Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis

Nephrol Dial Transplant. 2023 Aug 31;38(9):2009-2018. doi: 10.1093/ndt/gfac337.

Abstract

Background: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant.

Methods: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD).

Results: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0% vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate.

Conclusion: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.

Keywords: glomerulonephritis; immunosuppression; kidney transplant; malignancy; non-melanomatous skin cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cyclophosphamide
  • Glomerulonephritis* / etiology
  • Hematologic Neoplasms*
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Kidney Transplantation* / adverse effects
  • Lymphoproliferative Disorders* / epidemiology
  • Lymphoproliferative Disorders* / etiology
  • Neoplasms* / complications
  • Neoplasms* / etiology
  • Retrospective Studies
  • Risk Factors
  • Rituximab / adverse effects
  • Transplant Recipients

Substances

  • Rituximab
  • Cyclophosphamide