Pembrolizumab induced-C3 glomerulonephritis and RBC cast nephropathy: a case report

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of several cancers. Pembrolizumab is an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody that is approved for the treatment of metastatic non-small cell lung cancer (NSCLC). Pembrolizumab-associated renal toxicity is relatively rare, even in pembrolizumab-associated glomerulonephritis. In this study, we report a rare case of pembrolizumab-induced C3 glomerulonephritis (C3GN) and RBC cast nephropathy. CASE PRESENTATION: A 68-year-old man with NSCLC was receiving treatment with pembrolizumab. After 19 cycles of pembrolizumab therapy, he presented with gross hematuria, severe lower-limb edema and oliguria. Laboratory tests revealed hypoalbuminemia, increased serum creatinine and low serum C3 level. Renal biopsy revealed a typical membranoproliferative glomerulonephritis accompanied by remarkable RBC casts in tubular cavities and tubulointerstitial infiltration of CD8-positive lymphocytes. Based on C3-only immunofluorescence deposit on glomeruli, a diagnosis of C3GN was made. Pembrolizumab was considered the cause of C3GN. Pembrolizumab was discontinued immediately, and 60 mg/day of prednisone was initiated. One dose of cyclophosphamide (400 mg, IV) was also administered. Upon treatment, his symptoms improved rapidly and serum creatinine decreased a lot. However, the patient became dialysis dependent eventually. CONCLUSION: This is the first case of C3GN with RBC cast nephropathy caused by ICIs. This rare case caused by the prolonged use of pembrolizumab further strengthens the relationship between ICIs and C3GN. Thus, periodic evaluation of urine and renal function is recommended in patients receiving pembrolizumab and other ICIs.