Urine Interleukin-9 And Tumor Necrosis Factor-Alpha For Prognosis Of Human Acute Interstitial Nephritis

Background. We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-alpha can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN.Methods. In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-alpha) with estimated glomerular filtration rate measured 6months after diagnosis (6m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6m-eGFR.Results. In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73m(2), respectively. Patients with higher severity of interstitial fibrosis had lower 6m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6m-eGFR. IL-9 levels were associated with lower 6m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73m(2)]. Corticosteroid use was associated with higher 6m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m(2)] only in those with urine IL-9 above the median (>0.66ng/g) but not in others.Conclusions. Urine IL-9 was associated with lower 6m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.