Inflammatory leucocyte infiltrates are associated with recovery in biopsy-proven acute interstitial nephritis: a 20-year registry-based case series

Abstract

Background Acute interstitial nephritis (AIN) is a renal injury causing renal function deterioration and requiring renal replacement therapy (RRT) in a substantial number of cases. Therapy is based on withdrawal of suspicious causative drugs or the underlying diseases and/or steroid application if renal function is not restored after cessation of the underlying condition. Hard clinical evidence for augmenting steroid therapy is not available. Methods We reviewed the course and diagnosis for >20 years among all 1126 biopsied samples of our tertiary renal centre. Results 49 (4.4%) were diagnosed with primary AIN, corresponding to an annual incidence of 1/100 000 population; 17 out of 49 biopsy-proven AIN patients required short-term or long-term (n = 5) RRT. According to a combined outcome criterion of coming off dialysis and/or reaching serum creatinine <200 µmol/L, 19 patients reached recovery whereas 20 did not. Among 39 patients with a comprehensive clinical and histopathological data set, presence of cortical scars, AIN histological activity (acute leucocyte infiltrates) and proteinuria were baseline parameters discriminating significantly between groups with or without recovery. No associations with the presence of specific drugs were found. Therapeutic use of steroids was associated with a lower probability of recovery (P = 0.008), presumably due to inclusion bias. Conclusions Following our basic finding of the importance of histopathological parameters of acuity associated with recovery, we argue for the inauguration of grading measures to characterize this issue quantitatively and make it usable for future controlled investigations. Finally, we provide a suggestion for a therapeutic algorithm in the management of AIN.

Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis

“…We also found that higher interstitial infiltrate was associated with better kidney function. Such association of interstitial infiltrate with higher eGFR on follow-up was also noted in the Boston Kidney Biopsy Cohort, which included a broad group of kidney pathology diagnoses [36] and in a recent study of 49 patients with AIN [37]. Presence of interstitial infiltrate is a potentially treatable pathology; it could represent responsiveness to immunosuppressive therapy and thus be associated with higher kidney function.…”

Drug-Induced Acute Kidney Injury

“…In fact, patients with AIN lost a median of 11 ml/min per 1.73 m 2 of eGFR from baseline to 6 months after biopsy (94). Greater interstitial fibrosis is associated with lower kidney function recovery, whereas greater interstitial inflammation is associated with improved kidney function recovery and more dialysis discontinuation (83,94,95). Corticosteroids were most beneficial in patients with greater interstitial infiltrate, higher eGFR before biopsy, and higher urine IL-9 levels (83,94).…”

Clinical significance of kidney immune complex deposition in children with acute interstitial nephritis disease

“…AIN is an uncommon cause of AKI in the pediatric population, accounting for 0.87%∼15.7% of AKI in all children [ 1–2 ], and 27% in adults. AIN is usually caused by drugs, while other causes include autoimmune diseases [ 3 ] (systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, IgG4-related immunoglobulin diseases), infections [ 4 ] (Legionella, Leptospira, Streptococcus, Corynebacterium, mycoplasma, hantavirus, measles, Epstein Barr virus, cytomegalovirus, HIV, etc. ), herbal remedies and neoplastic conditions, etc.…”