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BACKGROUND: Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes. METHODS: One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared. RESULTS: A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m2 post-KT vs. 30.9 mL/m2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT. DISCUSSION/CONCLUSION: Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling.

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The first successful live donor kidney transplant was performed in 1954. Receiving a kidney transplant from a live kidney donor remains the best option for increasing both life expectancy and quality of life in patients with end-stage kidney disease. However, ever since 1954, there have been multiple questions raised on the ethics of live kidney donation in terms of negative impacts on donor life expectancy. Given the close relationship between reduced kidney function in patients with chronic kidney disease (CKD) and hypertension, cardiovascular disease and cardiovascular mortality, information on the impact of kidney donation on these is particularly relevant. In this article, we review the existing evidence, focusing on the more recent studies on the impact of kidney donation on all-cause mortality, cardiovascular mortality, cardiovascular disease and hypertension, as well as markers of cardiovascular damage including arterial stiffness and uraemic cardiomyopathy. We also discuss the similarities and differences between the pathological reduction in renal function that occurs in CKD, and the reduction in renal function that occurs because of a donor nephrectomy. Kidney donors perform an altruistic act that benefits individual patients as well as the wider society. They deserve to have high-quality evidence on which to make informed decisions.

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Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5/6 nephrectomy group (5/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.

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AIMS: Patients undergoing dialysis, even those without coronary artery disease or valvular abnormalities, sometimes present with reduced heart function, which resembles dilated cardiomyopathy (DCM). This condition is known as uraemic cardiomyopathy (UCM). The mechanisms of UCM development are not fully understood. Previous studies demonstrated that the balance between placental growth factor (PlGF) and fms-like tyrosine kinase-1 (Flt-1) is correlated with renal function, and PlGF/Flt-1 signalling is involved in the development of cardiovascular diseases in patients with chronic kidney disease. This study was conducted to evaluate the pathogenesis of UCM and clarify the differences in the mechanisms of UCM and DCM by using human endomyocardial biopsy and blood samples. METHODS AND RESULTS: The clinical and pathological features of 30 patients on dialysis with reduced cardiac function [left ventricular ejection fraction (LVEF) ≤50%] (UCM group; mean age: 58.5 ± 9.4 years and LVEF: 39.1 ± 7.2%), 196 DCM patients (DCM group; mean age: 62.7 ± 14.0 years and LVEF: 33.5 ± 8.8%) as controls with reduced cardiac function (LVEF ≤ 45%), and 21 patients as controls with normal cardiac function (control group; mean age: 56.2 ± 19.3 years and LVEF: 67.5 ± 6.7%) were analysed. The percentage of the interstitial fibrosis area in the UCM group was greater than that in the DCM group (P = 0.045). In UCM patients, the percentage of the interstitial fibrosis area was positively correlated with the duration of renal replacement therapy (P < 0.001). The number of infiltrated CD68-positive macrophages in the myocardium and expression of monocyte chemoattractant protein-1 (MCP-1) in cardiomyocytes were significantly greater in the UCM group than in the other groups (P < 0.001, respectively). Furthermore, while the serum level of soluble form of Flt-1, an endogenous inhibitor of PlGF, in the UCM group was lower compared with that in the DCM group (P < 0.001), the serum levels of PlGF and PlGF/soluble form of Flt-1 ratio and plasma level of MCP-1 in the UCM group were higher than those in the DCM group (P < 0.001, respectively). CONCLUSIONS: These results suggest that activated PlGF/Flt-1 signalling and subsequent macrophage-mediated chronic non-infectious inflammation via MCP-1 in the myocardium are involved in the pathogenesis of UCM.

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Uraemic Cardiomyopathy (UC) is recognised as an intricate and multifactorial disease which portends a significant burden in patients with End-Stage Renal Disease (ESRD). The cardiovascular morbidity and mortality associated with UC is significant and can be associated with the development of arrythmias, cardiac failure and sudden cardiac death (SCD). The pathophysiology of UC involves a complex interplay of traditional implicative factors such as haemodynamic overload and circulating uraemic toxins as well as our evolving understanding of the Chronic Kidney Disease-Mineral Bone Disease pathway. There is an instrumental role for multi-modality imaging in the diagnostic process; including transthoracic echocardiography and cardiac magnetic resonance imaging in identifying the hallmarks of left ventricular hypertrophy and myocardial fibrosis that characterise UC. The appropriate utilisation of the aforementioned diagnostics in the ESRD population may help guide therapeutic approaches, such as pharmacotherapy including beta-blockers and aldosterone-antagonists as well as haemodialysis and renal transplantation. Despite this, there remains limitations in effective therapeutic interventions for UC and ongoing research on a cellular level is vital in establishing further therapies.

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BACKGROUND AND PURPOSE: Klotho is a membrane-bound or soluble protein, originally identified as an age-suppressing factor and regulator of mineral metabolism. Klotho deficiency is associated with the development of renal disease, but its role in cardiac function in the context of uraemic cardiomyopathy is unknown. EXPERIMENTAL APPROACH: We explored the effects of Klotho on cardiac Ca2+ cycling. We analysed Ca2+ handling in adult cardiomyocytes from Klotho-deficient (kl/kl) mice and from a murine model of 5/6 nephrectomy (Nfx). We also studied the effect of exogenous Klotho supplementation, by chronic recombinant Klotho treatment, or endogenous Klotho overexpression, using transgenic mice overexpressing Klotho (Tg-Kl), on uraemic cardiomyopathy. Hearts from Nfx mice were used to study Ca2+ sensitivity of ryanodine receptors and their phosphorylation state. KEY RESULTS: Cardiomyocytes from kl/kl mice showed decreased amplitude of intracellular Ca2+ transients and cellular shortening together with an increase in pro-arrhythmic Ca2+ events compared with cells from wild-type mice. Cardiomyocytes from Nfx mice exhibited the same impairment in Ca2+ cycling as kl/kl mice. Changes in Nfx cardiomyocytes were explained by higher sensitivity of ryanodine receptors to Ca2+ and their increased phosphorylation at the calmodulin kinase type II and protein kinase A sites. Ca2+ mishandling in Nfx-treated mice was fully prevented by chronic recombinant Klotho administration or transgenic Klotho overexpression. CONCLUSIONS AND IMPLICATIONS: Klotho emerges as an attractive therapeutic tool to improve cardiac Ca2+ mishandling observed in uraemic cardiomyopathy. Strategies that improve Klotho availability are good candidates to protect the heart from functional cardiac alterations in renal disease.

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BACKGROUND: In patients with end stage renal disease (ESRD), left ventricular (LV) hypertrophy with impaired LV function, which is called uremic cardiomyopathy (UC) is often observed. The UC historically has been considered a contraindication for kidney transplantation (KTx). Currently, moderate LV dysfunction does not exclude the possibility of KTx. The amelioration of uremia after KTx improved cardiac function in patients with LV dysfunction. There is a little information on the function of the left atrium (LA) after the KTx procedure. There are no studies evaluating (LA) changes in patients with UC after KTx and determining the possibility of inhibiting the occurrence of LA unfavourable changes (remodelling) and even a possible LA recovery process (reverse remodelling) as a result of a successful KTx. The aim of the study was to assess the LA reverse remodelling in patients with ESRD undergoing KTx. METHODS: The study group consisted of 42 patients, aged 43.3 ± 12.6 followed for 36 months after a deceased donor KTx. The patients were studied at five time points: 1, 3, 6, 12 and 36 months after KTx. In all patients transthoracic echocardiography was performed in order to assess the following LA planimetric parameters: LAmax, LAmin, LAwaveP. LAshortmax, LAshortmin, LAshortwaveP, LAlongmax, LAlongmin, LAlongwaveP, LAcircmax and LAareamax, volumentric parameters: LA volume (LAV), LA volume index (LAVI), and hemodynamic indices: LA ejection fraction (LAEF), LA active emptying fraction (LAAE), LA passive emptying fraction (LAPE), LA index of expansion (LAIE) and LA fractional shortening (LAFS). RESULTS: The LAVI values were 34.63 ± 10.34 ml/m2, 32.24 ± 9.59 ml/m2 (p < 0,001), 31.36 ± 9.20 ml/m2 (p < 0,001), 28.29 ± 8.32 ml/m2 (p < 0,001) and 27.57 ± 8.40 ml/m2 (p < 0,001), after: 1, 3, 6, 12 and 36 months after KTx, respectively. The reduction of the LA size was accompanied by gradual LA contractility improvement, which was manifested as an increase of the LA hemodynamic indices such as LAEF, LAAE, LAIE, LAFS and a decrease of LAPE. CONCLUSIONS: LA remodelling secondary to atrial uraemic cardiomyopathy is an example of complex cardiomyopathy with elements characteristic of both congestive and infiltrative cardiomyopathy. Early LAVI reduction post KTx mostly depends on changed haemodynamic conditions, whereas the main reason for further decrease of LAVI values is related to resolution of uraemic toxaemia.

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