Pre-transplant immunosuppression for glomerulonephritis linked with greater cancer risk
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Using pre-transplant immunosuppression to treat kidney transplant recipients with glomerulonephritis correlates with an increased risk for developing malignancy after transplant, according to a retrospective study.
Further, data published in Nephrology Dialysis Transplantation revealed patients experienced an increased risk for malignancy when receiving cyclophosphamide or rituximab as their pre-transplant immunosuppression (PTI).
“An often overlooked but potentially important contributor to a kidney transplant patient’s immunosuppressive burden, and thus subsequent malignancy risk, is treatment received prior to kidney transplant. Glomerulonephritis (GN) is a leading cause of end-stage kidney disease, and well represented among individuals receiving a kidney transplant. Patients with GN who eventually undergo kidney transplantation have often been exposed to immunosuppression for treatment of their underlying GN prior to transplant,” David Massicotte-Azarniouch, MD, from the University of North Carolina (UNC) at Chapel Hill, and colleagues wrote. They added, “These prospective candidates with underlying GN can accrue significant immunosuppression exposure prior to transplant, which added to further immunosuppression post-transplant, could potentially increase risk for malignancy after transplant.”
In a single-center, retrospective study, researchers examined data of 763 kidney transplant recipients from 2005 to 2020 to determine risks for malignancy after transplantation in patients treated with immunosuppression for GN before the transplant. Patients were treated at the UNC Hospitals, and data were derived through the solid organ transplant registry at UNC.
Data of 184 kidney transplant recipients with GN and who received PTI were compared to that of 579 control recipients. Forms of PTI included cyclophosphamide, rituximab, mycophenolate and calcineurin inhibitor.
With the receipt of PTI among patients with GN serving as the exposure, researchers considered first occurrence of nonmelanomatous skin cancer (NMSC), solid or hematologic malignancy or post-transplant lymphoproliferative disorder (PTLD) the primary outcomes. Using Wilcoxon two sample test and Fisher’s exact test, researchers identified differences between the GN and control groups.
During a median follow-up of 5.7 years, researchers observed a 13% increased risk for malignancy among patients taking PTI for GN compared with a 9.7% increased risk among controls. However, patients taking PTI for GN experienced a 10.3% increased risk for NMSC, whereas controls experienced a higher risk of 11.4%. Similarly, controls were at a heightened risk for PTLD (3.1%) compared with patients taking PTI for GN (3.3%).
Analyses revealed an increased risk for malignancy among patients who received cyclophosphamide or rituximab, and even more so for patients who received both treatments.
“Clinicians should be mindful of these risks, in addition to infection risks and medication toxicity, when deciding to continue immunosuppression for GN, particularly if patients have long-standing impaired kidney function or marked chronicity and fibrosis by kidney biopsy. Patients with significant receipt of any type of immunosuppression pre-transplant should also be counseled on the importance of post-transplant monitoring for malignancy,” Massicotte-Azarniouch and colleagues wrote. They added, “Transplant registries should capture the use of pre-transplant immunosuppression to further improve our understanding of this problem, particularly as treatments for glomerular diseases continue to evolve.”
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