Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed

Our plain-English summary of Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed, by M. Assayag, P. Rouvier, M. Gauthier, et al (BMC Cancer, 2017).

The study

• Authors: M. Assayag, P. Rouvier, M. Gauthier, G. Costel, P. Cluzel, L. Mercadal, G. Deray, C. Isnard Bagnis
• Journal: BMC Cancer
• Published: 2017;17(1):770
• Type of article: Case report
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients.

Case Presentation: We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m2), then followed by Taxol.

Conclusions: The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m2 is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.

In plain English

This was a case report from a Paris hospital about kidney damage during chemotherapy. It did not concern asbestos. Pemetrexed, one of the drugs given, is also used for malignant mesothelioma. The patient, a 66-year-old woman, had stage IV lung adenocarcinoma (not mesothelioma) that had spread to the pleura and lymph nodes. From January 2014 she received cisplatin, pemetrexed and bevacizumab. Her plasma creatinine rose from 50 μmol/L before treatment to 92 μmol/L in April 2014. Cisplatin was stopped, but her kidney function kept worsening on pemetrexed and bevacizumab. Chemotherapy was cancelled in December 2014, when creatinine reached 196 μmol/L (estimated GFR 24 ml/min/1.73m2). Creatinine kept rising after treatment stopped. A kidney biopsy showed acute tubular necrosis, with normal glomeruli, interstitium and vessels. Kidney function did not recover. She did not need dialysis until December 2016. She received gemcitabine (5 cycles) in 2015, then gemcitabine and paclitaxel (6 cycles each) in 2016. The authors judged pemetrexed a possible cause, though they noted the mild proteinuria might have pointed to bevacizumab. They concluded that close kidney monitoring in cancer patients is important.

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 66-year-old woman with TNM stage IV lung adenocarcinoma with pleural and nodal metastasis, diagnosed December 2013, admitted to Pitié Salpêtrière Hospital, Paris, in March 2015 for rapidly progressive kidney failure
• Exposure: Chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2) and bevacizumab (10 mg/kg) from January 2014, plus three sessions of external radiotherapy; no asbestos exposure is discussed
• Main results:
  • Before chemotherapy, the patient's plasma creatinine was 50 μmol/L (estimated GFR 113 ml/min/1.73m2).
  • After creatinine rose to 92 μmol/L in April 2014, cisplatin was stopped and only pemetrexed and bevacizumab were continued from June 2014.
  • Chemotherapy was cancelled in December 2014 when creatinine rose to 196 μmol/L (estimated GFR 24 ml/min/1.73m2).
  • After treatment stopped, creatinine continued to rise, to 266 μmol/L in January and 297 μmol/L in February 2015.
  • The kidney biopsy showed acute tubular necrosis. Glomeruli and the interstitial compartment were normal, and immunofluorescence was negative.
  • Kidney function did not recover. GFR stayed low (around 17 ml/min/1.73m2), but the patient did not need dialysis until December 2016.
  • Cancer treatment continued with 5 cycles of gemcitabine in 2015, then 6 cycles of gemcitabine and 6 of paclitaxel in 2016.
  • The lung CT scan was stable at the last visit.
  • The authors considered that the continued decline after cisplatin was stopped tended to rule out platinum salts, and that pemetrexed could be the causative agent.
• The authors' conclusion: The authors concluded that close monitoring of kidney function in cancer patients is important. In their view, anticipating side effects and discussing renal biopsy early may improve the chances of completing therapy.
• Limitations the authors state:
  • The authors noted that in polychemotherapy the causative drug may be difficult to identify. Although they found no thrombotic microangiopathy, the mild proteinuria might have supported a role for bevacizumab.
  • Electron microscopy of the biopsy was not performed.

Topics

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

Related studies

• Folinic Acid Prophylaxis and Dose Adjustments Enable Safe Treatment with Pemetrexed in Patients with Renal Impairment — N. de Rouw, L.S. Otten, et al. (2025)
• 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)
• Rethinking the Application of Pemetrexed for Patients with Renal Impairment: A Pharmacokinetic Analysis — N. de Rouw, R.J. Boosman, et al. (2021)
• Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study — S. Shoji, M. Hosojima, et al. (2019)
• Pharmacokinetically-guided dosing of pemetrexed in a patient with renal impairment and a patient requiring hemodialysis — N. de Rouw, S. Croes, et al. (2019)
• Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin — P. Owusu-Agyemang, R. Arunkumar, et al. (2012)

Browse more research in BMC Cancer, or return to medical research.