Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy

• Published in: International journal of molecular sciences 2021-01, Vol.22 (3), p.1239
• Main Authors: Zaballos, Matilde, Power, Mercedes, Canal-Alonso, María Iluminada, González-Nicolás, María Ángeles, Vasquez-Jimenez, Wenceslao, Lozano-Lominchar, Pablo, Cabrerizo-Torrente, Pilar, Palencia-García, Natividad, Gago-Quiroga, Susana, Ginel-Feito, María Dolores, Jiménez, Consuelo, Lázaro, Alberto, González-Bayón, Luis
• Format: Article
• Language: English
• Subjects: Abdomen; Abdominal surgery; Adult; Aged; Antibiotics; Antineoplastic Agents - therapeutic use; Cancer therapies; Chemotherapy; cilastatin; Cilastatin - pharmacology; Cilastatin - therapeutic use; Cisplatin; Cisplatin - adverse effects; Combined Modality Therapy - methods; Creatinine; Creatinine - blood; Drug dosages; Female; Fever; Fluid management; Gastric cancer; Hemodynamics; HIPEC; Humans; Hydration; Hyperthermia; Hyperthermic Intraperitoneal Chemotherapy - adverse effects; Hyperthermic Intraperitoneal Chemotherapy - methods; Imipenem; Imipenem - pharmacology; Imipenem - therapeutic use; imipenem/cilastatin; Kidney - drug effects; Kidneys; Male; Mesothelioma; Middle Aged; nephroprotection; nephrotoxicity; Ovaries; Patients; Perfusion; Peritoneal Neoplasms - complications; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - mortality; Peritoneum; Prophylaxis; Prospective Studies; Renal function; Renal Insufficiency - complications; Renal Insufficiency - etiology; Renal Insufficiency - prevention & control; Retrospective Studies; Risk analysis; Risk factors; Surgery
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22031239

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control ( = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group ( = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.