Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage

Our plain-English summary of Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage, by G. Rombolà, F. Vaira, M. Trezzi, et al (Journal of Nephrology, 2015).

The study

• Authors: G. Rombolà, F. Vaira, M. Trezzi, N. Chiappini, V. Falqui, F. Londrino
• Journal: Journal of Nephrology
• Published: 2015;28(2):187-91
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Pemetrexed (Alimta(®)) (PEM) is an antifolate antineoplastic agent effective in several tumor types, such as non-small-cell lung cancer (NSCLC) and mesothelioma, among others. It is almost exclusively excreted by the kidney and an eGFR lower 45 mL/min is a contraindication for its use: above this level PEM administration is considered safe and dose adjustment is not required. Although there are some reported cases of PEM-induced renal injury, its incidence and the negative effects on patients' outcome has not been systematically evaluated.

Methods: We report a retrospective evaluation on the incidence of PEM-induced renal injury in patients affected by NSCLC. Between June 2010 and March 2012 a total of 38 NSCLC patients were treated at our hospital. In 29 of them other possible cause of renal injury were excluded and thus they were eligible to be analysed.

Results: Although by protocol all of them had eGFR >45 mL/min at baseline, six patients (average eGFR 56.2 ± 11.5 mL/min/1.73 m(2)) developed AKI (21 %). In these six patients PEM-induced myelosuppression was more severe and hospitalization was longer. Kidney function completely recovered in four patients whereas in the other two deterioration of renal function was irreversible. The number of patients with baseline eGFR <60 mL/min/1.73 m(2) was higher (4/6) in the group that developed AKI as compared to those who did not (6/23) (p < 0.05).

Conclusions: There is no clear cut eGFR above which PEM may be used without potential risks of renal toxicity. If PEM has to be used, all the coexisting risk factors for AKI should be possibly corrected.

In plain English

This retrospective study from an oncology unit in northern Italy examined kidney damage in non-small cell lung cancer patients given the cancer drug pemetrexed. It did not study asbestos exposure or mesothelioma patients. Of 38 patients who started pemetrexed between June 2010 and March 2012, 29 were analysed after others with possible causes of kidney injury were excluded. All had an estimated kidney filtration rate (eGFR) above 45 mL/min. Six of the 29 (21%) developed acute kidney injury, defined as serum creatinine rising above twice its baseline. Two months after pemetrexed was stopped, kidney function had fully recovered in four of them. The other two recovered only partly at six months, and one needed dialysis. Patients with acute kidney injury had more severe anemia and more often needed erythropoietin and filgrastim. Mildly reduced baseline kidney function (eGFR between 45 and 60) was more frequent in the injury group. The authors concluded that their data do not support assuming pemetrexed is safe whenever eGFR exceeds 45 mL/min. They noted that other concurrent conditions might have contributed.

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: retrospective single-centre evaluation of the incidence of pemetrexed-induced acute kidney injury
• Who was studied: 38 patients with non-small cell lung cancer who began second-line pemetrexed therapy between June 2010 and March 2012 at a hospital in northern Italy (authors' affiliation: St. Andrea Hospital, La Spezia). 9 were excluded for other possible causes of kidney injury, leaving 29 analysed (23 male, 6 female).
• Exposure: The chemotherapy drug pemetrexed, given alone (8 patients) or with other anticancer drugs such as cisplatin or carboplatin (21 patients). This is not an asbestos exposure.
• Main results:
  • Acute kidney injury occurred in 6 of the 29 analysed patients (21%).
  • Among the 6 patients with acute kidney injury, kidney function completely recovered in 4 two months after pemetrexed was discontinued. The other 2 had severe chronic deterioration with only partial recovery at 6 months.
  • One of the two patients with lasting damage required dialysis. That patient's kidney biopsy showed normal glomeruli with damage to the proximal tubular cells.
  • Baseline eGFR between 45 and 60 (stage 3A chronic kidney disease) was more frequent in patients who developed acute kidney injury: 4 of 6 versus 4 of 23 without it, p less than 0.05. The abstract and Table 2 instead give 6 of 23 for the group without injury.
  • Anemia was more severe in patients with acute kidney injury: hemoglobin 9.1 ± 1.3 versus 11.2 ± 1.5 g/dL in those without, p less than 0.001. Erythropoietin was needed by 5 of 6 (83%) versus 4 of 23 (17%), p less than 0.01.
  • Neutropenia requiring filgrastim occurred in 5 of 6 patients (83%) with acute kidney injury and 5 of 23 (21.7%) without, p less than 0.03.
  • Average cumulative pemetrexed dose was higher in the group without kidney injury: 6,550 ± 1,821 mg (8 ± 2 cycles) versus 3,491 ± 2,108 mg (3.8 ± 2.1 cycles) in the injury group, p = 0.0014. The authors found no clear cumulative dose–effect relationship.
• The authors' conclusion: The authors concluded that their data do not support the assumption that pemetrexed can be safely given when eGFR is above 45 mL/min, and that the incidence of acute kidney injury was higher than previously reported.
• Limitations the authors state:
  • The authors could not exclude that the kidney damage reflected pemetrexed toxicity amplified by other concurrent conditions.
  • Carboplatin may have contributed to kidney damage in the three injury cases who received it.
  • Bisphosphonates might partly be an alternative cause of the acute kidney injury.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

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

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• Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21, -200c, and -423 — M. Pavkovic, C. Robinson-Cohen, et al. (2016)
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