Differentiating Acute Interstitial Nephritis from Acute Tubular Injury: A Challenge for Clinicians

Abstract

Background: Differentiating etiologies of acute kidney injury (AKI) is critical in determining the course of care in clinical practice. For example, acute interstitial nephritis (AIN) requires withdrawal of the offending drug and immunosuppressive therapy, while acute tubular injury (ATI) does not have any disease-specific therapies. Failure to distinguish AIN from ATI in a timely manner can lead to kidney fibrosis and chronic kidney disease. In this review, we discuss current tests and novel biomarkers to distinguish ATI from AIN.

Summary: In a prospective cohort study of 32 participants with AIN and 41 with ATI, clinical features and current, laboratory tests did not provide sufficient distinction between the 2 subpopulations of AKI. The findings in our cohort are consistent with our review of the literature. Given the limitations of clinical features and laboratory assessments, clinical practice relies on kidney biopsy for histological diagnosis, which is not always feasible, and is associated with bleeding complications in high-risk populations. In addition, histological diagnosis is prone to sampling errors and inter-rater variability. In the interest of identifying a novel biomarker, we compared urine and plasma levels of cytokines in the Th1, Th2, and Th9 pathways, which have been implicated in the pathogenesis of AIN. Urine TNF-α and interleukin-9 were higher in AIN participants than in ATI controls and helped discriminate AIN from ATI (area under curve 0.83 [0.73-0.92]). Key Messages: Differentiation between AIN and ATI in patients with AKI using currently available tests is challenging. Urine TNF-α and interleukin-9 may help clinicians separate AIN from ATI.

Keywords: Acute renal injury; Fibrosis; Kidney; Nephrology.

Figure 1. Tumor necrosis factor-a and interleukin-9 are biomarkers to differentiate acute interstitial nephritis from acute tubular injury

Panel A shows median (horizontal line), 25^th and 75^th percentile (box), and 5^th and 95^th percentile (whiskers) compared between AIN and ATI. Wilcoxon Ranksum test P-values are shown in red. Panel B and C show post-test probability of AIN at various pre-test probabilities at two cut-offs of interleukin (IL)-9.