Acute tubular injury versus acute interstitial nephritis in the kidney precision medicine project
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUNDAcute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI), but the diagnosis may be missed as kidney biopsies are rarely obtained when acute tubular injury (ATI) is suspected.METHODSThe Kidney Precision Medicine Project is a cohort study that obtains kidney biopsies from individuals with AKI, which undergo pathologic and molecular interrogation. We compared ATI and AIN cases among the first 60 AKI participants.RESULTSOn clinicopathologic adjudication, 30 patients (50%) had a primary adjudicated diagnosis of ATI, 13 (22%) patients had AIN, 9 (15%) had diabetic nephropathy, and 3 (5%) had other conditions. There were increased interstitial white blood cells and tubulitis (P < 0.05 for both) in AIN compared with ATI. Prior to biopsy, the treating clinician suspected ATI in 83% of the cases with adjudicated ATI, while the treating clinician suspected AIN in 54% of the cases with AIN. Tissue transcriptomic signatures showed enrichment of proinflammatory signaling and increased expression of CXCL9, a chemokine induced by IFN-γ, in myeloid cells of participants with AIN. CXCL9 localized to inflammatory infiltration in spatial transcriptomic data.CONCLUSIONAdjudication of kidney biopsies revealed distinct pathologic and molecular profiles between ATI and AIN. Kidney biopsy should be considered more frequently in AKI, as AIN is clinically underrecognized.TRIAL REGISTRATIONClinicalTrials.gov NCT04334707.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases grants U01DK133081, U01DK133091, U01DK133092, U01DK133093, U01DK133095, U01DK133097, U01DK114866, U01DK114908, U01DK133090, U01DK133113, U01DK133766, U01DK133768, U01DK114907, U01DK114920, U01DK114923, U01DK114933, U24DK114886, UH3DK114926, UH3DK114861, UH3DK114915, and UH3DK114937.
Source: JCI Insight
Authors: Jennifer A. Schaub, Rajasree Menon, Ricardo Melo Ferreira, Elizabeth Kiernan, Insa M. Schmidt, Christine P. Limonte, Soumya Yennapureddy, Ying-Hua Cheng, Leal Herlitz, Avi Z. Rosenberg, Joel M. Henderson, Kelly D. Smith, Jeffrey B. Hodgin, Edgar Otto, Gilbert W. Moeckel, Lloyd G. Cantley, Suman Setty, Ulysses G.J. Balis, Dawit Demeke, Agnes B. Fogo, Andrew S. Bomback, Vivette D. D’Agati, Isaac E. Stillman, Jose R. Torrealba, Allen R. Hendricks, Erika Bracamonte, Vanessa Moreno, Pavan Bhatraju, Amy K. Mottl, Frank C. Brosius, Bijin Thajudeen, Steven G. Coca, Paul M. Palevsky, Parmjeet S. Randhawa, Raghavan Murugan, Laura Barisoni, Charles E. Alpers, Steven Menez, F. Perry Wilson, Dennis G. Moledina, Michael T. Eadon, Matthias Kretzler, Jonathan Himmelfarb, Chirag R. Parikh, the Kidney Precision Medicine Project
Institutions: University of Michigan, Michigan Medicine, Indiana University Indianapolis, Indiana University School of Medicine, University of Washington, Boston University, Boston Medical Center, University Medical Center Hamburg-Eppendorf, Cleveland Clinic, Johns Hopkins University, Beth Israel Deaconess Medical Center, Harvard University, Yale University, University of Illinois Chicago, Vanderbilt University, Vanderbilt University Medical Center, Columbia University Irving Medical Center, Icahn School of Medicine at Mount Sinai, Baylor College of Medicine, The University of Texas Southwestern Medical Center, University of Arizona, University of North Carolina at Chapel Hill, University of Pittsburgh, VA Pittsburgh Healthcare System, Duke University, Johns Hopkins Medicine
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: Harvard Chronic Kidney Disease Research Biopsy Center, G1387720670, G3551404655, Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury (PReCISE AKI), Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury (PReCISE AKI), Kidney Precision Medicine Program (KPMP): Columbia AKI Recruitment Site, G9000234909, Spatial Elucidation of Human Acute Kidney Injury and Chronic Kidney Disease using Imaging Mass Cytometry, PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE), Minnesota Precision Medicine CKD & Resilient Diabetes Recruiting Site: Engagement, Enrollment & Ethics, Integrated spatial interrogation of cellular and molecular signatures of human kidney disease, Single cell multiomic and spatial atlas of acute and chronic kidney injury, Mount Sinai Health System Kidney Precision Medicine Project, University of Illinois at Chicago KPMP CKD Recruitment Site, AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue), Central Hub for Kidney Precision Medicine, Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human Kidney, Boston Chronic Kidney Disease Research Biopsy Center, Cleveland Precision Medicine Chronic Kidney Disease Cohort, Kidney Precision Medicine Project - Patient Engagement, KPMP Kidney Mapping and Atlas Project (KMAP), Geographic and Environmental Health Equity in Kidney Precision Medicine, Spatial Multi-Omics to Profile Metabolic Pathways for Kidney Disease, Spatial Mapping of Proteomic and Transcriptional Signatures in Kidney Disease
OpenAlex ID: W7202245284