In an interview with pharmacy timesProfessor of Medicine Dr. Nelson Leon, A consultant in both the nephrology/hypertension and hematology divisions of internal medicine, he points out the importance of understanding and managing hematologic malignancies and drug-related kidney disease. Leung also highlights therapeutic advances and potential research directions. He will be speaking on the panel “Thromboscopic Microangiopathy: Drugs and Cancer” during ASN Kidney Week (November 2, 2023 – November 5, 2023) in Philadelphia, Pennsylvania.
pharmacy times: What drugs and cancer types are known to cause thrombotic microangiopathy (TMA) and how do they affect kidney health?
Nelson Leon: That’s a great question. There are actually many different types of cancer that can cause TMA. However, the most common are mucin-producing cancers, such as gastrointestinal tract and breast cancer. Regarding drugs, many different drugs are associated with his TMA. The most common anticancer drug is gemcitabine. Unfortunately, gemcitabine is used for many different types of cancer, which is why it actually turns out to be very common.
Another class of drugs commonly associated with TMAs are vascular endothelial growth factor (VEGF) inhibitors and multityrosine kinase inhibitors. These have a direct mechanism of causing renal injury and TMA through destruction of VEGF.
Another class of drugs that is now commonly seen as a cause of TMA are the proteasome inhibitors used to treat multiple myeloma, particularly the three proteasome inhibitors (ixazomib, bortezomib, and carfilzomib). Of these, carfilzomib appears to cause most TMA. And finally, there are a variety of drugs that can cause drug-induced TMA, such as interferon and ticlopidine.
pharmacy times: Leukemia and lymphoma are among the causes of various kidney lesions. Please give me some examples of kidney complications that can arise from these hematological malignancies and how these kidney-related problems manifest in patients.
Leon: In fact, kidney involvement is not uncommon in patients with leukemia and lymphoma. Usually, with leukemia, complications result from direct invasion of the leukemia into the kidneys.Causes of kidney damage in lymphoma [are] It’s more complicated. Indeed, direct invasion is also seen, but unlike leukemia, lymphomas can produce monoclonal proteins that can damage the kidneys through deposition, as in the case of monoclonal gammaglobulinemia, which is important for the kidneys. monoclonal proteins may activate TMA, which triggers complement. Therefore, many different mechanisms can occur to cause acute kidney injury (AKI), and these patients typically present with progressive AKI. Although it may be subtle at first, certainly some of these patients can develop significant AKI due to TMA or leukemia and lymphoma infiltration.
pharmacy times: What potential advances and research directions do you foresee in this context, particularly in the understanding and management of kidney disease associated with hematologic malignancies and drug therapy? How can we make it even better?
Leon: Yes, there have been great advances in the treatment of multiple myeloma as well as lymphoma. Apart from new drugs, there is now immunotherapy with chimeric antigen receptor T-cell therapy and bispecific therapy. Both of these treatments significantly increased hematologic response in these patients. Since recovery of renal function is dependent on hematological response, greater renal response should be pursued with new treatments.
In addition to advances in the world of hematology, I think there are also developments in the world of glomerular disease that we can take advantage of. They are like complement inhibitors that may help reduce renal damage due to monoclonal immunoglobulin-induced complement activation, and other nephroprotective drugs such as SGLT2 inhibitors may also reduce these effects as well. should be studied in some of the diseases.
