Key Takeaways

  • This prospective, controlled study of 253 patients examined whether kidney transplant is linked to improved cardiovascular reserve
  • The reduction in cardiovascular mortality associated with kidney transplant might be attributable to improved cardiovascular functional reserve rather than structural alterations of the heart
  • The same measures significantly declined in patients with end-stage renal disease who did not undergo transplant
  • Two measures of cardiovascular reserve, maximum oxygen consumption (VO2Max) and oxygen consumption at the point of anaerobic threshold (VO2AT), significantly improved over the 12 months after transplant

Patients with chronic kidney disease (CKD) are at significant risk of premature cardiovascular (CV) death, which is reduced by kidney transplant. Studies investigating the mechanisms of the reduction have had conflicting results, possibly because most have imaged cardiac structure at rest, rather than assess function under stress of exercise.

Kenneth Lim, MD, PhD, physician-scientist in the Division of Nephrology at Massachusetts General Hospital, and Thomas F. Hiemstra, PhD, FRCPE, of the School of Clinical Medicine, University of Cambridge, and colleagues took another approach. They hypothesized that kidney transplant might be linked to improved CV reserve, and they conducted the first prospective, longitudinal cohort study, named the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, to evaluate this question using cardiopulmonary exercise testing (CPET), which measures ventilatory gas exchange during graded exercise.

In JAMA Cardiology, the research team reports that patients with CKD who underwent transplantation showed significant improvement in two objective measures of CV functional reserve without major changes in ventricular structural morphologic features.

Study Methods

The CAPER study evaluated three groups:

  • 81 adults with end-stage renal disease who underwent kidney transplant ("transplant group")
  • 85 wait-listed adults with end-stage renal disease who did not undergo transplant during the study period ("non-transplant group")
  • 87 patients recruited through a primary care database who had hypertension but not CKD, CV disease or diabetes ("hypertension group")

All participants underwent CPET and echocardiography at baseline and after two and 12 months, except that patients in the hypertension group were excluded from the two-month assessment. Patients were followed for up to one year after kidney transplant.

The primary outcomes in this study were change in maximum oxygen consumption (VO2Max) and oxygen consumption at the point of anaerobic threshold (VO2AT), which reflect cardiac pumping capacity, oxygen delivery and oxygen use.

CV Reserve

When adjusted for other risk factors, both measures of CV functional reserve showed significant improvement between baseline and 12 months in the transplant group and significant declines in the non-transplant group.

However, cardiovascular functional reserve in patients in the transplant group did not return to levels observed in the hypertension group. That finding was consistent with incomplete normalization of kidney function after transplant—the average eGFR at 12 months was 59.1 mL/min/1.73 m3, representing CKD stage 3.

Echocardiographic Measures

In the transplant group, there was a subtle improvement in average left ventricular ejection fraction from baseline to 12 months (60.0% to 63.2%; P = .02) as well as compared with the 12-month value in the non-transplant group, which was 59.3% (P = .003).

In the adjusted model, a transplant was not associated with a change in left ventricular muscle mass at any time.

Clinical Relevance of the Findings

The reduction in cardiovascular mortality associated with kidney transplant might be attributable to improved cardiovascular functional reserve rather than structural alterations of the heart. This suggests it may be possible to pinpoint new therapeutic targets for improving cardiovascular outcomes in patients with CKD.

In the shorter term, CPET seems to be a sensitive way to assess CV function in patients with CKD, such as for risk stratification in clinical trials.