Cardiovascular Functional Reserve Improves After Kidney Transplant

Megan Brooks

February 11, 2020

Cardiovascular functional reserve improves after kidney transplantation in patients with end-stage renal disease (ESRD), even in the absence of significant alterations in left ventricular morphology, according to results of the CAPER study.

Maximum oxygen consumption, measured using state-of-the cardiopulmonary exercise testing (CPET) indices, was significantly better at 1 year in patients underwent kidney transplantation than in those who did not.

Left ventricular function also improved with transplantation, but without changes in left ventricular mass.

"CPET indices, particularly VO2 max [maximum oxygen consumption], appear to capture ultrastructural changes resulting from the reversal of the uremic milieu by transplantation," Thomas F. Hiemstra, PhD, Cambridge Clinical Trials Unit, Addenbrooke's Hospital, United Kingdom, told | Medscape Cardiology.

"CPET may be a sensitive tool to evaluate cardiovascular functional capacity in patients with chronic kidney disease [CKD], or indeed may be a sensitive surrogate end point for cardiovascular outcomes in clinical trials in patients with CKD," Hiemstra said.

The CAPER study results were published online February 5 in JAMA Cardiology.

Conflicting Data

Cardiovascular disease is the leading cause of death among patients with CKD. A new, well-functioning kidney mitigates the cardiovascular risk associated with advanced CKD, but why and how remain an open question.

Studies that have tried to get at the mechanism(s) involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac MRI and have provided conflicting results to date, the investigators note. In the CAPER study, cardiovascular functional reserve was objectively quantified using state-of-the-art CPET in parallel with transthoracic echocardiography.

The study team characterized changes in cardiovascular reserve before and after kidney transplantation in 81 patients with ESRD who underwent kidney transplant, and compared them with 85 wait-listed control patients with ESRD who did not undergo transplantion (NTWC group) and 87 control subjects with hypertension and preserved kidney function (HTC group).

Transplantation was also associated with a restoration of estimated glomerular filtration rate (eGFR) at 2 months (55.3 mL/min per 1.73 m2) and 12 months (59.1 mL/min per 1.73 m2).

At baseline, average VO2 max was significantly lower (P < .001) and average cardiac left ventricular mass index was significantly higher (P < .001) in the ESRD groups than in the HTC control group. Average left ventricular ejection fraction was also significantly lower in the ESRD groups than in the HTC group (P < .001).

At 1 year, kidney transplantation was associated with a significant improvement in VO2 max (from 20.7 to 22.5 mL·min−1·kg−1; < .001), but the value did not reach the VO2 max in the HTC group (24.9 at baseline and 26.0 mL·min−1·kg−1 at 1 year). In the NTWC group, VO2 max decreased at 1 year, compared with baseline (from 18.9 to 17.7 mL·min−1·kg−1; < .001).

Transplant-associated improvements over time in the cardiovascular reserve indexes of VO2 max and oxygen consumption at the point of anaerobic threshold (VO2 AT), as well as oxygen pulse (a measure of oxygen consumption per heart beat) at maximal exercise, tolerated workload, and endurance time were significant even after adjustment for age, body mass index, sex, smoking, diabetes, CVD, duration of antihypertensive therapy, beta-blocker use, hemoglobin level, and length of time patients are receiving dialysis, the investigators report.

With kidney transplantation, left ventricular ejection fraction was also significantly improved at 1 year (from 60.0% to 63.2%; P = .02), but with no significant change in left ventricular mass index.

"Taken together, the marked changes in measures of functional cardiovascular reserve and the subtle difference in LVEF in the absence of other significant structural echocardiographic changes reported here suggest that the reduction in cardiovascular mortality associated with kidney transplant may be explained by improved cardiovascular functional reserve," Hiemstra and colleagues write.

"Exciting" Findings

These results are "exciting" as they demonstrate improved cardiovascular functional reserve after transplant despite the absence of left ventricular mass reduction, George L. Bakris, MD, and Michelle A. Josephson, MD, University of Chicago Medicine, write in an invited commentary in JAMA Cardiology.

Although several factors likely contribute to this benefit, reduced inflammation and anemia burden are likely "pivotal elements associated with this benefit. Whatever the cause, improved kidney function after kidney transplantation may be associated with improved cardiovascular functional reserve, even if the left ventricular mass does not change," Bakris and Josephson say.

However, they urge caution in interpreting the results for three reasons.

"First, these individuals overwhelmingly received living donor kidneys; thus, it is unclear whether these outcomes would be similar if deceased donor kidneys were implanted," they point out.

"Second, approximately one-third preemptively underwent transplant, and the remainder had relatively short dialysis duration (ie, mean of <3 years). This scenario is not typical for transplant in the United States," they note.

"Third, the transplant group studied was 81.5% white. Consequently, it is unclear whether these findings would be translatable to a more typical transplant cohort," they add.

The CAPER study was funded by a grant from the British Heart Foundation. The Reading family and University Hospital Coventry and Warwickshire National Health Service Trust Charity funded the CPET machine used in this study. Hiemstra has receiv ed grants from the National Institute of Health Research, Kidney Research UK, AstraZeneca, and Vifor Pharma. Bakris has received personal fees from Merck and Relypsa. Josephson has no disclosures.

JAMA Cardiol. Published online February 5, 2020. Abstract, Commentary


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: