What does this research mean for the field?

Long-term citrate treatment in high-risk kidney stone formers does not lead to adverse metabolic effects. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the long-term safety of citrate treatment on metabolic health and stone recurrence in high-risk kidney stone formers.

March 12, 2026Open Access

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

Key Points

To evaluate the long-term safety of citrate treatment on metabolic health and stone recurrence in high-risk kidney stone formers.
Multicenter study within the Swiss Kidney Stone Cohort
Included 654 kidney stone formers and 207 controls
Blood and urine analyses over two years
Telephone follow-up for stone events
Propensity score-matched analyses used to assess differences between groups.
No significant changes in anthropometric, glucose, or lipid outcomes between groups over 1-2 years
Anthropometric indices remained stable
Citrate users showed a 43% stone recurrence rate vs. 30% in non-users
Citrate treatment reduced uric acid supersaturation but did not affect calcium phosphate stones

Abstract

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.

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