• Feifei Chen, Haiwei Du, and Surong Fang.
• Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
• Medicine (Baltimore). 2023 Jan 20; 102 (3): e32508e32508.

RationaleMembranous nephropathy (MN) is an autoimmune disease, which is classified into primary and secondary MN. Malignancy-associated MN (M-MN) accounts for about 10% of secondary MN cases. Lung cancer is the most common type of malignancy among M-MN patients. Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) have showed promising efficacy and good safety in many types of solid tumors, including non-small cell lung cancer. To date, whether ICIs could be a treatment option for M-MN patients with PD-L1 expression and or high tumor mutation burden (TMB) level has not been documented.Patient ConcernsA 68-year-old male patient presented with edema of the lower limbs with increased urine foam in August 2018. Biopsy on the right kidney showed MN at stage I with subepithelially localized immune deposits.DiagnosisLung squamous cell carcinoma (LSCC)-associated MN with PD-L1 expression (20%) and high TMB level (26.2 mutations/Mb).InterventionsThe patient received immunosuppressive therapy targeting the initially diagnosed primary MN as first-line treatment plus surgery and radiochemotherapy following pembrolizumab targeting the definitively diagnosed lung cancer as second-line treatment.OutcomesThe patient benefited from radiochemotherapy following pembrolizumab (lasting more than 38 months) rather than immunosuppressive therapy.LessonsOur work suggests that combined ICIs might be an effective treatment option for M-MN patients who harbor PD-L1 expression. Our work highlights that the presence of malignancy should not be neglected at the initial diagnosis of MN.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

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