# Kidney Injury Molecule-1 in Epithelial Repair > **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $547,940 ## Abstract Project Summary/ Abstract Kidney Injury Molecule-1 (KIM-1) is the most upregulated protein in proximal tubular epithelial cells in various states characterized by epithelial cell dedifferentiation: ischemia, toxic renal injury, and renal cell carcinoma. We have cloned, generated cells and animals expressing wild-type and mutant KIM-1, and created monoclonal and polyclonal antibodies to, human, mouse, rat, pig, dog, and zebrafish KIM-1. We have reported that the KIM-1 ectodomain is cleaved into the blood and urine of subjects with acute (AKI) and chronic (CKD) kidney injury and is a sensitive and specific kidney injury biomarker to detect kidney injury and predict progression of CKD. KIM-1 has been qualified by the FDA for preclinical and clinical use in kidney safety studies. We have discovered that KIM-1 transforms kidney epithelial cells into semiprofessional phagocytes making it the first nonmyeloid phosphatidylserine receptor. We have described a novel phagocytosis pathway that links autophagy to KIM-1-mediated phagosome maturation and MHC restricted antigen presentation in epithelial cells. We have shown that KIM-1 expression in early AKI is adaptive, but chronic expression leads to CKD with severe fibrosis, secondary hypertension, and cardiac hypertrophy. A mouse lacking the extracellular mucin domain, important for phagocytosis, is protected against development of fibrosis. We have found that KIM-1 mediates uptake of palmitate-bound albumin and recently found an inhibitor of KIM-1- mediated phagocytosis by screening a small molecule library. The inhibitor reduces cell lipotoxicity and fibrosis in a novel mouse model of diabetic kidney disease. The current competing renewal application builds upon and extends our prior findings. Our goal is to further characterize KIM-1-mediated uptake of fatty acid bound albumin (FA-Albumin), and the implications of this uptake for cellular injury and maladaptive repair, including cell senescence leading to profibrotic and proinflammatory responses that ultimately lead to progressive CKD. KIM-1 may be a drug target to prevent and treat CKD. We hypothesize that persistent KIM-1-mediated endocytosis of FA-Albumin and subsequent signaling leads to toxicity. FA-Albumin uptake leads to a mitochondrial dysfunction, DNA damage response (DDR), G2/M arrest, mTOR signaling, TASCC formation, and a prosecretory fibrotic phenotype. In addition KIM-1-FA-Albumin uptake leads to chronic tissue inflammation in part due to tertiary lymphoid tissue development through LTaβ/LTβR signaling. In Specific Aim 1 we will characterize binding of KIM-1 to FA-Albumin and determine the architecture, structural dynamics and molecular basis for FA-Albumin binding to KIM-1. In Specific Aim 2 we will characterize the intracellular consequences of KIM-1 mediated FA-Albumin endocytosis, particularly on mitochondrial function, DNA damage, the DDR, cell cycle arrest and the profibrotic secretome. In Specific Aim 3 we will evaluate the role of ... ## Key facts - **NIH application ID:** 10299122 - **Project number:** 2R01DK072381-15 - **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL - **Principal Investigator:** JOSEPH VINCENT BONVENTRE - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $547,940 - **Award type:** 2 - **Project period:** 2005-06-01 → 2026-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10299122 ## Citation > US National Institutes of Health, RePORTER application 10299122, Kidney Injury Molecule-1 in Epithelial Repair (2R01DK072381-15). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10299122. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*