Cardiovascular Functional Reserve Before and After Kidney Transplant

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bland reported receiving grants from Abbott Laboratories and Amgen during the conduct of the study. Dr Higgins reported receiving grants from the Reading family during the conduct of the study. Dr Hiemstra reported receiving grants from the National Institute of Health Research, Kidney Research UK, AstraZeneca, and Vifor Pharma outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Changes in Functional Cardiovascular Measures Before and After Kidney Transplant (Adjusted)

Changes in maximum oxygen consumption (V̇O2max) and oxygen consumption at the point of anaerobic threshold (V̇O2AT) over time at baseline (before transplant), 2-month follow-up, and 12-month follow-up. Comparisons were adjusted for age, body mass index, sex, smoking, diabetes, cardiovascular disease, duration of antihypertensive therapy, β-blocker use, hemoglobin level, and dialysis duration. aP value for comparison between 2 groups for changes over time. bP value for comparison between 2 groups at each respective time point.

Figure 2.. Changes in Functional and Structural Cardiovascular Measures Before and After Kidney Transplant

Data are presented as means with 95% CIs (error bars) by group. Changes in maximum oxygen consumption (V̇O2max) and oxygen consumption at the point of anaerobic threshold (V̇O2AT), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF) from baseline (before transplant) to 12-month follow-up, adjusted for age, body mass index, sex, smoking, diabetes, cardiovascular disease, duration of antihypertensive therapy, β-blocker use, hemoglobin level, and dialysis duration. P value for comparison among the 3 groups at 1-year follow-up with time × group interaction using analysis of variance.