Nephrotic Syndrome During Ipilimumab Plus Nivolumab Therapy for Sarcomatoid Malignant Pleural Mesothelioma: A Case Report of Nivolumab Rechallenge Without Recurrence of Nephrotic Syndrome

Our plain-English summary of Nephrotic Syndrome During Ipilimumab Plus Nivolumab Therapy for Sarcomatoid Malignant Pleural Mesothelioma: A Case Report of Nivolumab Rechallenge Without Recurrence of Nephrotic Syndrome, by K. Shimaya, J. Ota, T. Yasuda, et al (Curēus, 2026).

The study

• Authors: K. Shimaya, J. Ota, T. Yasuda, M. Izumi, S. Endo, Y. Tsukada
• Journal: Curēus
• Published: 2026;18(9):e115962
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Immune checkpoint inhibitor (ICI)-associated nephrotic syndrome is a rare immune-related adverse event. When it occurs during combination ICI therapy, identifying the causative agent and determining an appropriate strategy for subsequent ICI rechallenge can be clinically challenging. A 67-year-old man with unresectable sarcomatoid malignant pleural mesothelioma received combination therapy with ipilimumab and nivolumab, resulting in tumor shrinkage. Approximately four months after treatment initiation, he developed nephrotic syndrome characterized by severe proteinuria, hypoalbuminemia, and bilateral pleural effusions. Both ICIs were discontinued, and prednisolone therapy resulted in improvement of nephrotic syndrome. However, tumor regrowth was observed during corticosteroid tapering, and nivolumab monotherapy was selected for rechallenge. Nephrotic syndrome did not recur after nivolumab rechallenge, which was administered with concurrent prednisolone at a tapering dose. This pattern raises the possibility that ipilimumab alone or the combination of ipilimumab and nivolumab contributed to the development of nephrotic syndrome. This case provides clinical insight into the potential contribution of individual ICIs to ICI-associated nephrotic syndrome and into selective ICI rechallenge as a subsequent treatment strategy.

Copyright © 2026, Shimaya et al.

In plain English

This case report described one patient: a 67-year-old man with type 2 diabetes and unresectable sarcomatoid malignant pleural mesothelioma. The article did not discuss asbestos exposure. The patient received first-line ipilimumab plus nivolumab, two immune checkpoint inhibitor drugs, and the tumors shrank. About four months after treatment began, the patient developed nephrotic syndrome, a kidney disorder. Findings included heavy urine protein loss (protein-to-creatinine ratio 21.5 g/gCr), low blood albumin (1.6 g/dL) and fluid around both lungs. Both drugs were stopped, and a kidney biopsy was not done. Prednisolone, a steroid, improved the kidney findings. When the tumor regrew, nivolumab alone was restarted while the patient was still taking prednisolone 20 mg/day. Nephrotic syndrome did not return, although the tumor gradually progressed. The authors concluded that the course raised the possibility that ipilimumab, or the combination, contributed, but could not establish the cause. They noted that the ongoing steroid may have prevented recurrence, and that the missing biopsy and mild urine protein before treatment were limitations.

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 (single patient)
• Who was studied: One 67-year-old man with type 2 diabetes mellitus and sarcomatoid malignant pleural mesothelioma, who presented with right-sided chest pain in March 2025; the authors are from Soka Municipal Hospital, Japan
• Exposure: The exposure studied was drug treatment, not asbestos: first-line ipilimumab (1 mg/kg every six weeks) plus nivolumab (360 mg every three weeks), later followed by nivolumab alone. The article reports no asbestos exposure history.
• Main results:
  • On Day 107 serum albumin had fallen to 1.7 g/dL and nivolumab was withheld; by then the patient had received three doses of ipilimumab and five doses of nivolumab
  • On Day 134 the tumors had shrunk, but pleural effusions had increased on the right and appeared on the left. Serum albumin was 1.6 g/dL, proteinuria was 4+, and the urine protein-to-creatinine ratio was 21.5 g/gCr, consistent with nephrotic syndrome. Serum creatinine was 0.97 mg/dL.
  • Renal biopsy was not performed because of concerns about comorbidities and because consent could not be obtained
  • After prednisolone (50 mg/day) was started on Day 149, the kidney findings improved. By the time the dose was tapered to 20 mg/day, serum albumin was 3.4 g/dL and the urine protein-to-creatinine ratio was 0.8 g/gCr.
  • Because of tumor regrowth, nivolumab alone was restarted on Day 216 while prednisolone continued at 20 mg/day. Ipilimumab was not reintroduced.
  • During nivolumab monotherapy, nephrotic syndrome did not recur, but the tumor gradually progressed. Bacterial pneumonia after two doses temporarily interrupted treatment. After further progression on Day 355, treatment was switched to pemetrexed.
• The authors' conclusion: The authors concluded that the clinical course cannot establish ipilimumab as the cause of the nephrotic syndrome, but provides insight into its potential contribution. They added that the steroid given during rechallenge may have contributed to the absence of recurrence.
• Limitations the authors state:
  • No renal biopsy was done, and protein was present in the urine before treatment; together these prevent a definite causal link between the drugs and the nephrotic syndrome
  • Ongoing prednisolone at 20 mg/day during nivolumab rechallenge may have prevented recurrence
  • Absence of recurrence does not rule out a role for nivolumab, because immune-related adverse events do not always recur on re-exposure
  • Pre-existing kidney disease such as diabetic nephropathy could not be excluded

Topics

Medical terms in this study, explained in our Lexicon: Ipilimumab (Yervoy), Nivolumab (Opdivo), Sarcomatoid, Pleural Mesothelioma, checkpoint inhibitors, Unresectable, Bilateral, Pleural Effusion.

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