Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

• Published in: Cancer chemotherapy and pharmacology 2021-06, Vol.87 (6), p.723-742
• Main Authors: Mielczarek, Łukasz, Brodziak, Anna, Sobczuk, Paweł, Kawecki, Maciej, Cudnoch-Jędrzejewska, Agnieszka, Czarnecka, Anna M.
• Format: Article
• Language: English
• Subjects: Adverse events; Animals; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Cancer Research; Carcinoma, Renal Cell - drug therapy; Clinical trials; Diabetes mellitus; Drugs; Humans; Hypertension; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - pharmacology; Immunosuppressive agents; Impairment; Inhibitors; Kidney - drug effects; Kidney cancer; Kidney Neoplasms - drug therapy; Kidneys; Kinases; Medicine; Medicine & Public Health; Neoplasms; Oncology; Patients; Pharmacology/Toxicology; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein-tyrosine kinase; Rapamycin; Renal cell carcinoma; Review; Review Article; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; Toxicity; Tyrosine
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-021-04260-y

The introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.