期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms22031239
关键词
cisplatin; imipenem; cilastatin; cilastatin; HIPEC; nephrotoxicity; nephroprotection
资金
- Spanish Ministry of Economy and Competitiveness Instituto de Salud Carlos III-Fondo de Investigacion en Salud (ISCIII-FIS) [PI11/01132, PI14/01195, PI17/00276]
- Fondo Europeo de Desarrollo Regional (FEDER) Funds from the European Commission, A way of making Europe
- ISCIII-Red Tematica de Investigacion Cooperativa en Salud (RETIC) [REDinREN/RD16/0009/0026]
- Comunidad de Madrid [S2017-BMD-3686 (CIFRA2-CM)]
- Fundacion Senefro [SENEFRO 18/01]
- Fundacion Mutua Madrilena
Preventive use of imipenem/cilastatin can reduce the nephrotoxicity of cisplatin in patients with peritoneal carcinomatosis, leading to lower creatinine values and shorter ICU and hospital stay in the postoperative period.
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 (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 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, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.
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