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Am Heart J. 2014 Feb;167(2):141-149.e2. doi: 10.1016/j.ahj.2013.10.024. Epub 2013 Nov 6.

Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: rationale and design of the EARNEST study.

Author information

  • 1Birmingham Cardio-Renal Group, Centre for Clinical Cardiovascular Science, Nuffield House, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
  • 2Cambridge Clinical Trials Unit, Clinical School, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
  • 3BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
  • 4Clinical Science Research Laboratory, University of Warwick, Coventry, United Kingdom.
  • 5Academic Renal Unit, Learning and Research, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom.
  • 6Department of Cardiology, Wales Heart Research Institute, University Hospital, Cardiff, United Kingdom.
  • 7Birmingham Cardio-Renal Group, Centre for Clinical Cardiovascular Science, Nuffield House, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. Electronic address: john.townend@uhb.nhs.uk.

Abstract

BACKGROUND:

There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group.

HYPOTHESES:

The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure.

METHODS:

This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease.

CONCLUSIONS:

These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program (NCT01769924).

PMID:
24439974
PMCID:
PMC3904213
DOI:
10.1016/j.ahj.2013.10.024
[PubMed - indexed for MEDLINE]
Free PMC Article
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