| Title: | Kidney function decline and kidney stone risk: cohort and Mendelian randomization analyses |
| Journal: | Renal Failure |
| Published: | 19 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42002888/ |
| DOI: | https://doi.org/10.1080/0886022x.2026.2641919 |
Publication 17942
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
OBJECTIVES: To investigate the association and potential causal effect of kidney function decline on kidney stone disease (KSD).</p>
METHODS: 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).</p>
RESULTS: 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.</p>
CONCLUSIONS: 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.</p>
15 Keywords
- Adult
- Aged
- Female
- Genome-Wide Association Study
- Glomerular Filtration Rate
- Humans
- Kidney Calculi
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Prospective Studies
- Renal Insufficiency, Chronic
- Risk Factors
- United Kingdom
5 Authors
- Chi Yuan
- Linna Sha
- Baoyun Xue
- Xia Jiang
- Zhongyu Jian
Enabling scientific discoveries that improve human health