Kidney function decline and kidney stone risk: cohort and Mendelian randomization analyses.

Area of Science:

• Nephrology
• Genetics
• Epidemiology

Background:

• Kidney stone disease (KSD) is a common condition.
• Understanding the relationship between kidney function and KSD is crucial for prevention and treatment.
• Kidney function decline, characterized by decreasing estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), is a significant health concern.

Purpose of the Study:

• To investigate the association between kidney function decline and the risk of developing kidney stone disease (KSD).
• To explore potential causal links using genetic and observational data.
• To identify shared biological pathways between declining kidney function and KSD.

Main Methods:

• Utilized individual-level data from the UK Biobank and summary data from genome-wide association studies (GWAS).
• Employed prospective cohort models, one-sample and two-sample Mendelian randomization (MR) analyses.
• Conducted genetic correlation analyses and identified shared single-nucleotide polymorphisms (SNPs).

Main Results:

• Lower baseline eGFR was associated with increased KSD risk, but longitudinal decline in eGFR (ΔeGFR) was linked to reduced KSD risk.
• Mendelian randomization analyses indicated that genetically predicted lower eGFR and CKD were associated with a lower risk of KSD.
• Genetic correlation analyses revealed shared genetic influences between kidney function (eGFR, CKD) and KSD, with identified shared loci related to calcium homeostasis.

Conclusions:

• Kidney function decline appears to be associated with a reduced risk of KSD.
• Combined observational and genetic evidence supports shared biological pathways between declining kidney function and KSD.
• Further research is necessary to elucidate the precise mechanisms underlying this association.