Clinical features of hypocitraturic kidney stone formers: an observational and retrospective real-life study in an Italian kidney stone center

Low urinary excretion of citrate is a risk factor for calcium nephrolithiasis, but clinical features of hypocitraturic stone formers remain unclear. Therefore, the present study explored clinical characteristics of hypocitraturic stone formers. It retrospectively analysed clinical characteristics of hypocitraturic patients in a series of 668 adult stone formers refering to a stone outpatient clinic in Milan. Hypocitraturic stone formers (n = 227, 34%) had lower excretion of calcium, phosphate, uric acid, sodium, and potassium than normocitraturic patients. Considering quartiles of citrate excretion, patients in the lowest quartile had lower potassium excretion than patients in the other quartiles, lower calcium, sodium and phosphate excretion and serum urate than patients in the two highest quartiles. During a 2-year follow-up stone recurrence occurred in 127 patients (19%) and was more frequent in hypocitraturic than normocitraturic patients (OR 1.6, 95%CI 1.06–2.34, p = 0.024). Logistic regression showed that the highest risk of stone recurrence was in patients who were hypercalciuric, hyperoxaluric and hypocitraturic (OR 9.3, 95%CI 2–44.6, p = 0.005; stone formers without defects as reference group) and in patients having hyperoxaluria and hypocitraturia (OR 4.2, 95%CI 1.2–14.6, p = 0.024). These findings were confirmed in patients treated with citrate supplements during the follow-up. In conclusion, hypocitraturia is a frequent risk factor for nephrolithiasis and may be associated with low excretion of the other substances involved in the lithogenesis. The association of hypocitraturia with hypercalciuria and/or hyperoxaluria is indicative of a marked risk of stone recurrence during a follow-up of two years.