Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study

Abstract

Background Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. Patients and Methods We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. Results Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. Conclusions The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies.

Hypoxia-Driven Responses in Chronic Kidney Disease

“…Treatment of db/db mice with GKT136901, a NOX1/NOX4 inhibitor, blocked renal NOX4dependent fibrotic signaling after exposure to high glucose [198]. Of note, H 2 S donors, such as sodium thiosulfate, maintain redox homeostasis by ROS scavenging and modifying cysteine residues on key signaling molecules, which exerts renal protection [199,200]. Vitamin E reduced cardiovascular disease and myocardial infarction events in hemodialysis patients [201].…”

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

“…In fact, previously published patient cohorts do not consistently provide information on the extent of parietal peritonectomy or CDDP perfusate concentration, which precludes appropriate comparison. However, we do not intend to rule out that the absence of routinely applied nephroprotective agents 38 , 39 or goal-directed fluid management strategies 34 may have additionally contributed to a rather high incidence of CDDP HIPEC-induced AKI in our patient cohort.…”

Impact of Sodium Thiosulfate on Prevention of Nephrotoxicities in HIPEC: An Ancillary Evaluation of Cisplatin-Induced Toxicities in Ovarian Cancer

“…Although some trials have shown the nephroprotective effect of ST, they have been largely retrospective or observational in design. 23 , 24 The OVHIPEC-1 study demonstrated improved survival outcomes in advanced stage ovarian cancer patients and included ST prophylaxis in the protocol, and no renal AEs were reported. 1 Baseline creatinine was similar between the ST and nST groups.…”