Hammouri Dana, Orwick Andrew, Doll Mark A, Sanchez Vega Dianet, Shah Parag P, Clarke Christopher J, Clem Brian, Beverly Levi J, Siskind Leah J
Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville School of Medicine, Louisville, Kentucky, United States.
Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, United States.
Am J Physiol Renal Physiol. 2025 Feb 1;328(2):F272-F288. doi: 10.1152/ajprenal.00264.2024. Epub 2024 Dec 16.
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. Patients with cancer frequently experience kidney complications, often attributed to antineoplastic therapies. This emphasis on therapy-induced nephrotoxicity has led to the underestimation of the impact of cancer on the kidney. Our study demonstrates that distant organ cancer is sufficient to induce nephrotoxicity, highlighting the existence of cancer-kidney crosstalk. Our findings underscore a gap in our understanding of renal complications in patients with cancer and provide a rationale for identifying the underlying mechanisms for the development of nephroprotective agents.
约30%的癌症患者会出现肾脏并发症，这会妨碍癌症的最佳治疗，给患者的生活质量和医疗系统带来负担。癌症患者肾脏并发症的病因通常归因于肿瘤治疗。然而，癌症对肾脏健康的直接影响被低估了。我们之前的研究表明，转移性肺癌会对肾脏产生不利影响，并加剧化疗引起的肾毒性，这表明肺癌与肾脏之间存在相互作用。本研究旨在探讨这种现象是否特定于所采用的癌症模型。向不同品系的雌性和雄性小鼠注射远处器官癌症的不同细胞系，并对其肾脏组织进行毒性和纤维化分析。癌症对肾脏的影响因癌症类型而异。乳腺癌和肺癌的特定亚型，包括KRAS和表皮生长因子受体（EGFR）突变型癌症，会以依赖于细胞系转移潜能的方式在病理上改变肾脏的生理和功能。这与小鼠品系、性别和癌细胞系来源无关。此外，在肾脏组织中未检测到肿瘤DNA，排除了肾脏转移作为观察到的病理改变的致病因素。无论肿瘤大小，Lewis肺癌和B16黑色素瘤均未引起肾毒性。我们的结果证实了特定癌症类型中癌症与肾脏之间的相互作用。在精准医学时代，进一步的研究对于识别高危肿瘤人群至关重要，以便能够早期发现和管理肾脏并发症。癌症患者经常出现肾脏并发症，通常归因于抗肿瘤治疗。对治疗引起的肾毒性的这种强调导致了对癌症对肾脏影响的低估。我们的研究表明，远处器官癌症足以诱导肾毒性，突出了癌症与肾脏之间相互作用的存在。我们的发现强调了我们对癌症患者肾脏并发症理解上的差距，并为确定肾保护剂开发的潜在机制提供了理论依据。
