Recurrent acute interstitial nephritis: what lies beneath

BACKGROUND: Acute interstitial nephritis (AIN) is an emerging cause of acute kidney disease. While this disease usually follows an acute course, it may occasionally recur, representing a major challenge for the clinician. METHODS: We performed a retrospective, observational cohort study in 13 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients with biopsy-proven AIN between 1996 and 2018 were included. RESULTS: The study group consisted of 205 patients with AIN, 22 of which developed recurrent AIN (RAIN) after a median of 111 days from diagnosis. RAIN was due to a surreptitious reintroduction of a previously known implicated drug or toxic in six patients (27%), sarcoidosis in two (9%), Sjögren’s syndrome in three (14%), light-chain-mediated AIN in two (9%) and tubulointerstitial nephritis and uveitis syndrome in two (9%), while in the rest of cases (32%), no precise cause could be identified. Microscopic haematuria was more frequent in patients with underlying systemic diseases. The first RAIN episode was treated with a repeated course of corticosteroids in 21 patients (95%). In six cases (27%), azathioprine and mycophenolate mofetil were added as corticosteroid-sparing agents. During a median follow-up of 30 months, 50 patients (27%) with no recurrences and 12 patients (55%) with RAIN reached Stages 4 and 5 chronic kidney disease (CKD). By multivariable logistic regression analysis, RAIN was independently associated with the risk of reaching Stages 4 and 5 CKD, even after adjusting for potential covariables. CONCLUSIONS: RAIN is infrequent but is associated with poor kidney survival. RAIN should prompt clinicians to search for an underlying aetiology other than drug induced. However, in a large percentage of cases, no precise cause can be identified.