Renal dysfunction and protection in cardiovascular surgery

Sammanfattning: Purpose: This thesis is focused on studies of postoperative renal dysfunction (PRD), and on renal effects and possible prophylactic potentials of three vasoactive substances, calcitonin gene-related peptide (CGRP), atrial natriuretic peptide (ANP), and the calcium channel antagonist diltiazem. Methods: In paper I the medical records of 1 030 consecutive cardiothoracic surgery patients were evaluated and glomerular filtration calculated from serum creatinine levels. In paper II experimental renal ischemia was induced in normal rats. Treatment with CGRP 10 or 25 pmol/kg/min was evaluated by comparing serum urea elevations with controls. In paper III ANP 7.5 pmol/kg/min was infused postoperatively in vascular surgery patients and the renal and hemodynamic effects studied. In paper IV the renal and hemodynamic effects of ANP infusion 7.5 pmol/kg/min were studied immediately postoperatively in cardiac surgery patients. In paper V the renal and hemodynamic effects of diltiazem infusion was studied in postoperative vascular surgery patients. In paper VI diltiazem treatment for 24 h in connection with cardiac surgery was compared to placebo, in patients with a preexisting moderate renal dysfunction. Iohexol clearance was measured before surgery and 5 days and 3 weeks postoperatively. Results and Implications: The incidence of postoperative renal dysfunction (PRD) after open heart surgery was 11 %. In PRD patients, the mortality rate was 12.4 %, compared with 0.4 % in Non-PRD patients. After experimental renal ischemia, CGRP had a protective effect on renal function. The protective effect was dose related as the higher CGRP dose resulted in systemic hypotension. ANP infusion improved glomerular filtration rate, urine flow, and sodium excretion in humans in the postoperative setting, in vascular as well as cardiac surgery patients. There were no hemodynamic side effects of diltiazem treatment (bolus 0.25 - 0.28 mg/kg, followed by infusion of 1.0 _ 1.7 [my]g/kg/min). It was shown that diltiazem, in patients with preexisting renal impairment, protected and even improved their renal function after cardiac surgery. In future studies it would be of interest to further explore the renal outcome after major surgery, trauma and shock, using as protective agents both CGRP and ANP, not only separately but also in combinations including diltiazem.