Recurrent acute interstitial nephritis: what lies beneath

Abstract

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.

Management of corticosteroid-dependent eosinophilic interstitial nephritis

“…In a recent retrospective cohort study of 22 patients with recurrent AIN, 2 of 6 patients with DI-AIN underwent MMF treatment. [ 3 ] One patient treated with a corticosteroid followed by MMF showed renal function improvement, whereas another with advanced renal failure showed no response to MMF treatment. These reports suggest a satisfactory tolerability and the steroid-sparing effect of MMF in corticosteroid-dependent DI-AIN.…”

“…This study included two patients with DI-AIN and MMF (1500 mg daily) successfully stabilized serum creatinine levels for over 25 months in both patients without complications. In a recent retrospective cohort study of 22 patients with recurrent AIN, 2 of 6 patients with DI-AIN underwent MMF treatment [3] . One patient treated with a corticosteroid followed by MMF showed renal function improvement, whereas another with advanced renal failure showed no response to MMF treatment.…”

“…However, despite renal recovery after corticosteroid therapy, some patients experience AIN recurrence, thereby exposing them to repeated and long-term corticosteroid administration, which is known as corticosteroid dependency. [ 3 ] Unfortunately, there is little information regarding the management of corticosteroid-dependent eosinophilic interstitial nephritis.…”

“…The main therapeutic strategy for DI-AIN is to discontinue the offending drug; moreover, corticosteroid therapy is initiated in patients with moderate to severe renal injury. However, despite renal recovery after corticosteroid therapy, some patients experience AIN recurrence, thereby exposing them to repeated and long-term corticosteroid administration, which is known as corticosteroid dependency [3] . Unfortunately, there is little information regarding the management of corticosteroid-dependent eosinophilic interstitial nephritis.…”

Infliximab for the treatment of patients with checkpoint inhibitor associated acute tubular interstitial nephritis

“…Relapse of ATIN is also a challenge and associated with worse kidney prognosis. 5 Limited data on the use of steroid-sparing agents (i.e., mycophenolate mofetil or cyclosporin) in cases of steroid-resistant, drug-induced ATIN were successful but pose considerable challenges in cancer patients due to the associated risk of cancer progression and T cell suppression. 6,7 In cases of relapsed CPI-ATIN, GC are frequently re-dosed or reinitiated.…”