Acute Tubular Necrosis and Interstitial Nephritis during Pemetrexed Therapy

Our plain-English summary of Acute Tubular Necrosis and Interstitial Nephritis during Pemetrexed Therapy, by J. Michels, J.P. Spano, I. Brocheriou, et al (Case Reports in Oncology, 2009).

The study

• Authors: J. Michels, J.P. Spano, I. Brocheriou, G. Deray, D. Khayat, H. Izzedine
• Journal: Case Reports in Oncology
• Published: 2009;2(1):53-56
• Type of article: Case report
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy. Despite drug withdrawal, renal function remained altered and the patient experienced chronic renal insufficiency. Pemetrexed disodium (Alimta) is a multitargeted antifolate agent approved by the Food and Drug Administration (FDA) for patients diagnosed with mesothelioma and non-small cell lung cancer. This drug is almost exclusively cleared by renal excretion [1]. The most common side effects are hematologic dose-limiting toxicities and nonhematologic toxicities including fatigue, diarrhea, nausea, mucositis and rash. Although few cases of renal failure have been published, no study has reported on the renal pathological findings in this setting. We present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy.

In plain English

This case report described one patient in Paris: a 53-year-old African man diagnosed in 1993 with undifferentiated carcinoma of unknown primary site. A later biopsy showed large-cell carcinoma of bronchial or thymic origin. The patient did not have mesothelioma, and asbestos is not mentioned. Mesothelioma appears only as background: pemetrexed is approved for it, and the discussion cites kidney problems in other mesothelioma patients given the drug. The patient had previously received several chemotherapy regimens, including cisplatin, and was given pemetrexed again in 2007. Serum creatinine, a blood marker of kidney function, rose from 100 μmol/l at baseline to 400 μmol/l after the sixth cycle. A kidney biopsy showed acute tubular necrosis with chronic interstitial fibrosis. After fluids, urine alkalinisation and folinic acid, the authors reported partial recovery within one month, though the creatinine printed for that point was still 400 μmol/l. Six months later it was stable at 380 μmol/l. The authors concluded that pemetrexed therapy may induce this kidney damage, leading to chronic renal failure. This single case gives no rate. The rates in the discussion come from other studies.

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 53-year-old African man diagnosed in 1993 with unknown primary undifferentiated carcinoma, later biopsied as large-cell carcinoma of bronchial or thymic origin. He was treated at Pitié-Salpêtrière Hospital, Paris, and also had hepatitis B and C virus infections. He did not have mesothelioma.
• Exposure: The cancer drug pemetrexed: 4 cycles in 2005 (stopped because of blood toxicity), then pemetrexed again from April 2007, with kidney failure found after the sixth cycle. He had earlier received cisplatin and other chemotherapy. No asbestos exposure is described.
• Main results:
  • In this patient, serum creatinine rose from 100 μmol/l at baseline to 400 μmol/l after the sixth pemetrexed cycle. Creatinine clearance was 10 ml/min.
  • A 24-hour urine collection showed 0.55 g of protein, without blood or white cells in the urine.
  • The kidney biopsy showed acute tubular necrosis associated with chronic interstitial fibrosis.
  • After intravenous hydration, urine alkalinisation and folinic acid, kidney function was reported as partially recovered within 1 month. The creatinine printed for that point is 400 μmol/l, the same as the value after the sixth cycle.
  • Six months after the acute kidney failure, serum creatinine was stable at 380 μmol/l.
• The authors' conclusion: The authors concluded that pemetrexed therapy may induce acute tubular necrosis with interstitial fibrosis leading to chronic renal failure. They noted that although the patient had previously received cisplatin, the kidney failure appeared only after pemetrexed.

Topics

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

Related studies

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• Prognosis and causes of death of patients with acute exacerbation of fibrosing interstitial lung diseases — J. Salonen, M. Purokivi, et al. (2020)
• Causes of acute respiratory hospitalizations predict survival in fibrosing interstitial lung diseases — J. Salonen, H. Vähänikkilä, et al. (2020)
• Year in review 2011: acute lung injury, interstitial lung diseases, physiology, sleep and lung cancer — K. Takahashi, N.D. Eves, et al. (2012)
• 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)
• Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review — T. Zattera, F. Londrino, et al. (2017)

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