Factors associated with de novo urolithiasis after kidney transplantation: a matched case-control study

Abstract

Objective To investigate the clinical characteristics and potential risk factors for de novo urolithiasis in recipients after kidney transplantation. Methods We retrospectively screened a source cohort of 2,301 kidney transplant recipients undergoing longitudinal follow-up between January 2015 and December 2025. Forty recipients who developed de novo post-transplant urolithiasis were identified. For each recipient who developed a stone, the date of first stone diagnosis was defined as the index date. Controls who had undergone transplantation and remained under follow-up without detected stones at the corresponding index date were selected using chronological risk-set matching at a maximum 1:2 ratio. Thirty-seven cases were matched to 74 controls. Laboratory exposures were summarized using available baseline/pre-index measurements. Covariate balance was assessed using standardized mean differences (SMDs). The primary analysis used conditional logistic regression, with Firth bias-reduced conditional logistic regression as a sensitivity analysis. Results Among 2,301 recipients, 40 developed de novo post-transplant urolithiasis, corresponding to an observed cumulative proportion of 1.74%. The median time from transplantation to first stone diagnosis was 341.5 days (interquartile range, 41.0–1,931.5 days). After risk-set matching, excellent covariate balance was achieved across all matched variables (maximum absolute SMD = 0.037). Standard conditional logistic regression revealed that higher baseline serum urate was significantly associated with an increased risk of de novo urolithiasis [odds ratio (OR) 1.72 per 50 μmol/L increase, 95% CI 1.17–2.54; P = 0.006], whereas higher serum phosphate exhibited an inverse association (OR 0.77 per 0.1 mmol/L increase, 95% CI 0.62–0.95; P = 0.016). Firth sensitivity analysis confirmed these findings for serum urate (OR 1.64, 95% CI 1.13–2.38; P = 0.009) and serum phosphate (OR 0.79, 95% CI 0.65–0.97; P = 0.025). Urinary white blood cell (WBC) count showed a strong exploratory association (OR 2.71 per log2 doubling, 95% CI 1.59–4.63; P < 0.001), though the model exhibited near-separation. Conclusions Elevated serum urate is consistently associated with an increased risk of de novo urolithiasis following kidney transplantation. Lower serum phosphate represents a potential secondary metabolic signal requiring further validation. While urinary leukocyturia strongly correlated with stone status in exploratory models, it should be interpreted cautiously and not regarded as a definitive causal factor or surrogate for culture-confirmed urinary tract infection.