Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma

Our plain-English summary of Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma, by T. Hod, K.J. Freedberg, S.S. Motwani, et al (The Journal of Thoracic and Cardiovascular Surgery, 2021).

The study

• Authors: T. Hod, K.J. Freedberg, S.S. Motwani, M. Chen, G. Frendl, D.E. Leaf, S. Gupta, S.S. Mothi, W.G. Richards, R. Bueno, S.S. Waikar
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2021;161(4):1510-1518
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin has been used successfully to treat malignant pleural mesothelioma, a highly aggressive malignancy that is rapidly fatal in most cases. We hypothesized that the combination of ischemic injury with nephrotoxic injury from cisplatin would result in high rates of acute kidney injury.

Methods: We conducted an observational study in 503 patients to study the risks and outcomes of acute kidney injury after surgical resection of malignant pleural mesothelioma. Eligible subjects underwent extrapleural pneumonectomy or pleurectomy/decortication with or without hyperthermic intraoperative chemotherapy. Acute kidney injury was defined as an increase in creatinine of 26.5 μmol/L or greater within 48 hours of surgery or a 50% or greater increase over 7 days.

Results: Acute kidney injury developed in 243 patients (48.3%). Severe acute kidney injury requiring renal replacement therapy developed in 16 patients (3.2%). Major significant predictors for acute kidney injury included male sex (odds ratio, 2.98; P < .001), intraoperative cisplatin administration (odds ratio, 3.12; P < .001), previous cisplatin exposure (odds ratio, 1.96; P = .02), hypertension (odds ratio, 1.57; P = .02), and longer surgical time (odds ratio, 1.15 per hour; P = .02). Compared with patients without acute kidney injury, those with severe acute kidney injury had longer length of stay (26 vs 13 days) and a 2.71-fold increased risk of death in multivariable-adjusted models.

Conclusions: Acute kidney injury is common after cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin and is associated with poor long-term outcomes. Strategies to prevent postoperative acute kidney injury are needed to improve multimodal treatment of malignant pleural mesothelioma.

Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In plain English

The authors reviewed records of 503 patients operated on for malignant pleural mesothelioma at Brigham and Women's Hospital, Boston, in 2006 to 2015. Patients had extrapleural pneumonectomy or pleurectomy/decortication; 412 also received heated cisplatin chemotherapy in the chest during surgery. Acute kidney injury (a sudden rise in blood creatinine) developed in 243 (48.3%), mostly the mildest stage. Sixteen (3.2%) needed renal replacement therapy, such as dialysis; all had received cisplatin. In adjusted analyses, male sex, cisplatin during surgery, earlier cisplatin treatment, high blood pressure, longer surgery and higher baseline estimated kidney filtration (eGFR) were linked to injury. The authors thought the eGFR link likely reflected low muscle mass, not better kidney function. Patients with the most severe stage stayed a median of 26 days, against 13 without injury. They also had a 2.71-fold higher adjusted risk of death (95% confidence interval 1.65 to 4.45). Prior asbestos exposure was similar in patients with and without kidney injury. The authors concluded that kidney injury is common after this treatment and associated with poor long-term outcomes. They noted the study came from a single center.

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: Observational cohort study: a retrospective review of a prospectively assembled cohort of surgical patients
• Who was studied: 503 patients who had surgical resection for malignant pleural mesothelioma at Brigham and Women's Hospital, Boston, between 2006 and 2015; mean age 67.1 years, mostly male and white
• Exposure: Cytoreductive surgery (extrapleural pneumonectomy or pleurectomy/decortication) with or without hyperthermic intraoperative chemotherapy. 412 patients (81.9%) received cisplatin, either alone (170) or with gemcitabine (242), at 175 to 225 mg/m2 cisplatin. The exposure studied was this medical treatment, not asbestos.
• Main results:
  • Acute kidney injury developed in 243 of the 503 patients (48.3%).
  • Most kidney injury was the mildest stage (KDIGO stage 1).
  • 16 patients (3.2%) required renal replacement therapy. All of them had received cisplatin, and most of them still produced urine.
  • Kidney injury was more common in men than in women: 54.6% vs 28.0%.
  • Kidney injury occurred in 53.6% of patients who received intraoperative cisplatin (with or without gemcitabine), compared with 24.2% of those who received no cisplatin.
  • In the stepwise multivariable model, male sex had an odds ratio for kidney injury of 2.98 (95% CI 1.85-4.80).
  • In the stepwise multivariable model, intraoperative cisplatin had an odds ratio for kidney injury of 3.12 (95% CI 1.77-5.5).
  • In the stepwise multivariable model, previous cisplatin exposure had an odds ratio for kidney injury of 1.96 (95% CI 1.17-3.27).
  • In the stepwise multivariable model, hypertension had an odds ratio for kidney injury of 1.57 (95% CI 1.06-2.32).
  • In the stepwise multivariable model, total surgical time had an odds ratio for kidney injury of 1.15 per hour (95% CI 1.02-1.28).
  • Higher baseline estimated glomerular filtration rate (eGFR) was associated with a higher risk of kidney injury, which the authors called surprising.
  • The authors attributed the eGFR association likely to confounding from muscle mass: lower muscle mass and cachexia lower creatinine and so raise eGFR for a given level of kidney function.
  • Median hospital stay was 13 days without kidney injury, and 14, 15 and 26 days with kidney injury stages 1, 2 and 3, respectively.
  • Death rates per 100 person-years were 32.9 without kidney injury, and 41.4, 51.6 and 106 with stages 1, 2 and 3, respectively.
  • In multivariable-adjusted models, compared with no kidney injury, the risk of death was 1.15 (95% CI 0.90-1.47) for stage 1, 1.25 (95% CI 0.79-1.98) for stage 2, and 2.71-fold (95% CI 1.65-4.45) for stage 3.
  • Use of hyperthermic intraoperative chemotherapy with cisplatin was associated with a greater risk of kidney injury but a lower risk of death.
  • Prior asbestos exposure was recorded in 170 of 260 patients (65.4%) without kidney injury and 169 of 243 (69.5%) with kidney injury (P = .39).
• The authors' conclusion: The authors concluded that acute kidney injury is common after cytoreductive surgery with intrathoracic cisplatin for malignant pleural mesothelioma and is associated with poor long-term outcomes.
• Limitations the authors state:
  • Generalizability is limited because the study came from a single center performing a technically demanding procedure.
  • The data were not collected specifically to study kidney injury risk factors or to compare survival across treatments, so some variables (for example, low blood pressure during surgery) were not available.
  • All patients receiving intrathoracic cisplatin were given protective thiosulfate and amifostine, so the effect of these drugs on kidney injury could not be compared.
  • The study was not designed to study treatment effects.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, Cisplatin, Chemotherapy, Pleural Mesothelioma, Surgical Resection, Extrapleural Pneumonectomy (EPP), Pleurectomy/Decortication (P/D), Odds Ratio.

Related studies

• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Multicystic mesothelioma: Operative and long-term outcomes with cytoreductive surgery and hyperthermic intra peritoneal chemotherapy — E. Nizri, D. Baratti, et al. (2018)
• Commentary: Cisplatin-induced nephrotoxicity following cytoreductive surgery and heated intraoperative chemotherapy for malignant pleural mesothelioma — S.S. Groth, R.T. Ripley (2021)
• 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)
• Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma — S. van Ruth, O. van Tellingen, et al. (2003)
• Commentary: Acute kidney injury after intrapleural cisplatin: Minimizing collateral damage — M.I. Ebright (2021)

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