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

Our plain-English summary of Nephrotic syndrome with acute kidney injury due to combination therapy of immune checkpoint inhibitors: a case report and review of the literature, by R. Saiki, K. Katayama, H. Saiki, et al (BMC Nephrology, 2024).

The study

• Authors: R. Saiki, K. Katayama, H. Saiki, A. Fukumori, K. Tsujimoto, M. Yamawaki, F. Tanaka, D. Takahashi, K. Oda, Y. Suzuki, T. Murata, K. Dohi
• Journal: BMC Nephrology
• Published: 2024;25(1):51
• Type of article: Review, Case report
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2024. The Author(s).

In plain English

This article was a case report combined with a review of earlier published cases. It did not discuss asbestos exposure. The authors described a 75-year-old man treated with two immune checkpoint inhibitor drugs, nivolumab and ipilimumab, for malignant pleural mesothelioma. After the first dose he developed nephrotic syndrome (heavy protein loss in the urine) with acute kidney injury. A kidney biopsy showed minimal change disease with mild atherosclerosis and acute interstitial nephritis, with fusion of nearly all podocyte foot processes. The drugs were stopped and corticosteroids were started. He needed hemodialysis, which was stopped after 35 days as his urine output increased. A scan showed that his tumor had shrunk dramatically. The authors attributed the kidney disease to the drugs. Searching PubMed, they found 17 reported cases of this drug-related nephrotic syndrome, including their own. Two of the 17 (11.8%) needed dialysis, and two had received more than one such drug. The authors concluded that combination therapy can make nephrotic syndrome worse than single-drug therapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report with a review of previously published cases found through PubMed searches
• Who was studied: one 75-year-old man with malignant pleural mesothelioma (authors at Mie University, Japan), plus 17 published cases of immune checkpoint inhibitor-related nephrotic syndrome, including this one
• Exposure: the cancer drugs nivolumab (360 mg every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks). The patient had also taken the painkiller loxoprofen sodium for two months. Asbestos exposure was not discussed.
• Main results:
  • The patient's kidney biopsy indicated minimal change disease with mild atherosclerosis and acute interstitial nephritis.
  • Electron microscopy of the patient's biopsy showed fusion of nearly all podocyte foot processes.
  • The patient needed hemodialysis, which was stopped 35 days after it began as his urine output increased.
  • A scan of the patient showed that the tumor had shrunk dramatically.
  • The authors attributed the patient's minimal change disease to the immune checkpoint inhibitors.
  • The literature review identified 17 cases of immune checkpoint inhibitor-related nephrotic syndrome, including this one.
  • Of the 17 cases, 14 were male and 3 female.
  • Of the 17 cases, 7 (41.1%) had minimal change disease and 3 (17.6%) had membranous nephropathy.
  • Of the 17 cases, 2 (11.8%) needed dialysis.
  • Of the 17 cases, 2 had received more than one immune checkpoint inhibitor.
• The authors' conclusion: The authors concluded that, in addition to previously reported risk factors, combination immune checkpoint inhibitor therapy can make nephrotic syndrome worse than single-drug therapy.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immune-Related Adverse Events, Interstitial, Nivolumab (Opdivo), Ipilimumab (Yervoy), Pleural Mesothelioma, Biopsy.

Related studies

• Immune checkpoint inhibitor-induced nephrotic syndrome: a pharmacovigilance analysis of 404 FAERS cases and literature case series — J. Ye, J. Huang, et al. (2025)
• Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors — A. Vogrig, M. Fouret, et al. (2019)
• Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21, -200c, and -423 — M. Pavkovic, C. Robinson-Cohen, et al. (2016)
• Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma — T. Hod, K.J. Freedberg, et al. (2021)
• Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage — G. Rombolà, F. Vaira, et al. (2015)
• Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury — L.F. Liesenfeld, E. Quiring, et al. (2023)

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