Long-term citrate treatment in high-risk kidney stone formers is not associated with metabolic adverse effects

Abstract Background Citrate is frequently applied in kidney stone formers (KSFs), yet long-term safety data are lacking. We evaluated the effects of prolonged citrate therapy on metabolic health, urinary risk factors, and stone recurrence in high-risk KSFs in Switzerland. Methods The Swiss Kidney Stone Cohort (SKSC) is a multicenter study including KSFs and controls. Blood and urine analyses were performed at baseline and longitudinally over two years in KSFs, with subsequent telephone follow-up for stone events. 654 KSFs (110 with citrate, 544 without) and 207 controls were included. Outcomes comprised anthropometric indices (BMI, body roundness index, waist-to-hip ratio), metabolic parameters, urinary relative supersaturation ratios (RSR), stone recurrence, and stone composition. Results No evidence for between-group differences in 1–2-year changes in anthropometric, glucose, or lipid outcomes was identified. Anthropometric indices remained stable in both groups. HbA1c rose in NC but not in C patients. HDL cholesterol increased in both groups, while LDL decreased only in C patients. Propensity score–matched analyses showed no between-group differences in 1–2-year changes in anthropometric, glucose, or lipid outcomes, with only modest within-group changes in the C group (HbA1c, HDL and LDL cholesterol). Urine analyses showed a greater reduction in RSR for brushite among NC patients, whereas C patients had a stronger decline in uric acid (UA) RSR. Calcium oxalate RSR decreased similarly across groups. Stone recurrence was more frequent in C patients, with 43% versus 30% of NC patients changing stone type during follow-up. No shift toward calcium phosphate stones was observed in citrate users. Conclusions Long-term citrate therapy appeared metabolically safe, and selectively reduced UA supersaturation, while non-treated patients showed a more pronounced decrease for brushite. Higher recurrence among treated patients may reflect different baseline risk. A prospective trial is warranted to clarify additive benefits of citrate beyond dietary-guided counseling.