Oxalate is a toxic waste product in humans, capable of complexing with calcium to form kidney stones. While some oxalate is consumed in the diet, there are endogenous sources in humans. This review compiles known endogenous sources of urinary oxalate. PubMed and Embase databases were searched, as well as backward citations, for relevant articles published in English. The search strategy relied on terms related to endogenous synthesis and metabolic tracing. Title/abstract review was performed, and articles were excluded from full review if they did not report data on human sources of endogenous oxalate. Risk of bias was assessed using a modified JBI checklist. Weighted averaging was used to combine results and predict endogenous oxalate production. Of 228 unique articles identified, 23 were eligible and included in this study. Total endogenous oxalate production was reported by 7 of the papers, representing 305 healthy subjects. Weighted mean of endogenous oxalate production was 23.8mg/day (95% CI 23-24.6mg/day) with a range of 17-34mg/day. Daily turnover from the metabolic pool of ascorbic acid may account for up to 40% - 60% of total endogenous oxalate production. Other contributors include hydroxyproline (~ 15%), glycine (< 10%), and glycolate (~ 4%). Phenylalanine (< 0.7%), and fructose (negligible) contribute minimally. This review highlights that daily turnover from the metabolic pool of ascorbic acid is the primary source of endogenous oxalate. However, current estimates rely on highly variable data dating back nearly 70 years. Future research using modern metabolomics is required to re-characterize this pathway.

Potassium citrate is widely used as oral alkali therapy for the prevention of recurrent nephrolithiasis. Despite its long-standing clinical use, systematically collected real-world safety data remain limited. We performed a pharmacovigilance analysis to characterize adverse event reports associated with potassium citrate using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS reports submitted between 2014 and 2025 listing potassium citrate as the primary suspect drug were analyzed. Duplicate records were removed, and adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) at both the system organ class and standardized event term levels (preferred terms, PTs). Disproportionality analyses were conducted using reporting odds ratio, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker methods. A total of 408 unique reports were included. Most reports involved adults and were physician-reported from the United States. Disproportionality analysis identified potential safety issues (signals), defined as drug event associations reported more frequently than expected in FAERS and therefore warranting further evaluation, although not establishing causality. The strongest associations involved product-related issues, laboratory investigations, and gastrointestinal disorders. When these potential safety issues were described using standardized MedDRA event terms most reflected formulation- and administration-related problems, including tablet residue in stool, abnormal solubility, swallowing difficulty, throat irritation, and foreign body sensations. Reports of rash were infrequent. This first FAERS-based analysis of potassium citrate highlights that most reported adverse events are related to formulation and administration characteristics rather than drug toxicity. These findings support the overall tolerability of potassium citrate while underscoring the importance of adherence, patient education, and formulation-specific considerations in clinical practice. As a spontaneous reporting system, FAERS is valuable for hypothesis generation, label expansion, and post-marketing surveillance, but it is not suitable for estimating the incidence or absolute risk of adverse events.

This case-control study investigated the association between calcium-sensing receptor (CaSR) gene polymorphisms and calcium-containing kidney stone susceptibility in 100 patients and 100 matched healthy controls from the Kunming Han Chinese population. Genotyping of three CaSR loci (rs1042636, rs1801725, and rs1801726) was performed using SNaPshot technology. The rs1801725 GT genotype significantly increased stone formation risk (odds ratio = 1.50, 95% confidence interval: 1.10-2.00, P = 0.042) and was associated with elevated 24-hour urinary calcium excretion compared with controls (10.683 ± 2.535 vs. 7.436 ± 1.742 mmol/24h, P = 0.002), suggesting impaired renal tubular calcium reabsorption as the underlying mechanism. No significant association was found for rs1042636, while rs1801726 exhibited complete monomorphism (100% CC genotype) across all samples. This study provides the first evidence that the CaSR rs1801725 GT genotype serves as an independent genetic risk marker for urinary calcium stones in the Kunming Han Chinese population. Future research should integrate additional calcium transport pathway genes to develop polygenic risk prediction models and elucidate gene-environment interactions in stone pathogenesis.