Indapamide therapy and hypercalciuric idiopathic calcium nephrolithiasis recurrences

Background – Idiopathic calcium nephrolithiasis (ICN) is a high-prevalence disease characterized by high recurrence rate. Hypercalciuria (>4 mg/kg/24h) is the main urinary risk factor. Indapamide, a thiazide-like diuretic, can be an effective treatment for lowering calcium excretion, although some subjects may still experience recurrences. The reasons of these therapeutical failures are still poorly known. Aims – Our aim was to evaluate urinary factors linked to kidney stone recurrences on indapamide therapy, the minimum effective indapamide dose and the effect of concurrent therapies. Methods – At the Stone Clinic of Parma University Hospital, Italy, we retrospectively evaluated all the clinical records from 1987 to 2012 of patients with ICN, hypercalciuria, at least one stone relapse, treated with indapamide and subdued to a full urinary profile of lithogenic risk (comprehensive of 24-hour urinary calcium, sodium, oxalate, phosphorus, ammonium, citrate and potassium excretion) before and after treatment. We collected urinary data, concurrent therapies (i.e. potassium citrate or allopurinol), indapamide dose (2.5 mg/day or 1.5 mg/day) and possible follow-up recurrences. Data were analyzed with multivariate statistic, binary logistic regression and discriminating analysis where appropriate. Results –68 patients (48M, age 46±10) responded to inclusion criteria. Mean follow-up period was 13 months. 11 patients (6M) had recurrences during follow-up, showing significantly higher values of ammonium (46±12 vs 37±11 mEq/24h, p=0.023) and sodium (208±62 vs 167±75 mEq/24h, p=0.045) excretion than non-recurrent patients in the follow-up lithogenic profile. Discriminating analysis confirmed that high follow-up sodiuria and ammoniuria are predictive of recurrences on indapamide therapy (standardized canonical coefficient >0.2, p=0.007). Concurrent treatment with potassium citrate or allopurinol did not affect the risk of recurrence. Indapamide was equally effective in lowering calciuria both at high doses (2.5 mg/day, 23 patients, calciuria 462 ± 145 vs 301 ± 155 mg/24h, p<0.001) and at low doses (1.5 mg/day, 45 patients, calciuria 453±116 vs 293±119 mg/24h, p<0.001). Conclusions – A high urinary ammonium and sodium excretion, indexes respectively of animal protein and salt intake, can be major predictors of recurrence in patients with ICN and hypercalciuria on indapamide therapy. Indapamide is anyway an effective therapy for lowering calcium excretion in recurrent ICN at any dosage.