Nephrotic syndrome with acute kidney injury due to combination therapy of immune checkpoint inhibitors: a case report and review of the literature

BMC Nephrol. 2024 Feb 9;25(1):51. doi: 10.1186/s12882-024-03494-1.


Background: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed.

Case presentation: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome.

Conclusions: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy.

Keywords: Acute kidney injury; Immune checkpoint inhibitors; Minimal change disease; Nephrotic syndrome; Nivolumab– ipilimumab.

Publication types

  • Review
  • Case Reports

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / complications
  • Acute Kidney Injury* / therapy
  • Aged
  • Antineoplastic Agents, Immunological* / adverse effects
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Ipilimumab / adverse effects
  • Male
  • Nephritis, Interstitial* / chemically induced
  • Nephritis, Interstitial* / complications
  • Nephrotic Syndrome* / chemically induced
  • Nephrotic Syndrome* / drug therapy
  • Nivolumab / adverse effects


  • Nivolumab
  • Ipilimumab
  • Immune Checkpoint Inhibitors
  • Antineoplastic Agents, Immunological

Supplementary concepts

  • Acute Tubulointerstitial Nephritis