This study demonstrates that impaired GLS occurs in nearly 40% of KTx patients with preserved LVEF. The GLS impairment is related to the presence and duration of HD before KTx and kidney allograft function assessed by eGFR.
In our study, the majority of KTx patients had severe LVH. The severity of LVH did not correlate with the impaired GLS. LVMI was comparable in patients with or without impaired GLS.
Impaired GLS in CKD patients is an indicator of decreased LV contractility probably due to LV remodelling with increased accumulation of extracellular matrix and myocardial fibrosis. Recently, Sandal et al. found that congestive heart failure, but not the coronary artery disease, is the most common cause of cardiovascular events following KTx [9]. That finding confirms earlier outcomes of studies based on the United States Renal Data System conducted on thousands of patient [10]. The consensus was that the KTx is a state of “accelerated heart failure” rather than “accelerated atherosclerosis”.
The advantages of LV GLS over LVEF in the assessment of LV systolic function have been demonstrated in several studies in general population as well as cardiac disease and in CKD patients. Previously reported prevalence of impairment of LV GLS in CKD patients with preserved LVEF was between 17 and 60%. The differences could be attributed to the selection of CKD patients for the studies (with various stages of CKD from 1 to 5, involving patients with cardiac morbidity e.g. history of myocardial infarction, CABG, atrial fibrillation, heart failure), and various cut-off values of GLS (-18 to -15%).Panoulas et al. in their study carried out on 106 CKD patients with LVEF≥55% and no history of cardiovascular disease or its symptoms, defined the GLS impairment as values greater than -16% [11]. The incidence of impaired GLS was dependent on the CKD stage and was only 3.4% in stage 1 or 2, 39.5% in stage 3, and 25.6% in stage 4 and 5. While the greatest LVMI was observed in patient 4-5stage. In patients with impaired GLS, the authors observed an increased rate of adverse cardiovascular events (including general mortality, coronary artery disease, and length of hospitalization for heart failure) during follow-up of 30.7±11.7 months. They also suggested that impaired GLS may be a result of microvascular ischemia and myocardial fibrosis as the studied group did not have an evident disease in epicardial arteries, which had been confirmed by elective angiography.,Hensen et al. showed LV systolic dysfunction defined by LV GLS ≤15.2%. in 32% of predialysis and dialysis patients with LV ejection fraction ≥50% [12]. Ravera et al. observed GLS impairment (defining the cut-off of GLS impairment value on less than -18%) in 55% of CKD patients in stage 2-4 and in 60% of dialysed patients [13].In kidney transplant patients, according to various studies the value of GLS was -17 to -19%, because CKD patients with lower GLS were less frequently transplanted. In Hensen study, only 8% patients with GLS < 10.6% were transplanted, while 32% with GLS 10.7-15.1%; 49% with GLS 15.2-17.8%, and 47% with GLS > 17.9% [14].
Many previous studies have shown that KTx has a beneficial effect on LV structure and function compared to dialysis. The studies based on a series of conventional echocardiograms showed an improvement in LVEF after KTx. Ravinder et al. showed improvement not only in LVEF but also in functional status of heart failure and increased survival rate after KTx [15]. Paoletti et al. in their study also proved that the LVH regression following KTx was a predictor of a better long-term clinical outcome [16]. However, the LVM regression has not been confirmed by CMR what may raise doubts about the reversibility of LVH in transplant patients [17].
It has not been established whether GLS ameliorates following KTx. There are only few studies presenting GLS in small groups of patients before and after KTx. A retrospective study of Hewing et al. showed improvement of LV global longitudinal peak systolic strain (GLPS) after KTx [18]. They evaluated a group of 31 CKD patients at mean age 44 years before and 13-32 (mean 19) months after successful KTx and found significant improvement in LV systolic function assessed by GLS (-18.4%±2.8% vs -19.4%±2.3%). Concomitantly, reduction of LV end-diastolic septal and posterior wall thickness and LVMI were observed. In that study 8 patients (25%) had preemptive KTx.
The analysis of LV systolic function assessed by speckle-tracking echocardiography was reported in pediatric patients with stage 3-5 CKD, during dialysis treatment, and after KTx. The study revealed higher impairment of GLS in patients on dialysis than in stage 3-5 CKD and in patients after KTx. One year after KTx, children presented impairment of GLS similar to stage 3-5 CKD, suggesting improvement of LV function. However, it cannot be determined whether impaired systolic contractility assessed by GLS did improve after KTx (in comparison to dialysis children) because 42% of patients (18 out of 42) had preemptive KTx [19].
Contrary to these studies, Gong et al. presented greater impairment of GLS in kidney transplant patients. They conducted a prospective study in 39 patients (mean age 47 years) who underwent KTx. LV GLS was assessed by cardiovascular magnetic resonance imaging (CMRI) at baseline and at 12 months after KTx. Kidney transplant patients had decline in GLS over 12 months (-15.9%±3% vs -14.9%±3%) post transplantation, although LVEF and LV volumes improved, pointing to a reduction of LVH [20].
We found a significant correlation between the impairment of GLS and duration of HD before KTx. Long HD time (> 27,5 months) increased the incidence of impaired GLS suggesting that the structural abnormalities of myocardium progress on HD and fail to subside after KTx. In contrast, ten patients with preemptive KTx had normal GLS value, although they were mean 95 months after transplantation and had lower eGFR (41.3 mL/min/1,73m2). Our study for the first time showed the relation of subclinical LV systolic dysfunction with a duration of HD before KTx. Relationship between LVH and duration of HD was reported. Foley et al. showed that after 18 months of dialysis 62% of the patients had increased LV mass volume index and 49% of them developed overt LV failure [21].
Many studies showed, that long time on HD before transplantation is associated with decreased patient and kidney allograft survival. Meier-Krieshe study, including 73,103 patients with the United States Renal Transplant Scientific Registry, evidenced that longer time on HD prior to KTx compared to preemptive KTx was a significant risk factor for the death of patient with a functioning graft (p<0.001). Increase in mortality risk after KTx was 41% for patients on HD for 24-36 months and 72% for patients dialyzed over 48 months relative to preemptive transplantation [22].
Recently, Jay et al. reassessed preemptive KTx using data of 141,254 transplant recipients from United Network of Organ Sharing, who were transplanted between 2003 and 2012. Their retrospective study confirmed that preemptive KTx as well as short time of dialysis < 1 year prior to transplantation in recipients of living kidney donor were associated with higher 5-year patient survival. During the last 2 decades the percentage of patients with preemptive KTx raised from 10.9% to 17% [23].
During HD the patients are exposed to multiple factors such pressure and volume overload, activation of renin-angiotensin system chronic inflammation, hiperhomocysteinemia, advanced glycosylation end products, anemia, endothelial dysfunction, oxidative stress, arteriovenous access. The cumulative effect of these factors leads to cardiac and vascular damage. Dialysis treatment compared to preemptive KTx was associated with increased stiffness and reduced vascular compliance. Yet, the important role of FGF23 should emphasized, which serum level increase over 400 times in hemodialysed patients. FGF23 levels are associated with LVH, and myocardial fibrosis, and increased cardiovascular mortality [24].
In our study value of eGFR > 60mL/min/1.73m2 was a protective factor for the development of subclinical LV systolic dysfunction. The GLS relationship to eGFR in kidney transplant recipients has not been studied so far. However, in CKD patients before transplantation LV systolic function progressed with falling eGFR and was the worst during dialysis. The study of Park et al. proved that the decrease of eGFR >60 mL/ min/1.73 m2 correlate with impaired LV function on follow-up echocardiography [25]. Normal renal function after transplantation reduces the risk of cardiovascular mortality in kidney transplant recipients but injured renal function is a strong risk factor for cardiovascular events and mortality. KTx restores normal renal function (eGFR >90 mL/min/1.73 m2) only in 5% of recipients. The remaining recipients present stage 3A (30%), 3B (18%) and stage 4 (5%) of CKD [26]. Weiner et al. in FAVORIT study showed that decrease of eGFR below 45 mL/min/1.73 m2 is associated with cardiovascular disease and mortality, while increase of eGFR by each 5 mL/min/1.73 m2 above 45mL/ min/1.73 m2, is associated with 15% reduction in CVD and mortality [27].
We also observed that impaired GLS bordeline depend on the time elapsed after KTx. Patients who were transplanted more than 152,5 months had higher occurrence of impaired GLS however in stepwise logistic regression analysis it was not statistically significant.
Ten patients in our study with preemptive KTx had normal GLS, although they were mean 95 months after transplantation and had lower eGFR (41.3 mL/ min/1.73 m2) This outcome emphasises the most harmful role of HD on systolic function on LV