Abstract
Abstract Background and Aims Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin is increasingly used for the treatment of ovarian and peritoneal cancer. Acute kidney injury (AKI) is a frequent complication after cisplatin containing HIPEC therapy. The aim of this study was to compare the incidence and severity of AKI and renal survival after HIPEC compared to repeated cycles of conventional high-dose intraperitoneal cisplatin in patients with ovarian and malignant peritoneal cancer. Method We conducted a retrospective study that included patients with ovarian cancer that received repeated cycles of high-dose intraperitoneal cisplatin and patients with ovarian and primary malignant peritoneal cancer that received HIPEC with cisplatin in our center between August 2006 and September 2022. Demographic and perioperative data were compared between both groups. We compared the incidence of AKI defined as a rise in serum creatinine by ≥ 0.3 mg/dL within 48 hours (KDIGO criteria), the severity of AKI defined as stages I, II and III using the KDIGO staging, the rate of kidney function recovery and need for renal replacement therapy in both groups. We performed logistic regression analysis to identify independent risk factors for experiencing AKI and conducted survival analyses and multivariate Cox regression analyses to detect independent risk factors for patient survival. Results The study included 39 patients; 20 received 76 cycles of conventional intraperitoneal cisplatin, and 19 patients (13 with ovarian cancer and 6 with primary peritoneal cancer) received HIPEC. Patients who received HIPEC were older (63.4±20 years vs 56±8 years, p = 0.002) and received a lower dose of cisplatin both in absolute values (109.2±41.1 mg vs 159.2±15.2 mg, p<0.001) and adjusted by body surface area (63.4±19.9 mg/m2 vs 96.8±9.2 mg/m2, p<0.001). AKI was significantly more frequent in patients receiving HIPEC (42.1% vs 15.8%, p = 0.012), and was more severe after HIPEC with AKIN-I, AKIN-II and AKIN-III in 50% vs 83%, 12.5% vs 16.7% and 37.5% vs 0% respectively, p = 0.042. Recovery from AKI was more frequent in patients receiving conventional intraperitoneal cisplatin (100% vs 50%, p = 0.014) and 1 patient in the HIPEC group progressed to end stage kidney disease. In the multivariate logistic regression analysis, after adjusting for age, baseline serum creatinine and cisplatin dose, treatment with HIPEC compared to conventional high-dose intraperitoneal cisplatin remained a significant risk factor for developing AKI (OR 1550, CI 95% 19-128070). Conclusion Cisplatin-based HIPEC therapy is associated with an increased risk of severe AKI compared to conventional high-dose intraperitoneal cisplatin regimens, despite the use of prophylactic measures. Hyperthermic perfusion of the abdomen might be an important contributing factor in HIPEC-induced renal injury. To reduce the incidence of AKI and its associated morbidity after HIPEC, early implementation of preventive measures with adequate fluid management and closer monitoring of hemodynamic parameters and kidney function tests should be taken into consideration.
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