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Original Investigation
February 5, 2020

Cardiovascular Functional Reserve Before and After Kidney Transplant

Author Affiliations
  • 1Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
  • 2Department of Medicine, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, United Kingdom
  • 3Division of Biomedical Sciences, University of Warwick, Coventry, United Kingdom
  • 4Pragmatic Clinical Trials Unit, Centre for Primary Care and Public Health, Queen Mary, University of London, London, United Kingdom
  • 5Department of Nephrology, University Hospital Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom
  • 6Department of Cardiology, University Hospital Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom
  • 7Research Institutes of Sports and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
  • 8Department of Pathology Service, University Hospital Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom
  • 9Division of Cardiology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
  • 10Centre for Innovative Research Across the Life Course, Coventry University, Coventry, United Kingdom
  • 11Department of Nephrology, North Cumbria University Hospital National Health Service Trust, Carlisle, United Kingdom
  • 12Department of Acute Medicine, North Cumbria University Hospital National Health Service Trust, Carlisle, United Kingdom
  • 13Cambridge Clinical Trials Unit and School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
JAMA Cardiol. Published online February 5, 2020. doi:10.1001/jamacardio.2019.5738
Key Points

Question  How is kidney transplant associated with cardiovascular functional reserve?

Findings  In this cohort study of 166 patients with stage 5 chronic kidney disease and 87 patients with hypertension only to assess change to cardiovascular functional reserve after improving the uremic milieu through a kidney transplant using state-of-the-art cardiopulmonary exercise testing, improved cardiovascular functional reserve was seen 1 year after kidney transplant in the absence of significant alterations in left ventricular morphologic findings.

Meaning  Improved cardiovascular reserve after kidney transplant may be associated with ultrastructural and functional alterations to the cardiovascular system and may not be associated with a change in left ventricular muscle mass.

Abstract

Importance  Restitution of kidney function by transplant confers a survival benefit in patients with end-stage renal disease. Investigations of mechanisms involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac magnetic resonance imaging and have provided conflicting results to date.

Objectives  To evaluate cardiovascular functional reserve in patients with end-stage renal disease before and after kidney transplant and to assess functional and morphologic alterations of structural-functional dynamics in this population.

Design, Setting, and Participants  This prospective, nonrandomized, single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included patients with stage 5 chronic kidney disease (CKD) who underwent kidney transplant (KTR group), patients with stage 5 CKD who were wait-listed and had not undergone transplant (NTWC group), and patients with hypertension only (HTC group) seen at a single center from April 1, 2010, to January 1, 2013. Patients were followed up longitudinally for up to 1 year after kidney transplant. Clinical data collection was completed February 2014. Data analysis was performed from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective data was performed from June 1, 2017, to July 31, 2019.

Main Outcomes and Measures  Cardiovascular functional reserve was objectively quantified using state-of-the-art cardiopulmonary exercise testing in parallel with transthoracic echocardiography.

Results  Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141 [55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC group. At baseline, mean (SD) maximum oxygen consumption (V̇O2max) was significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min−1 · kg−1; NTWC, 18.9 [4.7] mL · min−1 · kg−1) compared with the HTC group (24.9 [7.1] mL · min−1 · kg−1) (P < .001). Mean (SD) cardiac left ventricular mass index was higher in patients with CKD (KTR group, 104.9 [36.1] g/m2; NTWC group, 113.8 [37.7] g/m2) compared with the HTC group (87.8 [16.9] g/m2), (P < .001). Mean (SD) left ventricular ejection fraction was significantly lower in the patients with CKD (KTR group, 60.1% [8.6%]; NTWC group, 61.4% [8.9%]) compared with the HTC group (66.1% [5.9%]) (P < .001). Kidney transplant was associated with a significant improvement in V̇O2max in the KTR group at 12 months (22.5 [6.3] mL · min−1 · kg−1; P < .001), but the value did not reach the V̇O2max in the HTC group (26.0 [7.1] mL · min−1 · kg−1) at 12 months. V̇O2max decreased in the NTWC group at 12 months compared with baseline (17.7 [4.1] mL · min−1 · kg−1, P < .001). Compared with the KTR group (63.2% [6.8%], P = .02) or the NTWC group (59.3% [7.6%], P = .003) at baseline, transplant was significantly associated with improved left ventricular ejection fraction at 12 months but not with left ventricular mass index.

Conclusions and Relevance  The findings suggest that kidney transplant is associated with improved cardiovascular functional reserve after 1 year. In addition, cardiopulmonary exercise testing was sensitive enough to detect a decline in cardiovascular functional reserve in wait-listed patients with CKD. Improved V̇O2max may in part be independent from structural alterations of the heart and depend more on ultrastructural changes after reversal of uremia.

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