during an interview pharmacy timesprofessor of medicine Nelson Liang, MD, Consultants from the Department of Internal Medicine Nephrology and Hypertension and Department of Hematology noted the importance of understanding and managing renal disease in relation to hematological malignancies and drug therapy. Liang also highlighted advances in treatments and potential research directions. He will speak on the panel “Thrombotic Microangiopathies: Drugs and Cancer” during ASN Kidney Week in Philadelphia, PA (November 2, 2023 – November 5, 2023).
pharmacy times: What drugs and cancer types are known to cause thrombotic microangiopathy (TMA), and what impact do they have on kidney health?
Nelson Liang: This is a very good question. There are actually many different cancer types that can cause TMA; however, the most common are mucin-producing cancers, such as gastrointestinal cancers or breast cancer. In terms of medications, many different medications are associated with TMA. The most common anticancer drug is gemcitabine. Now, unfortunately, gemcitabine is used to treat many different cancer types, so you’ll find that it’s actually very common.
Another class of drugs commonly associated with TMA are vascular endothelial growth factor (VEGF) inhibitors and various tyrosine kinase inhibitors. They have a direct mechanism leading to renal injury and TMA through destruction of VEGF.
Another common class of drugs that cause TMA are proteasome inhibitors used to treat multiple myeloma, especially among the three proteasome inhibitors (ixazomib, bortezomib, and carfilzomib), carfilzomib Fezomib appears to be responsible for most TMAs. Finally, several drugs, such as interferons and ticlopidine, may also cause drug-induced TMA.
pharmacy times: Leukemias and lymphomas are thought to be causes of various kidney pathologies. Can you provide examples of possible renal complications from these hematological malignancies and how these kidney-related problems may arise in patients?
Liang: In fact, renal involvement is not uncommon in patients with leukemias and lymphomas. Usually, in leukemia, complications arise through direct infiltration of the leukemia into the kidneys.In Lymphoma, Causes of Kidney Damage [are] More complex. Of course, direct infiltration can also be seen, but unlike leukemias, lymphomas can produce monoclonal proteins that can damage the kidneys, either through deposition (as in monoclonal gammopathy of renal significance), or the monoclonal proteins can TMA caused by activation of complement. Therefore, multiple different mechanisms may occur leading to acute kidney injury (AKI), and these patients often develop progressive AKI. It may be subtle at first, but certainly some of these patients may develop severe AKI due to TMA or leukemia and lymphoma infiltration.
pharmacy times: What potential advances or research directions do you foresee in this setting, particularly in understanding and managing kidney disease in relation to hematological malignancies and drug therapy? How can these developments further improve patient outcomes and care?
Liang: Yes, there have been huge advances in the treatment of lymphoma and multiple myeloma. In addition to newer drugs, there are now chimeric antigen receptor T-cell therapies as well as immunotherapy with bispecific drugs. Both therapies greatly increased the hematologic response in these patients, and…since renal function recovery depends on the hematologic response, we should seek greater renal responses with new therapies.
I think in addition to advances in hematology, there are developments in glomerular disease that we can take advantage of. Drugs such as complement inhibitors may help reduce renal injury caused by monoclonal immunoglobulin-induced complement activation, and other renoprotective drugs (such as SGLT2 inhibitors) should also be explored in some of these diseases.