Abstract

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) is a common cause of acute renal failure affecting between 5% and 27%. It is characterized by the presence of interstitial inflammatory infiltrate, tubulitis and edema. A considerable number of cases develop chronic kidney disease (CKD), with a linear relationship observed with the diagnosis delay. There are different etiologies, most importantly those secondary to drug exposure and those related to immunological diseases. To the date, there are few studies comparing both etiologies. In this regard, the aim of this study is to determine difference between both etiologies by comparing clinical, histological and renal prognosis. METHOD A retrospective, observational, single-center study was performed. Clinical and histological characteristics of patients with a first episode of pharmacological or immunological AIN, confirmed by renal biopsy between 1998 and 2020, were compared. Histological analysis was measured by semi-quantitative methods. RESULTS A total of 67 patients have been described, with a mean age of 68 ± 13 years, 56% were women. The baseline creatinine was 93.8 umol/L with an eGFR (CKD-EPI) of 67 mL/min/1.73 m2; mean follow-up time was 63 ± 55 months. A total of 46 patients presented pharmacological AIN, being NSAIDs and antibiotics the most frequent agents, 21 patients with AIN associated to immunological diseases, being Sjögren’s syndrome the most frequent. Previous CKD was present in both groups, with 42% in immunological AIN versus 32% in pharmacological AIN, of which stage 3a CKD was more frequent in drug-mediated AIN (69% versus 33%) as opposed to stage 3b CKD was more frequent in immunological AIN (67% versus 19%). However, no significant differences were observed in the estimated glomerular filtration rate when comparing both groups. A longer diagnostic delay was observed in patients with immunological, defined as the elapsed time from renal function deterioration to the performance of renal biopsy, 93 ± 210 versus 13 ± 15 days (P = .021). However, creatinine at the time of diagnosis was higher in patients with pharmacological cause (380 ± 199 versus 252 ± 246 umol/L; P = .0002), leukocyturia was more frequent in the pharmacological AIN group without differences in the percentage of hematuria or proteinuria. In histological analysis, there were no significant differences in interstitial infiltrate, renal fibrosis or tubular atrophy. Once the biopsy was performed, treatment was started in all patients before the 5th day. In pharmacological AIN, the causative drug was withdrawn and corticosteroids were administered to the majority of patients. Out of 46 patients, 7 (15%) patients of the pharmacological AIN group, the drug was withdrawn with no additional treatment, 4 of them progressed to end-stage kidney disease (ESKD). In the immunological AIN group, most of patients were treated with corticosteroids or immunosuppressants. Out of 21 patients, 3 patients (14%) were not treated and progressed to ESKD. Treatment time was longer in patients with immunologic AIN (290 ± 195 versus 141 ± 168 days; P = .004). No differences were observed in creatinine or glomerular filtration rate at 6, 12 months, end of treatment or last control. The recovery of renal function was also analyzed, observing a higher percentage of complete recovery in patients with AIN associated with immunological diseases at 6 months (43% versus 24%) and at 12 months of follow-up (58% versus 29%); however, did not reach statistical significance. During follow-up, 2/46 (4%) recurrences were recorded in patients with pharmacological AIN and 6/21 (28%) in the immunological AIN group. CONCLUSION Despite the fact that patients with AIN associated with immunologic disease have a higher rate of previous CKD related to diagnostic delay and a higher rate of relapses, we observed that the evolution/progression of renal function was similar to the patients with pharmacological AIN. This could suggest that immunological AIN has a more favorable clinical course or better response to the treatment.

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