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bioRxiv · 10.1101/2024.07.29.605635

Remote organ cancer adversely alters renal function and induces kidney injury, inflammation, and fibrosis.

Hammouri, D.·Orwick, A.·Doll, M.·Sanchez Vega, D.·Shah, P. P.·Clarke, C. J.·Clem, B.·Beverly, L. J.·Siskind, L. J.
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Abstract

Approximately 30% of cancer patients experience kidney complications, which hinder optimal cancer management, imposing a burden on patients quality of life and the healthcare system. The etiology of kidney complications in cancer patients is often attributed to nephrotoxic oncological therapies. However, the direct impact of cancer on kidney health is underestimated, as most nephrotoxic oncological therapies have been studied in animal models that do not have cancer. Our previous study demonstrated that metastatic lung cancer adversely alters kidney physiology and function, and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. The current study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines representing human and mouse lung cancer, breast cancer, and melanoma, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and EGFR-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types and highlight gaps in understanding the risk of renal complications in cancer patients. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.

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Hammouri, D., Orwick, A., Doll, M., Sanchez Vega, D., Shah, P. P., Clarke, C. J., Clem, B., Beverly, L. J., Siskind, L. J.. 2024-07-30. Remote organ cancer adversely alters renal function and induces kidney injury, inflammation, and fibrosis.. https://doi.org/10.1101/2024.07.29.605635

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