Cancer and its treatment may harm the kidney. Likewise, impaired renal function can complicate cancer management and worsen oncologic outcomes. To help clinicians better understand the links between kidney disease and cancer, Jolanta Malyszko, MD, PhD, of the Medical University of Warsaw in Warsaw, Poland, and colleagues published a new review article in The Lancet. Here are some of the highlights.
Acute Kidney Injury and Cancer
It’s well known that cancer can cause acute kidney injury (AKI) when cancerous cells obstruct the urinary tract, infiltrate the kidney, or provoke hypercalcemia, according to the authors. A growing number of chemotherapeutic agents, however, may also injure the kidneys when they provoke thrombotic microangiopathy, interstitial nephritis, or tubular damage, or result in side effects such as nausea, vomiting, and diarrhea leading to fluid loss. Other AKI contributors in cancer patients include sepsis, contrast use, and nephrotoxic co-medications such as bisphosphonates, nonsteroidal anti-inflammatory drugs (NSAIDs), and some antibiotics, antimycotics, and antiviral drugs.
Chronic Kidney Disease and Cancer
Cancer or its care may increase the likelihood of chronic kidney disease (CKD), and CKD may contribute to cancer development. This combination of comorbidities is associated with reduced survival, the authors noted.
Paraneoplastic glomerulopathies, such as membranous nephropathy, IgA nephropathy, minimal change disease, membranoproliferative glomerulonephritis, and extracapillary glomerulonephritis can lead to CKD in patients with cancer. A subset of patients who undergo radical nephrectomy also later develop kidney disease. CKD occurs in 29% of patients with kidney cancer and 46% of those with bladder cancer, according to the review.
Individuals with end-stage kidney disease are particularly susceptible to malignancy, they stated. Patients on peritoneal dialysis appear to have a higher incidence of bladder and urinary tract cancer, hepatocellular carcinoma, and thyroid cancer than patients on hemodialysis, they pointed out. Some kidney transplant recipients develop Kaposi’s sarcoma and skin cancer.
Nephrotoxicity of Chemotherapeutic Drugs
Systemic chemotherapies can directly or indirectly harm the kidneys. Clinicians need to carefully monitor the dose and duration of use. Cisplatin, for example, can cause AKI in 20% to 30% of cases. Many other conventional agents also can contribute to nephrotoxicity. These agents include methotrexate, gemcitabine, mitomycin C, ifosfamide, pemetrexed, antimetabolites, and nitrosoureas.
Targeted cancer agents such as anti-vascular endothelial growth factor (anti-VEGF) drugs, tyrosine kinase and multikinase inhibitors, epidermal growth factor receptor (EGFR) inhibitors, BRAF inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, and rituximab can also harm the kidneys.
Hormonal therapies and antiresorption agents used in cancer care are also associated with kidney injury. Androgen deprivation therapy (ADT) used to treat prostate cancer may increase AKI risk, especially when luteinizing hormone-releasing hormone agonists are combined with antiandrogens, Dr Malyszko and her coauthors observed. Use of denosumab, a monoclonal antibody that treats skeletal metastases, may result in hypocalcemia. Bisphosphonates are nephrotoxic and may cause acute tubular necrosis, podocyte damage with collapsing focal segmental glomerulosclerosis, or thrombotic microangiopathy.
Immunomodulators and immunotherapy have been linked with adverse effects on the kidneys. Among immune checkpoint inhibitors, use of nivolumab, an anti-PDL-1 monoclonal antibody, can result in hypophosphatemia, proteinuria, and hypertension. Pembrolizumab, an anti-PD-1 monoclonal antibody, can cause acute interstitial nephritis and, rarely, AKI. Ipilimumab, an anti-CTLA-4 antibody, infrequently leads to nephrotic syndrome, acute tubular necrosis, acute interstitial nephritis, and AKI. Chimeric antigen receptor (CAR) T-cell infusion may lead to reversible AKI in several ways, such as when cytokine release syndrome leads to reduced renal perfusion, the authors explained.
Recombinant human interleukin-2 (IL-2) can cause capillary leak syndrome with hypovolemia and AKI. Recombinant interferon-α (IFN-α) can induce proteinuria or even nephrotic syndrome.
“The advances in cancer management present new opportunities and challenges for the oncology and nephrology communities,” Dr Malyszko and her collaborators wrote. “Nephrologists should be informed and actively involved in certain facets of cancer care; a better understanding of cancer biology and cancer therapy is required for nephrologists to become valuable members of the cancer-care team and to provide the best nephrology care possible.”
To aid clinicians, the review includes a useful chart of anticancer agents, possible effects on the kidney, preventive measures, and treatments.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Malyszko J, Tesarova P, Capasso G, Capasso A. The link between kidney disease and cancer: complications and treatment. Lancet. 396:277-287. doi:10.1016/S0140-6736(20)30540-7