Severe kidney inflammation after pembrolizumab for lung adenocarcinoma

What happened, in summary

A 65-year-old Japanese man was diagnosed with lung adenocarcinoma in August 2020 and began pembrolizumab 4 mg/kg every three weeks. His kidney function was normal before treatment. Hematuria appeared after two cycles, and pembrolizumab was stopped after seven cycles when destructive thyroiditis developed. Over the following months, proteinuria, loss of appetite, inflammation, acute kidney injury, and liver dysfunction emerged. By May 2021, his creatinine had risen to 2.6 mg/dL. Kidney biopsy showed diffuse crescent formation, membranous nephropathy, and acute tubulointerstitial nephritis, consistent with a severe immune-related complication. He received three days of intravenous methylprednisolone followed by oral prednisolone. Kidney function initially worsened but then improved over nine months, with creatinine falling to 1.54 mg/dL and proteinuria decreasing. Prednisolone was tapered to 2.5 mg daily. Cancer care had to be reconsidered after immunotherapy was stopped. In October 2021, CT showed enlargement of the primary lung tumor, and carboplatin plus paclitaxel was started. His course required balancing cancer control with delayed immune-related toxicity, because the kidney injury became clinically significant even after pembrolizumab had been discontinued.