Remote Organ Cancer Adversely Alters Kidney Physiology and Induces Kidney Injury and Inflammation

Background: 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 lung cancer adversely alters kidney physiology and function, and chemotherapy-induced nephrotoxicity is exacerbated, indicating cancer-kidney crosstalk. This study examines whether this phenomenon is specific to the employed cancer model. Methods: Mice of various strains were injected with different cell lines representing human and mouse lung cancer, breast cancer, and melanoma. Mice were euthanized upon reaching IACUC protocol endpoints. Kidney tissues were analyzed for toxicity and compared to controls. Results: 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 stage-dependent manner. This was independent of mouse strain, sex, cancer cell delivery route, and cell line origin. Moreover, tumor DNA was not detected in the kidney tissue. Lewis lung carcinoma and melanoma did not cause nephrotoxicity, regardless of the tumor stage. Conclusion: Our results confirm cancer-kidney crosstalk in specific cancer types and highlight gaps in understanding renal complication risk 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. Funding: NIDDK Support