Concomitant Nephrotic Syndrome and Cryoglobulinemia in a Case of Malignant Mesothelioma

Our plain-English summary of Concomitant Nephrotic Syndrome and Cryoglobulinemia in a Case of Malignant Mesothelioma, by K. Nagai, H. Tachi, K. Inoue, et al (Case Reports in Nephrology, 2022).

The study

• Authors: K. Nagai, H. Tachi, K. Inoue, A. Ueda
• Journal: Case Reports in Nephrology
• Published: 2022;2022:8677293
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is rarely associated with nephrotic syndrome. Cryoglobulinemia is found in various pathological statuses, such as hepatitis C virus infection but rarely in malignant neoplasms. We recently encountered a patient with malignant mesothelioma coincident with nephrotic syndrome and cryoglobulinemia in the course of chemotherapy. A 60-year-old man employed as a building painter was diagnosed with malignant mesothelioma by lung biopsy two years earlier and was started on chemotherapy. Nivolumab seemed effective in controlling mesothelioma, but skin immune-related adverse events occurred during the course of treatment. After discontinuation of nivolumab and administration of gemcitabine as an alternative therapy, the patient was referred to a nephrologist because of the subsequent development of edema, renal injury, and proteinuria. Following the investigation, he was diagnosed with nephrotic syndrome and cryoglobulinemia with C4-dominant cold activation. However, a percutaneous renal biopsy could not be performed due to persistent severe cough induced by pleural involvement. The patient died a little over three years after the pathological diagnosis of pleural mesothelioma. Our case had three key features nephrotic syndrome was possibly associated with malignant mesothelioma; cryoglobulinemia occurred in malignant mesothelioma; and concomitant nephrotic syndrome and cryoglobulinemia occurred after chemotherapy. Unfortunately, our rare case lacks a basis in renal pathology or evidence of links between the pathogenesis of malignant mesothelioma, cryoglobulinemia, and nephrotic syndrome. This case does not provide a causal mechanism, but may be worth adding to the case list as one of the rare renal involvement in a patient with malignant mesothelioma.

Copyright © 2022 Kei Nagai et al.

In plain English

This case report described one patient in Japan, a 60-year-old man who worked as a building painter. The article does not mention asbestos exposure. Malignant mesothelioma had been diagnosed by thoracoscopic lung biopsy two years before he was referred to a kidney specialist. He had received cisplatin plus pemetrexed, then carboplatin plus pemetrexed, then nivolumab, which was stopped after skin side effects, then gemcitabine, which was stopped after lung injury. He then developed swelling, kidney injury and heavy urine protein loss (4.3 g/day), with serum albumin of 2.4 g/dL. He was diagnosed with nephrotic syndrome and cryoglobulinemia with low C4 complement. Blood tests excluded chronic hepatitis B and C infection. A kidney biopsy could not be done because of severe cough. After vinorelbine chemotherapy, the nephrotic syndrome improved and the cryoglobulins disappeared. He died a little over three years after his mesothelioma diagnosis. The authors also reviewed 15 earlier published cases of nephrotic syndrome with mesothelioma; none described cryoglobulins. The authors concluded that the case showed no causal mechanism but may be worth adding to the list of rare kidney involvement in mesothelioma.

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 of a single patient, with a review of 15 previously published cases of nephrotic syndrome in malignant mesothelioma
• Who was studied: One 60-year-old man, a building painter, with malignant mesothelioma diagnosed by thoracoscopic lung biopsy, seen at a hospital in Japan (the authors are at Hitachi General Hospital)
• Exposure: The article does not describe any asbestos or fiber exposure. It states only that the patient was a building painter. Before the kidney problems he received cisplatin plus pemetrexed, carboplatin plus pemetrexed, nivolumab and gemcitabine. Vinorelbine was given afterwards.
• Main results:
  • At referral, the patient had massive proteinuria of 4.3 g/day
  • Serum albumin was low at 2.4 (Table 1 gives the unit as g/dL), which the authors took as suggesting nephrotic syndrome
  • Complement levels were C3 170 mg/dL, C4 17 mg/dL and CH50 57 U/mL, which the authors described as suggesting C4-dominant cold activation; cryoglobulins tested positive
  • Chronic hepatitis B and hepatitis C infections were serologically excluded as other causes of secondary cryoglobulinemia (hepatitis B surface antigen negative, anti-HCV antibody negative)
  • The nephrotic syndrome gradually improved with vinorelbine as fifth-line treatment; low C4, cryoglobulinemia and nephrotic-range proteinuria disappeared after vinorelbine
  • A high selectivity of proteinuria (index 0.09) suggested to the authors the possibility of minimal-change disease
  • The patient died a little over 3 years after the pathological diagnosis of mesothelioma, without recurrence of nephrotic syndrome
  • In the authors' review of 15 published cases of nephrotic syndrome with malignant mesothelioma, none described cryoglobulins, and 9 of the 15 cases (60%) involved minimal-change disease
  • The authors suggested that if the nephrotic syndrome and cryoglobulinemia were linked complications of chemotherapy rather than coincidence, the most likely suspect drug was nivolumab, not gemcitabine
• The authors' conclusion: The authors concluded that, to their knowledge, this was the first description of concomitant nephrotic syndrome and cryoglobulinemia in malignant mesothelioma. They stated that although no causal mechanism or pathological findings were identified, the case may be worth adding to the case list as a rare coincidence.
• Limitations the authors state:
  • A kidney biopsy could not be performed because of the patient's condition, so the kidney pathology could not be definitively assessed
  • The case lacked kidney pathology or evidence linking the mechanisms of mesothelioma, cryoglobulinemia and nephrotic syndrome

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Neoplasm, Chemotherapy, Biopsy, Nivolumab (Opdivo), Immune-Related Adverse Events, Gemcitabine.

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