Efectos del precondicionamiento isquémico remoto sobre la nefropatía asociada a contraste en pacientes diabéticosrelación con el estrés oxidativo y el estado inflamatorio

Resumen

INTRODUCTION: The use of intravascular contrast media can lead to secondary acute kidney injury called contrast-associated nephropathy (CN). Diabetes mellitus (DM) is a key predisposing factor for its development. Several experimental studies have shown that oxidative stress and inflammatory activation play a key role in the pathogenesis of CN, and therefore the activation of renal antioxidant and anti-inflammatory systems is essential for its prevention. One of these protective systems is constituted by the enzyme heme oxygenase-1 (HO-1). Several experimental studies have shown an increase in the levels of this enzyme after remote ischaemic preconditioning (RIP) manoeuvres. However, there is some controversy as to whether the protective effect of RIP is partially abolished in the diabetic patient. For this reason, we wanted to focus this study on this population. HYPOTHESIS: RIP exerts preventive effects on contrast-associated nephropathy, by activating anti-inflammatory and antioxidant mechanisms, in diabetic patients undergoing preferential coronary interventionism. OBJECTIVES: The specific objectives of this Doctoral Thesis work are: OBJECTIVE 1: To assess the impact on the total incidence of CN of a RIP manoeuvre in a population of diabetic patients undergoing coronary arteriography. OBJECTIVE 2: To analyse the influence of the RIP manoeuvre on the incidence of CN, in relation to the risk factors associated with the development of this pathology, in a population of diabetic patients. OBJECTIVE 3: To evaluate the effect of a RIP manoeuvre on the temporal evolution of the inflammatory state by determining changes in white blood count, C-reactive protein and plasma ferritin level, and their relationship with the development of CN. OBJECTIVE 4: To determine the changes in the levels of the antioxidant defence system haemoxygenase-1 (HO-1) before and after the performance of a RIP manoeuvre and their relationship with the development of CN. OBJECTIVE 5: To evaluate the effect of RIP on ICU stay, mortality, readmission, situation and need for dialysis in diabetic patients undergoing preferential coronary intervention after 6 weeks. METHODOLOGY: Single-centre clinical trial, of parallel groups, with random distribution. Diabetic patients who were going to undergo preferential coronary intervention were included. After information and obtaining informed consent, they were randomised with sealed envelopes, in blocks, to two groups: to receive RIP manoeuvre and not to receive RIP. RESULTS: Our sample presented a homogeneous distribution with respect to their baseline demographic characteristics, risk factors and analytical variables, between RIP/non-RIP groups. The total incidence of CN we found was 32%, with no difference in incidence between the RIP and non-RIP groups. The incidence of CN was similar in the analysis by subgroups according to higher risk factors such as renal function prior to catheterisation, haemodynamic situation prior to and during catheterisation, volume of contrast used during the procedure in relation to glomerular filtration rate, and chronic glycaemic control. The time course of inflammatory and antioxidant status was not related to an increased incidence of developing CN and was not significantly modified by the RIP manoeuvre. Receiving or not the RIP manoeuvre did not influence the development of adverse events in the time frame analysed. CONCLUSIONS: Based on our results we can describe the lack of efficacy of the RIP manoeuvre, in our diabetic patients, in terms of protecting them from developing CN, the independence, of such a manoeuvre, on inflammatory, antioxidant behaviour and on the occurrence of adverse events.