Using immunosuppression to treat glomerulonephritis may increase the risk of later developing malignancy after kidney transplantation, a new study finds.

“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,” David Massicotte-Azarniouch, MD, and colleagues from the University of North Carolina at Chapel Hill, wrote.

Patients with glomerulonephritis may be exposed to a variety of immunosuppressant agents, combinations of these agents, and long-lasting treatment with these agents prior to transplantation. These therapies may include corticosteroids, calcineurin inhibitors, cytotoxic therapies, anti-proliferative antimetabolites, and anti-CD20 therapy.

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Dr Massicotte-Azarniouch’s team conducted a retrospective study of kidney transplant recipients attending their center from 2005 to May 2020. A total of 184 patients had glomerulonephritis treated with pretransplant immunosuppression and 579 patients had nondiabetic end-stage kidney disease without pretransplant exposure to immunosuppressants. Among the group with pretransplant immunosuppression for glomerulonephritis, 44.0% had received cyclophosphamide, 16.9% rituximab, 45.1% mycophenolate mofetil, 9.8% azathioprine, 32.6% calcineurin inhibitor, and 92.4% high-dose prednisone.

Over a median 5.7 years of follow-up, a larger proportion of the group with vs without pre-transplant immunosuppression for glomerulonephritis experienced a first solid or hematologic malignancy (13.0% vs 9.7%), Dr Massicotte-Azarniouch and colleagues reported in Nephrology Dialysis Transplantation. Overall, the risk for malignancy was significantly increased 1.8-fold with pretransplant immunosuppression in adjusted analyses. Specifically, use of pretransplant cyclophosphamide and rituximab was significantly associated with a 2.6- and 3.8-fold increased the risk for malignancy, respectively, especially when patients received both agents. The pretransplant median cumulative dose of cyclophosphamide was 6 g and rituximab 2 g. The investigators found no increased malignancy risks with use of calcineurin inhibitors or mycophenolate mofetil.

The risks for nonmelanoma skin cancer and post-transplant lymphoproliferative disorder did not appear any higher with pretransplant immunosuppression, Dr Massicotte-Azarniouch’s team reported.

“Clinicians should be mindful of these risks, in addition to infection risks and medication toxicity, when deciding to continue immunosuppression for [glomerulonephritis], particularly if patients have long-standing impaired kidney function or marked chronicity and fibrosis by kidney biopsy,” Dr Massicotte-Azarniouch and colleagues wrote. “Patients with significant receipt of any type of immunosuppression pre-transplant should also be counseled on the importance of post-transplant monitoring for malignancy.”

Results from this single-center study may be limited by the type of induction and maintenance therapy used to treat glomerulonephritis. Non-T-cell depleting induction was only used by 14%.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Massicotte-Azarniouch D, Detwiler RK, Hu Y, et al. Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis. Nephrol Dial Transplant. Published online December 22, 2022. doi:10.1093/ndt/gfac337