Functional Cardiovascular Reserve Predicts Survival Pre-Kidney and Post-Kidney Transplantation

Abstract

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for #5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT ,40% of predicted peak VO 2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT $40% (P,0.001). Regarding the cohort with AT ,40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT $40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

Pre-operative Functional Cardiovascular Reserve Is Associated with Acute Kidney Injury after Intervention

“…A study involving 10,518 patients undergoing surgery suggested that long-term survival was worse those with AKI, even after complete eGFR recovery (43). We have previously shown a strong association between AKI after endovascular intervention, vascular surgery, renal transplantation or coronary angiography and subsequent short and longterm cardiovascular events and all-cause morbidity, in multiple cohort studies as well as a metaanalysis (4,26,28,29). A recent review from NICE suggests that AKI has a major impact on safety and healthcare-cost (44); a patient with AKI after intervention spends an average of 4.7 extra nights hospitalised with an additional £3,691 for medical-treatment (5,44).…”

“…During CPET, exercise sustainability through the aerobic regeneration of ATP is supplemented by anaerobic glycolysis, resulting lactic-acid production. AT represents the upper limit of workload beyond which prolonged exercise is impossible (28). It has been shown to be an objective marker of CVR (19)(20)(21)(22)28).…”

“…AT represents the upper limit of workload beyond which prolonged exercise is impossible (28). It has been shown to be an objective marker of CVR (19)(20)(21)(22)28). Patients undergoing EVAR have a high-prevalence of AKI risk-factors and are at significant risk of AKI (1,14).…”

“…The latter (CPET) is now being used frequently prior to major surgery (20)(21)(22)(23)(24). It provides an accurate estimate of CVR by measuring AT, a validated objective and reproducible marker of CVR, independent patient effort (25)(26)(27)(28)(29).…”

Screening for cardiovascular disease before kidney transplantation

“…Failure to achieve the target heart rate impairs the capture of sufficient diagnostic information [29] , and ambiguity in correlating ECG findings to territorial ischemia will lead to a decision to pursue additional forms of stress testing in most cases. Testing for functional cardiovascular reserve [30,31] instead may be superior for prognostication although these tests have not been widely adapted. Nonetheless, exercise stress testing is reasonable to pursue in young, otherwise apparently healthy transplant candidates by serving as a positive reinforcement to them.…”