IgA Nephropathy Secondary to Ipilimumab Use

Abstract

Ipilimumab is a human monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 approved for the treatment of non-small-cell lung cancer (NSCLC) and other malignancies. Despite a high prevalence of other immune-related adverse events (irAEs), checkpoint inhibitor (CPI)-related nephrotoxicity has been reported less frequently. In this clinical case report, we describe the evaluation of a 70-year-old female with stage IV NSCLC who presented with nephrotic range proteinuria 4 weeks after receiving her first cycle of ipilimumab. She underwent a renal biopsy and was found to have IgA nephropathy that was presumed to be secondary to ipilimumab use, given recent initiation of therapy and clinical history. Unfortunately, despite prompt initiation of corticosteroids, her acute kidney injury progressed and she required hemodialysis, later transitioning to hospice. To our knowledge, this is one of few reported cases of IgA nephropathy secondary to CPI use. With increasing use of CPIs, this case further emphasizes the need for continued surveillance for irAEs, which can occur at any point in a patient’s treatment course.

Small-vessel vasculitis leading to severe acute kidney injury after ipilimumab: a case report

“…However, contrary to previously reported cases, where a pauci-immune ANCA-negative pattern prevails [14,16,17], immunofluorescence was positive for IgM, C3 and C1q in arterial walls. There are previous reports of ICPi-induced kidney injury with immune deposits on biopsy, ranging from an IgA nephropathy to a lupus-like disease, however, this case is unique in that there is intense perivascular inflammation with granulomas and small-vessel vasculitis with glomerular sparing suggesting in situ antigen-antibody complexes formation over deposition of circulating immune complexes that usually lead to glomerulonephritis [18,19]. In conclusion, our case suggests that ICPi-induced small-vessel vasculitis may be more complex than initially thought, with a heterogeneity of pathological patterns, not necessarily resulting in pauci-immune small-vessel vasculitis.…”

“…suggesting in situ antigen-antibody complexes formation over deposition of circulating immune complexes that usually lead to glomerulonephritis [18,19]. In conclusion, our case suggests that ICPi-induced small-vessel vasculitis may be more complex than initially thought, with a heterogeneity of pathological patterns, not necessarily resulting in pauci-immune small-vessel vasculitis.…”