of different strains of knock-out mice let us include the gene of phosphate reabsorption carrier NPT2, caveolin-1, protein NHERF-1, osteopontin and Tamm-Horsfall protein among the possible determinants. Further steps in the knowledge of calcium stone causes may be done using the instruments that the modern biotechnology and bioinformatics have made available to the researchers.

Figure 1

- In proximal tubular cells, the complex VDR/Vitamin D activates the transcription of phosphoenol-pyruvatecarboxyl-kinase (FEPK) gene and the function of citrate reabsorption carrier. Thus, vitamin D may decrease urinary citrate excretion. In intestinal cells, the complex VDR/Vitamin D causes a rapid non-genomic and a genomic activation of calcium absorption that occurs through apical calcium channels (TRPV6), and basolateral calcium pump. Calbindin (CBP) binds calcium ions in cytoplasm and carries them from the apical to the basolateral membrane.