Cardiovascular Functional Reserve Before and After Kidney Transplant.

Lim K, Ting SMS, Hamborg T, McGregor G, Oxborough D, Tomkins C, Xu D, Thadhani R, Lewis G, Bland R, Banerjee P, Fletcher S, Krishnan NS, Higgins R, Zehnder D, Hiemstra TF.

JAMA Cardiol. 2020 Feb 5. doi: 10.1001/jamacardio.2019.5738. [Epub ahead of

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
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
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.