ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: SA-PO212

Clinical and Pathological Analysis of Five Cases of Immune Checkpoint Inhibitor (ICI)-Associated Membranous Nephropathy

Session Information

Category: Onconephrology

  • 1700 Onconephrology


  • Matsumoto, Minami, Kyoto Daigaku, Kyoto, Japan
  • Yamamoto, Shinya, Kyoto Daigaku, Kyoto, Japan
  • Akagi, Ryota, Kyoto Daigaku, Kyoto, Japan
  • Matsubara, Takeshi, Kyoto Daigaku, Kyoto, Japan
  • Yanagita, Motoko, Kyoto Daigaku, Kyoto, Japan

Since ICIs have become a promising approach and have shaped a paradigm shift in tumor therapies, clinicians are increasingly confronted with immune-related adverse events (irAEs). Acute interstitial nephritis (AIN) is the most common renal irAE, and the treatment of ICI-AIN is based on ICI discontinuation and corticosteroids, which, in most cases, leads to recovery. On the other hand, ICI-associated membranous nephropathy (MN) is relatively rare, and its clinical and histological features and treatment remain unclear.

Case Description

We conducted a multicenter study on renal irAEs by the nationwide Onconephrology Consortium in Japan and analyzed five patients with ICI-associated MN. Patients received Nivolumab for NET, lung adenocarcinoma (two patients), ovarian cancer, and renal cell carcinoma. All patients presented with proteinuria after ICI initiation. Three patients responded to ICI discontinuation and immunosuppressive treatment, including corticosteroids and cyclosporine, and finally achieved remission, whereas two patients did not. The time from ICI administration to disease onset was longer (17.6 months) in treatment responders, whereas it was shorter (6 weeks) in patients with persistent proteinuria. Histologically, in all patients, immunofluorescence microscopy showed granular staining in the capillary walls for IgG (IgG1>4) and C3, and negative PLA2R staining, suggesting secondary MN. Two of the three remission cases showed granular staining for nerve epidermal growth factor-like 1 (NELL-1), which is frequently reported in malignancy-associated MN. The remaining remission case showed a lupus-like deposition pattern with high electron dense deposits in the subepithelial, intramembranous, and subendothelial areas. Two patients with persistent massive proteinuria showed negative NELL-1 staining and no dense deposit in subendothelial area.


We revealed that the ICI-MN population is clinically and pathologically heterogeneous, and some patients showed proteinuria remission with treatment. The characteristics of slow-onset and NELL-1-positivity might be predictors of proteinuria remission. Our results speculated that ICI may induce underlying antibodies against tumor antigens such as NELL-1, leading to malignancy-associated MN, or may trigger immune responses, causing lupus-like MN.