Hemodialysis is associated with significant circulatory stress that could produce recurrent and cumulative ischemic insults to multiple organs, such as the brain. We aimed to characterize hemodialysis-induced brain injury by longitudinally studying the effects of hemodialysis on brain white matter microstructure and further examine if the use of cooled dialysate could provide protection against hemodialysis-associated brain injury. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Brain white matter microstructure was studied by diffusion tensor magnetic resonance imaging at baseline and follow-up (38 patients available for paired analysis). Intradialytic hemodynamic stress was quantified using the extrema points analysis model. Patients on hemodialysis exhibited a pattern of ischemic brain injury (increased fractional anisotropy and reduced radial diffusivity). Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability (higher mean arterial pressure extrema points frequencies were associated with higher fractional anisotropy [peak r=0.443, P,0.03] and lower radial diffusivity [peak r=20.439, P,0.02]). Patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year. Our data suggest that hemodialysis results in significant brain injury and that improvement in hemodynamic tolerability achieved by using cooled dialysate is effective at abrogating these effects. This intervention can be delivered without additional cost and is universally applicable.

Background and objectives Cardiovascular disease is the most common cause of death in patients on hemodialysis (HD). HD-associated cardiomyopathy is appreciated to be driven by exposure to recurrent and cumulative ischemic insults resulting from hemodynamic instability of conventionally performed intermittent HD treatment itself. Cooled dialysate reduces HD-induced recurrent ischemic injury, but whether this confers long-term protection of the heart in terms of cardiac structure and function is not known.Design, setting, participants, & measurements Between September 2009 and January 2013, 73 incident HD patients were randomly assigned to a dialysate temperature of 37°C (control) or individualized cooling at 0.5°C below body temperature (intervention) for 12 months. Cardiac structure, function, and aortic distensibility were assessed by cardiac magnetic resonance imaging. Mean between-group difference in delivered dialysate temperature was 1.2°C60.3°C. Treatment effects were determined by the interaction of treatment group with time in linear mixed models.Results There was no between-group difference in the primary outcome of left ventricular ejection fraction (1.5%; 95% confidence interval, -4.3% to 7.3%). However, left ventricular function assessed by peak systolic strain was preserved by the intervention (-3.3%; 95% confidence interval, -6.5% to -0.2%) as was diastolic function (measured as peak diastolic strain rate, 0.18 s 21 ; 95% confidence interval, 0.02 to 0.34 s 21 ). Reduction of left ventricular dilation was demonstrated by significant reduction in left ventricular end-diastolic volume (-23.8 ml; 95% confidence interval, -44.7 to -2.9 ml). The intervention was associated with reduced left ventricular mass (-15.6 g; 95% confidence interval, -29.4 to -1.9 g). Aortic distensibility was preserved in the intervention group (1.8 mmHg 21 310 23 ; 95% confidence interval, 0.1 to 3.6 mmHg 21 310 23 ). There were no intervention-related withdrawals or adverse events.

Summary Background and objectives Circulating troponin T levels are frequently elevated in patients undergoing long-term dialysis. The pathophysiology underlying these elevations is controversial. Design, setting, participants, & measurements In 70 prevalent hemodialysis (HD) patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. Nineteen patients were not available for the follow-up analysis. The extent to which predialysis troponin T was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. Results The median troponin T level in this hemodialysis cohort was 0.06 ng/ml (interquartile range, 0.02–0.10). At baseline, 64% of patients experienced myocardial stunning. These patients showed significantly higher troponin T levels than patients without stunning (0.08 ng/ml [0.05–0.12] versus 0.02 ng/ml [0.01–0.05]). Troponin T levels were significantly correlated to measures of myocardial stunning severity (number of affected segments: r=0.42; change in ejection fraction from beginning of dialysis to end of dialysis: r=−0.45). In receiver-operating characteristic analyses, predialytic troponin T achieved an area under the curve of 0.82 for the detection of myocardial stunning. In multivariable analysis, only ultrafiltration volume (odds ratio, 4.38 for every additional liter) and troponin T (odds ratio, 9.33 for every additional 0.1 ng/ml) were independently associated with myocardial stunning. After 12 months, nine patients had newly developed myocardial stunning and showed a significant increase in troponin T over baseline (0.03 ng/ml at baseline versus 0.05 ng/ml at year 1). Conclusions Troponin T levels in HD patients are associated with the presence and severity of HD-induced myocardial stunning.

Cardiovascular disease is the most common cause of the greatly elevated rates of mortality characteristic of patients undergoing maintenance hemodialysis. This article is an attempt to describe the complex and evolving features of cardiac disease routinely encountered in HD patients. Furthermore, by trying to appreciate the pathophysiological drivers, and the crucial interaction with the HD treatment itself, this article seeks to define cardiac disease in this setting (HD-associated cardiomyopathy) as a unique and complex entity. By understanding the phenotype and basis of HD-associated cardiomyopathy, we can develop an evolved understanding of the dominant processes involved in its development and offer up dialysis-based interventions specifically designed to mitigate the cumulative ischemic insults consequent to conventional HD treatment. This article explores the justification of this approach and recent evidence of its efficacy.

Cardiac dysfunction is a key factor in the high morbidity and mortality rates seen in hemodialysis (HD) patients. Much of the dysfunction is manifest as adverse changes in cardiac and vascular structure prior to commencing dialysis. This adverse vascular remodeling arises as a dysregulation between pro-and anti-proliferative signaling pathways in response to hemodynamic and non-hemodynamic factors. The HD procedure itself further promotes cardiomyopathy by inducing hypotension and episodic regional cardiac ischemia that precedes global dysfunction, fibrosis, worsening symptoms and increased mortality. Drug-based therapies have been largely ineffective in reversing HD-associated cardiomyopathy, in part due to targeting single pathways of low yield. Few studies have sought to establish natural history and there is no framework of priorities for future clinical trials. Targeting intra-dialytic cardiac dysfunction by altering dialysate temperature, composition or ultrafiltration rate might prevent the development of global cardiomyopathy, heart failure and mortality through multiple pathways. Novel imaging techniques show promise in characterizing the physiological response to HD that is a unique model of repetitive ischemia-reperfusion injury. Reducing HD-associated cardiomyopathy may need a paradigm shift from empirical delivery of solute clearance to a personalized therapy balancing solute and fluid removal with microvascular protection. This review describes the evidence for intra-dialytic cardiac dysfunction outlining cardioprotective strategies that extend to multiple organs with potential impacts on exercise tolerance, sleep, cognitive function and quality of life. Intradialytic Cardiac Dysfunction

ObjectivesCardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD.MethodsFifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined.ResultsGlobal systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s-1 versus 1.31 ± 0.38s-1, p = 0.003). LV mass index was increased (63[54,79]g/m2 versus 46[42,53]g/m2, p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity.ConclusionPatients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy.Key Points• First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients.• Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV.• Reductions in strain localised to the septal and anterior wall.• Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms.• Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-015-4096-2) contains supplementary material, which is available to authorized users.

• The pathophysiology underlying chronic cardiorenal syndrome is not completely understood. • Chronic cardiorenal syndrome is independent of cardiac output or renal perfusion. • Renal T 1 relaxation appears to be prolonged in HF with renal impairment. • Renal T 1 relaxation is associated with classic cardiovascular risk factors. • Association of renal T 1 relaxation with parenchymal damage should be validated further.

Patients with chronic kidney disease are well recognized to develop a wide range of cardiac structural and functional abnormalities. These changes may be progressive and relate directly to a grossly aggravated risk of cardiovascular events and reduced survival. Although conventional methods of cardiac assessment have been shown to be useful, they are limited by insufficient sensitivity and specificity, to fully appreciate the overall degree of myocardial distress that is common in these patients. This article aims to review the use of established and emerging cardiac imaging tools and, in particular, their application in patients with chronic kidney disease.