Methotrexate-induced nephrogenic diabetes insipidus: first case report

Sir, Methotrexate (MTX) has become the dominant second‐line agent in the treatment of patients with rheumatoid arthritis (RA). Several studies have shown that MTX has a very good long‐term safety profile, and renal toxicity is very rare [1, 2]. We report a case of renal toxicity induced by MTX that provides the first description of MTX‐induced nephrogenic diabetes insipidus in a patient with RA. A 39‐yr‐old male with no previous nephropathy and a 4‐yr history of RA was receiving 12.5 mg MTX weekly and non‐steroidal anti‐inflammatory drugs (NSAIDs), with a very good clinical response. Six weeks after the initiation of MTX therapy, he experienced polydipsia, nocturia and polyuria (urine output around 9 l/day). The complete blood cell count, renal function (measured by plasma creatinine concentration and creatinine clearance) and sodium, urea and other solutes were within normal limits. Examination of the urine revealed no trace of proteins or cells but osmolality on the low normal range (140 mOsm/kg). Diabetes insipidus (DI) was then suspected and a standard fluid deprivation test was done. During 8 h of water deprivation, urine osmolality did not exceed 300 mOsm/kg. When antidiuretic hormone was given (5 units subcutaneously), urine osmolality increased by about 40% (increase of 38% after 4 h). Magnetic resonance imaging of the brain excluded pituitary abnormalities.