rhErythropoietin-b as a tissue protective agent in kidney transplantation: a pilot randomized controlled trial

Autor: Declan de Freitas, Stephen A Roberts, Paul Brenchley, B. Coupes, Ian Read, M. Picton, Hany Riad
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Graft Rejection
Male
Pathology
genetic structures
Pilot Projects
Kidney
Kidney Function Tests
Ischaemia reperfusion
chemistry.chemical_compound
Medicine
Hepatitis A Virus Cellular Receptor 1
Kidney transplantation
Medicine(all)
Membrane Glycoproteins
Acute kidney injury
Interleukin-18
General Medicine
Middle Aged
Lipocalins
Tissue Donors
medicine.anatomical_structure
Creatinine
Receptors
Virus
Female
medicine.drug
Research Article
medicine.medical_specialty
Urology
Renal function
Delayed Graft Function
Protective Agents
General Biochemistry
Genetics and Molecular Biology
Double-Blind Method
Lipocalin-2
Proto-Oncogene Proteins
Humans
Kidney surgery
Erythropoietin
Aged
Biochemistry
Genetics and Molecular Biology(all)
urogenital system
business.industry
Kidney metabolism
medicine.disease
Kidney Transplantation
chemistry
business
Biomarkers
Acute-Phase Proteins
Zdroj: BMC Research Notes
ISSN: 1756-0500
Popis: Background Extended criteria donor (ECD) and donation after circulatory death (DCD) kidneys are at increased risk of delayed graft function (DGF). Experimental evidence suggests that erythropoietin (EPO) attenuates renal damage in acute kidney injury. This study piloted the administration of high dose recombinant human EPO-beta at implantation of ECD and DCD kidneys, and evaluated biomarkers of kidney injury post-transplant. Methods Forty patients were randomly assigned to receive either rhEPO-b (100,000 iu) (n = 19 in the intervention group, as 1 patient was un-transplantable post randomisation), or placebo (n = 20) in this, double blind, placebo-controlled trial at Manchester Royal Infirmary from August 2007 to June 2009. Participants received either an ECD (n = 17) or DCD (n = 22) kidney. Adverse events, renal function, haematopoietic markers, and rejections were recorded out to 90 days post-transplant. Biomarkers of kidney injury (neutrophil gelatinase-associated lipocalin, Kidney Injury Molecule-1 and IL-18) were measured in blood and urine during the first post-operative week. Results The incidence of DGF (53% vs 55%) (RR = 1.0; CI = 0.5-1.6; p = 0.93) and slow graft function (SGF) (32% vs 25%) (RR = 1.1; CI = 0.5-1.9; p = 0.73) respectively, serum creatinine, eGFR, haemoglobin and haematocrit, blood pressure, and acute rejection were similar in the 2 study arms. High dose rhEPO-b had little effect on the temporal profiles of the biomarkers. Conclusions High dose rhEPO-b appears to be safe and well tolerated in the early post- transplant period in this study, but has little effect on delayed or slow graft function in recipients of kidneys from DCD and ECD donors. Comparing the profiles of biomarkers of kidney injury (NGAL, IL-18 and KIM-1) showed little difference between the rhEPO-b treated and placebo groups. A meta-analysis of five trials yielded an overall estimate of the RR for DGF of 0.89 (CI = 0.73; 1.07), a modest effect favouring EPO but not a significant difference. A definitive trial based on this estimate would require 1000-2500 patients per arm for populations with base DGF rates of 50-30% and 90% power. Such a trial is clearly unfeasible. Trial registration EudraCT Number 2006-005373-22 ISRCTN ISRCTN85447324 registered 19/08/09.
Databáze: OpenAIRE
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