Crescentic Fibrillary Glomerulonephritis in the Setting of Immune Checkpoint Inhibitor Therapy: A Report of Two Cases.

Abstract

Introduction: Immune checkpoint inhibitor (ICPI) therapy is used to treat various malignancies; however, it can be associated with off-target effects including kidney injury. Acute tubulointerstitial nephritis is the most commonly described renal pathology associated with ICPIs, although less frequently, glomerulopathies may be identified when a kidney biopsy is performed in the work-up of acute kidney injury (AKI).

Case presentation: Two patients with small cell carcinoma of the lung were treated with etoposide, carboplatin, and the ICPI atezolizumab. During 2 and 1.5 months of atezolizumab therapy, respectively, patients developed AKI, hematuria, and proteinuria, and kidney biopsies were performed. Both biopsies showed fibrillary glomerulonephritis with focal crescentic features. One patient died 5 days after the kidney biopsy, while the second showed improvement of renal function after discontinuation of atezolizumab and initiation of corticosteroid therapy.

Discussion: We describe two cases of fibrillary glomerulonephritis with crescents after administration of atezolizumab. Development of impaired kidney function following initiation of ICPI therapy in both cases raises the possibility that ICPI therapy may potentiate the development of endocapillary proliferation and crescents (i.e., an "active" glomerulitis) via immune modulation. Thus, exacerbation of underlying glomerulonephritis should be kept in the differential diagnosis of patients who develop AKI, proteinuria, and hematuria following ICPI therapy.