To investigate the association and potential causal effect of kidney function decline on kidney stone disease (KSD).
We evaluated linear and non-linear associations between kidney function decline-assessed by estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD)-and KSD using individual-level data from the UK Biobank and summary genome-wide association study (GWAS) data. Analyses included prospective cohort models, one-sample Mendelian randomization (MR), two-sample MR, genetic correlation analyses, and identification of shared single-nucleotide polymorphisms (SNPs).
Individuals with lower baseline eGFR_cys had an increased risk of KSD during a mean follow-up of 13.9 years. However, longitudinal decline in eGFR over time (ΔeGFR_cys) was associated with a reduced risk of KSD (HR 0.80, 95% CI 0.67-0.95). Mendelian randomization analyses showed that genetically predicted lower eGFR (one-sample: OR 0.70, 95% CI 0.63-0.78; two-sample: OR 0.78, 95% CI 0.71-0.85) and CKD (one-sample: OR 0.73, 95% CI 0.65-0.81; two-sample: OR 0.89, 95% CI 0.83-0.97) were associated with a lower risk of KSD. Genetic correlation analyses suggested shared genetic influences between kidney function traits and KSD (eGFR: rg = 0.11; CKD: rg = -0.11). Several shared loci related to calcium homeostasis were identified.
Kidney function decline appears to be associated with a reduced risk of KSD. Combined observational and genetic analyses support shared biological pathways linking these conditions, although further studies are needed to clarify the underlying mechanisms.
Renal failure. 2026 Apr 19 [Epub]
Chi Yuan, Linna Sha, Baoyun Xue, Xia Jiang, Zhongyu Jian
Department of Pediatric Surgery, Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China., Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China., Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China.