Biomarkers for Diagnosis of Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury among patients who require a kidney biopsy. ATIN is an inflammatory reaction affecting the renal tubulointerstitium that occurs in response to medications, autoimmune diseases, or infections. ATIN is treated by removing the inciting agent and/or initiating immunosuppressive therapy. Kidney biopsy is often required to establish this diagnosis due to lack of pathognomonic clinical features and nonspecific clinical tests but carries a significant bleeding risk and may delay initiation of therapy. Thus, there is an important, unmet need for novel biomarkers that may facilitate the noninvasive diagnosis of ATIN. Since ATIN is characterized by renal tubulointerstitial inflammation, many immune-related soluble factors have been investigated as biomarkers for its diagnosis, including C-X-C motif ligand 9, tumor necrosis factor alpha, interleukin (IL)-9, regulated on activation, normal T cell expressed and secreted, monocyte chemoattractant protein-1, soluble IL-2 receptor alpha, IL-5, Fas receptor, and others. Imaging studies that reflect kidney inflammation have also been investigated. This review highlights the limitations of currently available tests for ATIN, the biomarkers currently under investigation, and the challenges associated with development and validation for their use in clinical practice.