P0622FIGHTING AGAINST PROXIMAL AND DISTAL TUBULAR DAMAGE BY REDUCING INFLAMMATORY BURDEN AFTER CARDIAC SURGERY

Abstract

Abstract Background and Aims Going on cardiopulmonary bypass (CPB) during cardiac surgery causes systemic inflammatory response syndrome. In different studies Pentoxifylline and Calcitriol have shown inhibitory effects on pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) accompanying with production of free oxygen radicals in the ischemic reperfusion injury. On the other hand, they have positive effects on reducing oxidative stress. To investigate the effects of these drugs on reducing tubular injury after CABG surgery, by their anti-inflammatory properties we compared pre- and postoperative levels of urinary NGAL (as a proximal tubular damage marker), KIM-1 level (as a distal tubular damage marker), serum level of Malondialdehyde (MDA) (as an oxidative stress marker) and serum inflammatory markers such as IL-6, IL-8, and TNF levels in two groups of patients undergoing CABG, those who received Pentoxifylline and Calcitriol before surgery and those who didn't Method After signing an informed consent, 150 consecutive adult patients undergoing elective on-pump CABG were enrolled in a randomized control trial. Patients with collagen-vascular disease or having a history of treatment with immunosuppressive agents, corticosteroids (> 3 days), Methylxantines, Diltiazem or sodium Nitroprusside and patients with a history of angiography in the past 7 days or hemorrhagic diathesis and coagulopathy, uncontrolled diabetes mellitus, sepsis, renal failure (sCr > 2 mg/dl), hepatic failure (AST or ALT > 40 U/L) or urinary tract infection were excluded. All patients received the same anesthetic regimen and routine CPB management. The patients were randomly assigned to one of two groups: PTX was administered as an oral 400 mg tab every 12hours plus IV Calcitriol (0.01 mcg/kg) daily starting from 3 days before surgery. In the control group placebo tab and IV injection of normal saline were prescribed in the same direction. Results Results demonstrated that after three days prophylactic use of oral pentoxifylline plus IV Calcitriol there is improvement in selected checked inflammatory markers in the intervention group. Moreover Pentoxifylline+ Calcitriol showed beneficial effects by controlling the oxidative stress burden and reducing the mean serum MDA level in the patients undergoing CABG who are at risk of developing AKI as a post surgery complication. Probably by reducing inflammation and oxidative stress combination of these two drugs before CABG could decrease proximal and distal tubular damage which presented with significantly lower levels of uNGAL and KIM-1, as markers of tubular injury, in the intervention group. Conclusion Combination of Pentoxifylline and Calcitriol showed a promising prophylactic role in patients undergoing CABG with anti-inflammatory, anti-oxidant properties. This study provided scope of add-on drug therapy for better prognosis in post CABG population, involving risk of endothelial dysfunction and renal tubular damage due to inflammatory milieu and renders support to future prospective clinical studies to demonstrate net control of inflammation and oxidative stress after cardiac surgery.