Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury

Our plain-English summary of Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury, by L.F. Liesenfeld, E. Quiring, M. Al-Saeedi, et al (Annals of Surgical Oncology, 2023).

The study

• Authors: L.F. Liesenfeld, E. Quiring, M. Al-Saeedi, C. Nusshag, M.W. Büchler, M. Schneider
• Journal: Annals of Surgical Oncology
• Published: 2023;30(5):2646-2656
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated.

Patients And Methods: Data from 63 patients treated with a CDDP-containing HIPEC regimen were retrospectively analyzed concerning demographics, underlying disease, surgery, and HIPEC details to evaluate risk factors of AKI. A preclinical rat perfusion model was applied to assess the influence of temperature, concentration, perfusate volume, perfusion flow rate, and extent of peritonectomy on drug absorption upon intraperitoneal CDDP perfusion.

Results: AKI occurred in 66.1% of patients undergoing CDDP-containing HIPEC, with total intraoperative fluid influx being a negative and the extent of parietal peritonectomy being a positive independent predictor of postoperative AKI. In a preclinical model, bilateral anterior parietal peritonectomy significantly increased systemic CDDP absorption by 1.6 to 2-fold. CDDP plasma levels in animals were significantly higher after both perfusion with increased CDDP perfusate concentrations and bilateral anterior parietal peritonectomy.

Conclusion: CDDP-containing HIPEC is associated with relevant morbidity owing to its systemic toxicity. Extent of parietal peritonectomy is an independent predictor of AKI. CDDP dose reduction should be considered in case of extensive parietal peritonectomy. Cytostatic drug concentrations in HIPEC perfusate should be paid more attention to than total dose per body surface area. Further clinical studies are needed to confirm the presented preclinical findings.

© 2022. The Author(s).

In plain English

This study examined kidney damage after surgery plus heated abdominal cisplatin chemotherapy (HIPEC) at Heidelberg University Hospital, Germany. It did not study asbestos exposure. The authors reviewed 63 patients treated 2007 to 2020. Of the 56 analyzed for risk factors, 17 had mesothelioma and the rest had gastric or ovarian cancer that had spread in the abdomen. Acute kidney injury occurred in 37 of 56 (66.1%). Five needed temporary dialysis and two needed permanent kidney replacement therapy. Underlying disease did not differ significantly by injury status. In a statistical model, each added point on a 0-to-7 score of how much abdominal wall lining was removed (parietal peritonectomy) was linked to higher odds of injury (odds ratio 1.518, 95% CI 1.129 to 2.040). More fluid given during surgery, measured per kg of body weight, was linked to lower odds (odds ratio 0.958, 95% CI 0.934 to 0.982). In rats, removing part of the lining increased cisplatin uptake into the blood 1.6 to 2-fold. The authors concluded that peritonectomy extent independently predicts kidney injury. They also concluded that a lower cisplatin dose should be considered when peritonectomy is extensive. They noted the rat model may not reflect patients.

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 clinical study of patient records, combined with an animal (rat) perfusion experiment
• Who was studied: 63 patients (64 treatments) given cisplatin-containing HIPEC at Heidelberg University Hospital, Germany, from 2007 to 2020. 56 were included in the risk-factor analysis: 17 with mesothelioma, 24 with peritoneal carcinomatosis from gastric cancer and 15 from ovarian cancer. Rats: 8 per experimental group.
• Exposure: Cisplatin (CDDP) given as heated intraperitoneal chemotherapy after cytoreductive surgery, alone or with doxorubicin or mitomycin C. Extent of parietal peritonectomy was scored from 0 to 7. No asbestos exposure was studied.
• Main results:
  • Acute kidney injury (KDIGO criteria) occurred in 37 of 56 patients (66.1%) treated with cisplatin-containing HIPEC.
  • Among the 37 patients with kidney injury, 20 had stage 3 injury. Five patients with stage 3 injury required temporary hemodialysis and two required permanent renal replacement therapy.
  • Demographics, underlying malignant disease (including mesothelioma) and HIPEC regimen did not differ significantly between patients with and without kidney injury.
  • In binary logistic regression, the Parietal Peritonectomy Score (0 to 7 points, 1 point per resected area) was a positive independent predictor of kidney injury (OR 1.518, 95% CI 1.129 to 2.040, p = 0.006). Intraoperative fluid influx (measured in ml per kg body weight) was a negative predictor (OR 0.958, 95% CI 0.934 to 0.982, p = 0.001).
  • In rats, bilateral anterior parietal peritonectomy significantly increased cisplatin absorption to 14.1%, 17.3% and 18.3% at 30, 60 and 90 minutes. The reference hyperthermia group absorbed 7.1%, 9.2% and 11.1%. This is a 1.6 to 2-fold increase.
  • In rats, doubling the cisplatin perfusate concentration increased absorption, but the difference was not statistically significant. Normothermia, reduced perfusate volume and reduced flow rate had no significant effect.
• The authors' conclusion: The authors concluded that the extent of peritonectomy is an independent predictor of kidney injury after cisplatin HIPEC. They argued for considering a cisplatin dose reduction in cases requiring extensive parietal peritonectomy. They stated that pharmacological and prospective clinical studies are required to prove this.
• Limitations the authors state:
  • Determining the extent of peritonectomy precisely from retrospective clinical data is difficult.
  • The HIPEC drug regimens used were heterogeneous.
  • Rats differ from humans: more of the perfusate sits in the tubing, and diffusion distances are shorter. The authors do not claim peritonectomy is as relevant in patients as in the rat model.
  • The absence of routine nephroprotective agents or goal-directed fluid management may have contributed to the high kidney injury rate.

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, HIPEC, Ovarian Cancer, Stomach Cancer, Peritoneal Mesothelioma, Bilateral.

Related studies

• Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review — D. Chen, Y. Ma, et al. (2025)
• Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma — T. Hod, K.J. Freedberg, et al. (2021)
• Commentary: Acute kidney injury after intrapleural cisplatin: Minimizing collateral damage — M.I. Ebright (2021)
• 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)
• 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)
• Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform — S.D. Forsythe, R.A. Erali, et al. (2023)

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