Estrogen's Tissue-Specific Regulation of the SLC26A6 Anion Transporter Reveal a Phenotype of Kidney Stone Disease in Estrogen-Deficient Females: A Systematic Review.

Kidney stone formation is an intricate process that involves a disruption in the interplay of the multiple organs and systems involved in regulating the concentration of specific ions in the body. Women who have gone through menopause are susceptible to kidney stone disease. This systematic review aims to investigate the potential influence of estrogen on kidney function and oxalate homeostasis, notably through the anion transporter SLC26A6 (also known as putative anion transporter 1 or PAT1) in females. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, a systematic search of online databases included Pubmed, ScienceDirect Journals, and Ingenta Connect Journals. Predetermined criteria to include and exclude papers, gathering articles published between 2012 and 2022, were determined. After a thorough analysis, eight articles (three cohorts, one case-control, one in vivo, one in vitro, and two cross-sectional studies) were identified for the final quality assessment review.  The eight selected and quality-assessed articles provided evidence of a directly proportional connection between estrogen and kidney function. A correlation between serum estrogen levels and the development of kidney stone disease was confirmed. Administration of β-estradiol was shown to effectively inhibit the function of the anion transporter PAT1 in a tissue-specific manner. In the case of the kidney, estrogen was observed to down-regulate PAT1, which led to a reduction in oxalate transporting activity and, consequently, a decrease in kidney stone formation. Consensus suggests that serum estrogen levels and optimal kidney functioning are interrelated. Furthermore, analysis of the quality-assessed articles and a comprehensive literature review revealed estrogen's tissue-specific regulation of the PAT1 anion transporter aids in maintaining kidney function and anion homeostasis. Additional research is needed to solidify estrogen's role in kidney stone disease to determine its therapeutic value in clinical practice.