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

  • Dana Hammouri
  • , Andrew Orwick
  • , Mark A. Doll
  • , Dianet Sanchez Vega
  • , Parag P. Shah
  • , Christopher J. Clarke
  • , Brian Clem
  • , Levi J. Beverly
  • , Leah J. Siskind
  • University of Louisville

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Approximately 30% of the patients with cancer 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 patients with cancer is often attributed to oncological therapies. However, the direct impact of cancer on kidney health is underestimated. Our previous study demonstrated that metastatic lung cancer adversely alters the kidney 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 of remote organ cancer, 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 epidermal growth factor receptor (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. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.

Original languageEnglish
Pages (from-to)F272-F288
JournalAmerican Journal of Physiology - Renal Physiology
Volume328
Issue number2
DOIs
StatePublished - Feb 2025

Keywords

  • acute kidney injury
  • cancer
  • chronic kidney disease
  • kidney fibrosis
  • onconephrology

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