Rear, Roger; (2017) The effect of remote ischaemic preconditioning on contrast induced nephropathy in the clinical setting of coronary angiography and percutaneous coronary intervention. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Contrast Induced Nephropathy (CIN) is a common and serious iatrogenic complication resulting from the use of intravascular iodinated contrast media in routine investigations such as coronary angiography. Patients with impaired renal function are particularly at risk of CIN and a number of well recognised clinical and procedural risk factors exist which can be integrated into several risk scoring models. The principal pathophysiological mechanism for CIN consists of a renal ischaemia reperfusion injury (IRI) induced by the physico-chemical properties of contrast media in susceptible individuals. Remote ischaemic preconditioning (RIPC) is a novel intervention that involves cycles of non-injurious limb ischaemia, achieved via repeated inflation and deflation of a blood pressure cuff, prior to the onset of injurious organ ischaemia. A number of clinical studies have demonstrated that RIPC safely confers a short term protective effect against subsequent injurious IRI at a remote site such as the heart or kidney. The clinical trial ERICCIN, presented within this manuscript, was a multi centre double-blinded randomised controlled study investigating whether RIPC could safely reduce the incidence of CIN in 100 patients with impaired renal function undergoing elective or emergency coronary angiography or PCI at three cardiac centres in south east England in 2015/16. Both study and sham groups received optimal prophylactic measures against CIN. The RIPC/sham procedure was delivered by a novel automated device developed specifically for the study, with RIPC therapy being well tolerated and no complications were reported. The primary outcome measure was reduction in the incidence of CIN at 48 hours, defined as serum creatinine elevation >25% or 0.5g/dl (44µmol/l) above baseline. The secondary outcome measures included changes from baseline in serum serum creatinine/eGFR, urine albumi at 48 hours and at 3 months as well as cardio-renal endpoints. The study was inadvertently underpowered and no difference in primary or secondary outcome measures was demonstrated between RIPC and sham groups, although a trend towards benefit was seen in the RIPC group. Subgroup analysis suggested significant abrogation in acute microalbuminuria in participants with pre-exisiting heart failure receiving RIPC, although the small number of participants meant no conclusions could be drawn this may be hypothesis forming for future studies. The study included a comprehansive audit cycle, local education programme and participant feedback group meetings which are presented withtin the manuscript. The study mandated 100% compliance with optimal prophylactic stategies against CIN resulting in significantly reduced incidence of CIN from 15% to 5%, which was an unexpected but welcome finding which justifies full implementation of current clinical guidance in this field of practice.

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