HIPEC-Induced Acute Kidney Injury: A Retrospective Clinical Study and Preclinical Model

Abstract

Background Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) is the treatment of choice for selected patients with peritoneal malignancies. HIPEC is accompanied by moderate-to-high patient morbidity, including acute kidney injury. The significance of nephrotoxic agents such as cisplatin versus hyperthermia in HIPEC-induced nephrotoxicity has not been defined yet. Patients and Methods A total of 153 patients treated with HIPEC were divided into groups with (AKI+) and without (AKI−) kidney injury. Laboratory parameters and data concerning patient demographics, underlying disease, surgery, complications, and HIPEC were gathered to evaluate risk factors for HIPEC-induced AKI. A preclinical mouse model was applied to assess the significance of cisplatin and hyperthermia in HIPEC-induced AKI, as well as protective effects of the cytoprotective agent amifostine. Results AKI occurred in 31.8% of patients undergoing HIPEC. Treatment with cisplatin-containing HIPEC regimens represented a major risk factor for HIPEC-related AKI (p < 0.001). Besides, angiotensin receptor blockers and increased preoperative creatinine and urea levels were independent risk factors for AKI after HIPEC. In a preclinical mouse model, intraperitoneal perfusion with cisplatin induced AKI, whereas hyperthermia alone, or in combination with cisplatin, did not induce or enhance renal injury. Amifostine failed to confer nephroprotective effects in a miniaturized HIPEC model. Conclusions AKI is a frequent complication after HIPEC. The risk of renal injury is particularly high in patients treated with cisplatin-containing HIPEC regimens. Hyperthermic perfusion of the abdomen by itself does not seem to induce or aggravate HIPEC-induced renal injury.

Acute kidney injury after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer

“…As one of the serious complications in cancer patients, AKI has been proven to be associated with increased all-cause mortality and received great attention in clinical settings in recent years ( 20 , 21 ). Previous studies showed that the incidence of AKI after CRS plus HIPEC ranged from 1 to 48% ( 9 ). This vast variability might be related to the different ethnicities of the study population, and different chemotherapy protocols and doses applied in the treatment, besides, lacking consensus criteria of AKI might be another important reason for such a large variability of the incidence of AKI among those patients ( 22 ).…”

“…However, there are also data indicating that the application of CRS plus HIPEC has some non-eligible complications, and most causes of systemic toxicity of it are related to renal toxicity and bone marrow failure ( 7 , 8 ). The occurrence of acute kidney injury (AKI) in patients undergoing CRS plus HIPEC was also reported, and the incidence of it varied widely between 1% and 48%, the reason for the great variability in the prevalence of AKI might be related to different study populations, different regimens and doses for chemotherapy, besides these, the application of different definitions of AKI was also an important reason for that wide range of the AKI occurrence ( 9 ). Meanwhile, some associated risk factors for the occurrence of AKI like increased age, obesity, intraoperative blood loss, baseline renal dysfunction, preoperative hypoalbuminemia, and use of angiotensin-II receptor antagonists were identified among those patients ( 10 – 12 ).…”

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

“…Harnessing the excess RONS in renal system is an effective strategy for AKI treatment. Some small molecule antioxidants such as N-acetylcysteine (NAC), amifostine (AMF), and l -carnitine have been adopted in the adjuvant treatment of AKI [ [137] , [138] , [139] , [140] ]. However, these drugs have failed to become primary treatment for AKI owing to the low kidney targeting.…”

Temperature management during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

“…Additionally, the incremental activity of the sympathetic nervous system causes vasoconstriction of the splanchnic and renal circulation which combine with hypovolemia during HIPEC increases the risk of acute kidney injury. Interestingly, preclinical data suggest that hyperthermic perfusion itself does not aggravate HIPEC-induced acute renal failure and indeed is mostly the cytotoxic side effects of chemotherapy that causes the acute kidney injury in patients undergoing CRS-HIPEC ( 64 ).…”