P0917N-ACETYL CYSTEINE FAILS TO IMPACT ON PLASMA ANTIOXIDANT CAPACITY IN BOTH A PLACEBO CONTROLLED CROSSOVER STUDY AND A PARALLEL GROUP TRIAL OF PATIENTS WITH CKD STAGE III: IMPLICATIONS FOR ITS USE AS A PROPHYLACTIC FOR CONTRAST INDUCED NEPHROPATHY

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2020-06, Vol.35 (Supplement_3)
• Main Authors: Raja, Khuram, Hickson, Kirsty, Treweeke, Andrew, Rushworth, Gordon, Morrison, Emma, Sandilands, Euan, Cobley, James, McEneaney, David, Eddleston, Michael, Megson, Ian
• Format: Article
• Language: English
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfaa142.P0917

Abstract This project has been funded by the EU’s INTERREG VA programme, managed by the special EU Programmes Body (SEUPB) Background and Aims N-acetyl-L-cysteine (NAC) has been proposed as a prophylactic for the prevention of contrast induced nephropathy (CIN), a serious, adverse complication following administration of contrast media in patients with diabetes and chronic kidney disease (CKD). However, clinical trial results have failed to demonstrate consistently the beneficial qualities of NAC in this setting. The suggested mechanism by which NAC has been proposed to be effective is via antioxidant activity, but NAC itself appears not to be a powerful antioxidant; intracellular conversion of NAC to glutathione (GSH) is essential for antioxidant effects. We tested the hypothesis that oral or intravenous NAC fails to increase antioxidant activity in the plasma of healthy volunteers or CKD stage III patients undergoing elective coronary angiography. Method 16 healthy volunteers (8 receiving contrast media) and 8 patients with chronic renal failure were recruited to 3 separate groups as a part of a crossover design study. 66 patients with CKD stage III undergoing elective coronary angiography were recruited to a parallel group randomized controlled trial. Each volunteer or patient was randomised to receive NAC (i.v.; 50 mg/kg/hr infusion for 2 h, followed by 20 mg/kg/hr infusion for a further 5 h), or NAC (oral; 1200 mg twice daily, commencing the day before the study visit) or placebo. Participants attended the Clinical Research Facility on three occasions for the crossover groups, but only once in the parallel group trial. Patients were infused with para-aminohippurate (PAH) and inulin to enable measurement of renal function parameters. Plasma and paired buffy coat samples were collected at several time points for 2 hours before contrast infusion and for 6 hours after. Samples were used to measure various clinical parameters, along with intracellular and plasma thiol concentrations and the plasma antioxidant capacity (oxygen radical antioxidant capacity; ORAC). Results Plasma NAC concentrations peaked at 222 µM (healthy volunteers), 354 µM (CKD patients), 271 µM (healthy volunteers receiving contrast) and 348 µM (CKD patients undergoing elective coronary angiography) following infusion of NAC. The corresponding peak concentrations were ∼2 µM following oral NAC across all groups. No comparable increase in the plasma compartment ORAC antioxidant capacity wa