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

Zattera, Tito; Lotti, Francesco; Trezzi, Matteo; Palumbo, Roberto; Granata, Antonio; Tatangelo, Paola; Corbani, Valentina; Falqui, Valeria; Chiappini, Nadia; Mathiasen, Lisa; Cavallini, Marco; Rolla, Davide

doi:10.15171/jnp.2017.07

Cited by 17 publications

(11 citation statements)

References 15 publications

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“… 42 Pemetrexed is an antifolate antineoplastic agent that can be used alone or in combination with other antineoplastic drugs such as cisplatin. 43 , 44 As pemetrexed causes renal tubular toxicity, the association rule for combined use of cisplatin and pemetrexed suggested a risk of RI. 45 This indicates that co-administration of cisplatin and furosemide, loxoprofen, or pemetrexed may increase the risk of RI.…”

Section: Discussionmentioning

confidence: 99%

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database

et al. 2018

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Objectives:Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database.Methods:We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor.Results:In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5–3.0), 0.6 (0.5–0.7), 0.8 (0.7–1.0), and 1.3 (0.8–2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower–upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0–8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were <1. In the association rule mining, the score of lift for patients who were treated with cisplatin and co-administered furosemide, loxoprofen, or pemetrexed was high. Similarly, the scores for patients with hypertension or diabetes mellitus were high.Conclusion:Our findings suggest a potential risk of renal impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient’s background prior to treatment.

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Section: Discussionmentioning

confidence: 99%

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database

et al. 2018

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“…The significant difference in type of chemotherapy regimen (combination of cisplatin with pemetrexed, etoposide, gemcitabine or vinorelbine) could distort the observed nephrotoxicity. Since pemetrexed has been associated with nephrotoxicity the most (1%‐5% incidence of nephrotoxicity), a subgroup analysis was carried out on patients receiving a cisplatin/pemetrexed chemotherapy regimen (127/230 patients). There were no significant differences in renal function after repeated infusion of cisplatin in patients receiving a cisplatin/pemetrexed chemotherapy regimen between the rapid infusion cohort compared to the regular infusion cohort (eGFR 86.8 mL/min [83.6‐102.0] vs 87.9 [69.0‐96.7]; P = 0.764).…”

Section: Resultsmentioning

confidence: 99%

“…The risk of nephrotoxicity during treatment with pemetrexed is reported as 1%-5%, although data on this subject are mostly derived from case reports and relatively small studies. [25][26][27][28][29][30][31] Therefore, a subgroup analysis on patients receiving a cisplatin/ pemetrexed chemotherapy regimen was carried out. No significant differences in renal function or on the incidence of nephrotoxicity were found (Appendix S1).…”

Section: Discussionmentioning

confidence: 99%

“…Of all the antineoplastic agents that are combined with cisplatin in patients with lung carcinoma, pemetrexed has been associated with nephrotoxicity the most. The risk of nephrotoxicity during treatment with pemetrexed is reported as 1%‐5%, although data on this subject are mostly derived from case reports and relatively small studies . Therefore, a subgroup analysis on patients receiving a cisplatin/pemetrexed chemotherapy regimen was carried out.…”

Section: Discussionmentioning

confidence: 99%

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The effect of rapid infusion of cisplatin on nephrotoxicity in patients with lung carcinoma

et al. 2018

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Summary What is known and objective The use of cisplatin in the treatment of lung carcinoma is limited by nephrotoxicity. The aim of this study was to determine whether the incidence of nephrotoxicity in patients with lung carcinoma is affected by the infusion rate of cisplatin (rapid infusion of cisplatin in 1 hour compared to regular infusion in 3 hours). Methods This observational, retrospective study was performed on patients diagnosed with non‐small‐cell lung carcinoma (NSCLC), small‐cell lung carcinoma (SCLC) or mesothelioma receiving a cisplatin‐containing chemotherapy regimen. Patients were divided into two cohorts (infusion of cisplatin in 1 hour vs 3 hours) based on the starting date of the chemotherapy regimen. The primary objectives were the difference in renal function after three cycles of chemotherapy and the incidence of nephrotoxicity. To assess nephrotoxicity, both the incidence of acute kidney injury (AKI) grade 1 and the maximum decrease in estimated glomerular filtration rate (eGFR) were determined. Results A total of 230 lung carcinoma patients with a cisplatin‐containing chemotherapy regimen were included. Baseline characteristics were similar for the rapid and regular infusion cohorts, except for type of lung carcinoma, chemotherapy regimen and prevalence of hypertension. There was no significant difference in renal function between rapid infusion of cisplatin and regular infusion of cisplatin (eGFR 86.1 mL/min [71.0‐96.3] vs 87.9 mL/min [71.6‐97.3]; P = 0.938). The incidence of AKI grade 1 was not significantly different between rapid and regular infusion of cisplatin (29.3% vs 29.8%; P = 0.932). The maximum decrease in eGFR was 14.8 mL/min in the rapid infusion cohort and 17.7 mL/min in the regular infusion cohort (P = 0.364). What is new and conclusion The incidence of nephrotoxicity after repeated infusion of cisplatin was not affected by the infusion rate of cisplatin. Therefore, a 1‐hour infusion of cisplatin is a safe and feasible method, which may potentially shorten duration of hospital admittance and enable treating patients in the outpatient setting.

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“…Renal biopsy was performed on a small number of patients. [7][8][9][10] Figure 1: Structure of pemetrexed. 2…”

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confidence: 99%

A retrospective study on pemetrexed induced nephrotoxicity in non-small cell lung carcinoma patients

Reddy¹,

Punukula²,

Bhavya³

et al. 2021

Int J Basic Clin Pharmacol

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Background: Pemetrexed (PEM) is a new-generation multitargeted antifolate agent that has been shown to have broad-spectrum efficacy in a variety of human cancers, including NSCLC and mesothelioma. Dose-limiting hematologic toxicities are among the most serious side effects. PEM nephrotoxicity is well-known, but its occurrence is thought to be rare. Aim was to determine nephrotoxicity induced due to pemetrexed in non-small cell lung cancer patients.Methods: In patients with the NSCLC, we record a retrospective review on PEM- induced renal toxicity. A total of 327 NSCLC patients were treated in our hospital between 2012 and 2019. Of these, 134 patients were diagnosed with 2 or more chemotherapy cycles. 60 of these patients have been diagnosed with combination of antineoplastic drugs based on pemetrexed and platinum. Others were removed from the study and were also required to be tested for other potential causes of renal injury.Results: Suitable statistical tools were used and data was analysed which showed that repeated chemo cycles of pemetrexed leads to the reversible acute kidney injury. With the results from our study we can understand the severity of nephrotoxicity induced with pemetrexed in patients with non-small cell lung cancer. Most of the patients were in the first and second stages of nephrotoxicity and most of them were male. Majority of the patients were also above 40 years of age and also endured more than 4 chemo cycles.Conclusions: It shows that PEM allows longer survival, but acute or chronic kidney failure is the price for this achievement. In conclusion, renal toxicity should be controlled routinely in patients treated with pemetrexed. Before each cycle of pemetrexed, creatinine clearance should be measured. Patients need to be well hydrated during treatment. The patient should also be tested for concomitant medications, and any nephrotoxic symptoms should be reviewed and those drugs removed.

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

Cited by 17 publications

References 15 publications

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database

The effect of rapid infusion of cisplatin on nephrotoxicity in patients with lung carcinoma

A retrospective study on pemetrexed induced nephrotoxicity in non-small cell lung carcinoma patients

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