Kristin V Veighey1, Jennifer M Nicholas2, Tim Clayton2, Rosemary Knight2, Steven Robertson2, Neil Dalton3, Mark Harber4, Christopher J E Watson5, Johan W De Fijter6, Stavros Loukogeorgakis7, Raymond MacAllister8. 1. Wessex Kidney Centre, Portsmouth Hospitals NHS Trust, Portsmouth, Hampshire, UK; Research and Development, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK. Electronic address: kristin.veighey@uhs.nhs.uk. 2. Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London, UK. 3. Evelina London Children's Hospital, London, UK. 4. Kidney Unit, Royal Free London NHS Foundation Trust, London, UK. 5. Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 6. Department of Medicine, Division of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands. 7. Institute of Child Health, University College London, London, UK. 8. Dorset County Hospital NHS Foundation Trust, Dorset, UK.
Abstract
BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal functionafter living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS:RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.
RCT Entities:
BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS:RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.
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