Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review

Our plain-English summary of Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review, by T. Zattera, F. Londrino, M. Trezzi, et al (Journal of Nephropathology, 2017).

The study

• Authors: T. Zattera, F. Londrino, M. Trezzi, R. Palumbo, A. Granata, P. Tatangelo, V. Corbani, V. Falqui, N. Chiappini, L. Mathiasen, M. Cavallini, D. Rolla
• Journal: Journal of Nephropathology
• Published: 2017;6(2):43-48
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pemetrexed (PEM) is a new-generation multitargeted antifolate agent with a demonstrated broad-spectrum activity in several types of human cancers, including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known; however, its frequency is considered to be low.

Case Presentation: Here we report two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2) in patients with NSCLC. The first patient required hemodialysis treatment and was submitted to renal biopsy which showed acute tubular damage and interstitial edema without acute tubular necrosis. No other potential nephrotoxic agents were identified. The second patient developed AKI, not proven by biopsy and did not require renal replacement therapy. Both patients, on regular supplementation with folic acid and vitamin B12, concomitantly developed myelosuppression and even several months after PEM withdrawal, showed only a modest improvement of renal function.

Conclusions: PEM is an antifolate antineoplastic agent with a broad-spectrum activity in locally advanced or metastatic NSCLC. It has been shown that PEM allows longer survival. The risk of acute or chronic kidney disease may be one of the prices to be paid for this success.

In plain English

This article described two patient cases and briefly reviewed published cases of kidney damage linked to pemetrexed, a cancer drug used for non-small cell lung cancer and mesothelioma. Both patients were men, aged 52 and 56, with lung adenocarcinoma (not mesothelioma). Both received pemetrexed at 500 mg/m2. The article did not discuss asbestos. In the first man, serum creatinine (a blood marker of kidney function) reached 4 mg/dL after his seventh cycle. A kidney biopsy showed only modest damage to the proximal tubules with mild interstitial edema. He needed hemodialysis, which was stopped after partial recovery, with creatinine at 4.1 mg/dL. The second man was also given carboplatin and paclitaxel. He developed kidney failure during his sixth cycle and had no biopsy. Months later his creatinine was 3 mg/dL. In the published literature since 2003, the authors found 13 cases, including their own, and 8 of them had biopsies. For the second case, they said they could not exclude contributions from other risk factors. The authors concluded that kidney disease may be one of the prices to be paid for the drug's success. They also concluded that creatinine-based estimates could overrate kidney function in cancer patients.

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: Two case reports with a review of published case reports
• Who was studied: Two men, aged 52 and 56, with lung adenocarcinoma (non-small cell lung cancer), cared for in the authors' nephrology departments in Italy around 2009 to 2010
• Exposure: The chemotherapy drug pemetrexed (PEM) at 500 mg/m2 every 21 days. It was given alone in case 1 (after earlier cisplatin and gemcitabine) and with carboplatin and paclitaxel in case 2. No asbestos exposure was studied.
• Main results:
  • Case 1: serum creatinine was 4 mg/dL after the seventh pemetrexed cycle, having been 1 mg/dL in August 2010
  • Case 1: the kidney biopsy showed only modest tubular damage confined to the proximal tubule, with mild interstitial edema
  • Case 1: hemodialysis was stopped after partial recovery (creatinine 4.1 mg/dL, GFR 16 mL/min)
  • Case 2: during the sixth pemetrexed cycle, the patient was admitted with acute non-oliguric kidney impairment, vomiting and pancytopenia (low counts of all blood cell types)
  • Case 2: in December 2009 creatinine was 3 mg/dL and GFR 22 mL/min/1.73 m2
  • Literature review from 2003 onward: 13 cases of proven kidney involvement, including the authors' two, of which 8 had a kidney biopsy
• The authors' conclusion: The authors concluded that acute or chronic kidney disease may be one of the prices of pemetrexed's success in NSCLC, and that estimated GFR could be overrated in cancer patients
• Limitations the authors state:
  • In case 2, the authors could not exclude contributions from other kidney risk factors (dehydration, NSAIDs, radiocontrast agents)

Topics

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Antifolate, Non-Small Cell Lung Cancer, Mesothelioma, Nephrotoxicity, Biopsy, Interstitial, Necrosis.

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