Acute Kidney Injury Results in Long-term Alterations of Kidney Lymphatics in Mice.

The long-term effects of a single episode of acute kidney injury (AKI) induced by bilateral ischemia-reperfusion injury (BIRI) on kidney lymphatic dynamics are not known. The purpose of this study was to determine if alterations in kidney lymphatics are sustained in the long-term and how they relate to inflammation and injury. Mice underwent BIRI as a model of AKI and were followed up to 9 months. While kidney function markers initially normalized, histological analysis revealed sustained tissue damage and inflammation for up to 9 months. Transcriptional analysis showed both acute and late-stage lymphangiogenesis, supported by increased expression of lymphatic markers, with unique signatures at each phase. Expression of Ccl21a was distinctly upregulated during late-stage lymphangiogenesis. Three-dimensional tissue cytometry confirmed increased lymphatic vessel abundance, particularly in the renal cortex, at early and late timepoints post-injury. Additionally, the study identified the formation of tertiary lymphoid structures composed of CCR7⁺ lymphocytes and observed changes in immune cell composition over time, suggesting a complex and dynamic response to AKI involving tissue remodeling and immune cell involvement. These studies provide new insights into the role of lymphatics in the progression of AKI to chronic kidney disease.