Calcium-sensing receptor gene polymorphisms in patients with calcium urolithiasis: a systematic review

Figures & data

Figure 1. Intrarenal localization and roles of the CaSR. Notes: Cellular polarity of the CaSR is apical [in the proximal tubule and outer/inner medullary collecting duct (OMCD/IMCD)] and basolateral [in the thick ascending limb (TAL) and, occasionally, in the cortical collecting duct (CCD)]. Species differences exist in the distal convoluted tubule (DCT)/connecting segment (CNT), where receptor expression can be detected apically and/or basolaterally/intracellularly. PCT/PST, proximal convoluted/straight tubule; tDL/tAL, thin discending/ascending limb; MTAL/CTAL, medullary/cortical thick ascending limb; JGA, juxtaglomerular apparatus; TRPV5, transient receptor potential vanilloid 5; PMCA, plasma membrane Ca2_-ATPase; VitD, vitamin D; VDR, vitamin D receptor; NKCC2, Na_-K_-2Cl_ cotransporter 2; ROMK, renal outer medullary potassium K_ channel; PTH, parathyroid hormone; AQP2, aquaporin 2.

Figure 2. CaSR activities in a cell model from the thick ascending limb (TAL). Notes: CaSR decreases paracellular calcium reabsorption by inhibition of renal outer medullary potassium channel (ROMK)-mediated potassium recycling to the lumen that supports the luminal positive electric gradient. This gradient is the driving force for the passive paracellular calcium reabsorption in the TAL. AA, arachidonic acid; 20-HETE, 20-hydroxyeicosatetraenoic acid; PKA, protein kinase A; PLA2, phospholipase A2.

Figure 3. CaSR in distal convoluted tubule. CaSR reduces calcium pump activity (PMCA) and calcium active reabsorption.

Table 1. The associated studies regarding calcium sensing receptor gene polymorphisms in patients with nephrolithiasis.

SNP	Location	Ethnicity	Patients	Noun	Analysis
Arg990Gly	Exon 7	Italian Italian Canadian Iranian European	PHPT PHPT SF and CNTs SF and CNTs General population	94 237 899 99 20,611	AS AS HWDA AS GWAS
Ala986Ser	Exon 7	Iranian	SF and CNTs	99	AS
rs17251221	Intron 4	Taiwanese	SF and CNTs	480	AS
rs7652589	5′UTR	Italian Italian	SF and CNTs PHPT	676 332	AS AS
rs1501899	Intron 1	Italian Italian	SF and CNTs PHPT	676 332	AS AS

Notes: 5′UTR, 5′untranslated region; AS, association study; CNTs, controls; GWAS, genome-wide association study; HWDA, Hardy Weinberg disequilibrium analysis; PHPT, primary hyperparathyroidism; SF, stone formers; SNP, single-nucleotide polymorphism.