A Systematic Review of Immune Checkpoint Inhibitor–Associated Glomerular Disease

Abstract

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Phospholipase A2 receptor antibody mediated membranous nephropathy associated with cemiplimab

“…Majority of glomerular diseases reported have been associated with PD-1/PD-L1 inhibitor use rather than CTLA-4 inhibitor therapy. 4 In our patient, the nephrotic syndrome could be related to the primary malignancy, 5 use of ICI therapy (PD-1 inhibitor) or he could have possibly developed a de-novo glomerular disease. Secondary membranous nephropathy should be considered in patients who develop nephrotic syndrome within 1 year of diagnosis of cancer, particularly in patients who are older than 65 with significant smoking history.…”

“…In a recent systematic review on immune checkpoint inhibitor associated glomerular disease, only 1 out of 45 patients was noted to have membranous nephropathy (PLA2R negative). 4 Our patient developed PLA2R positive membranous nephropathy within 3 months of ICI use making it likely that the two were related. We hypothesize that in our patient, the use of ICI therapy activated the innate immune system leading to production of pro-inflammatory cytokines and an autoimmune humoral response leading to production of PLA2R auto-antibody.…”

“…Majority of glomerular diseases reported have been associated with PD-1/PD-L1 inhibitor use rather than CTLA-4 inhibitor therapy. 4…”

“…3 Glomerular diseases are rarely seen with immunotherapy. 2,4 Furthermore the association of malignancy with some forms of secondary glomerular disease makes it more challenging to distinguish from ICI associated glomerular disease. Current guidelines for the management of kidney immune related adverse events are limited to mainly AIN and not comprehensive due to limited available data and understanding of the physiopathology.…”

Case Report: THSD7A-Positive Membranous Nephropathy Caused by Tislelizumab in a Lung Cancer Patient

“…Among the different types of renal irAEs, acute interstitial nephritis characterized by diffuse interstitial inflammation with a predominant T-lymphocytic infiltrate ( 3 ) was the most common. Glomerular was less affected by immunotherapy, and pauci-immune glomerulonephritis, podocytopathies, and complement 3 glomerulonephritis are the most frequently reported histology subtypes ( 8 ). MN is an antibody-mediated autoimmune glomerular disease ( 9 ) that typically present with marked elevation in urine protein levels and decline in serum albumin levels and is rarely reported to be associated with ICIs therapy ( 10 ).…”