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

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.

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 2 years in KSFs, with subsequent telephone follow-up for stone events. A total of 654 KSFs (110 with citrate, 544 without) and 207 controls were included. Outcomes comprised anthropometric indices (body mass index, body roundness index, waist-to-hip ratio), metabolic parameters, urinary relative supersaturation ratios (RSR), stone recurrence and stone composition.

No evidence for between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes was identified. Anthropometric indices remained stable in both groups. HbA1c rose in non-citrate (NC) but not in citrate (C) group patients. High-density lipoprotein (HDL) cholesterol increased in both groups, while low-density lipoprotein (LDL) decreased only in C patients. Propensity score-matched analyses showed no between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes, with only modest within-group changes in the C group (hemoglobin A1c, 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.

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.