Feedback control in hemodialysis.

A number of systems of feedback control during dialysis have been developed, which have the shared characteristic of prospectively measuring physiological parameters and then automatically altering dialysis parameters in real time according to a pre-specified dialysis prescription. These include feedback systems aimed at reducing intradialytic hypotension based on relative blood volume monitoring linked to adjustments in ultrafiltration and dialysate conductivity, and blood temperature monitoring linked to alterations in dialysate temperature. Feedback systems also exist that manipulate sodium balance during dialysis by assessing and adjusting dialysate conductivity. In this review article, we discuss the rationale for automated feedback systems during dialysis, describe how the different feedback systems work, and provide a review of the current evidence on their clinical effectiveness.

Frailty, multimorbidity and sarcopaenia in haemodialysis patients.

PURPOSE OF REVIEW: It is well recognised that haemodialysis patients have higher levels of multimorbidity, frailty and sarcopaenia. This review examines the current understanding of the three concepts in relation to the general population and haemodialysis patients, and the methods used to quantify them. It also looks at the interaction between multimorbidity, frailty and sarcopaenia in this patient group and proposes a new model that utilises muscle mass index and fat mass index as a surrogate representation of the three concepts. RECENT FINDINGS: Multimorbidity in on the rise in the general population and this is one of the contributing factors to higher rates of chronic kidney disease, progression to end-stage renal disease and multimorbidity in haemodialysis patients. Malnutrition and haemodialysis induced end organ damage further contributes to muscle loss and frailty in this patient group. There is a significant overlap and interaction between multimorbidity, frailty and sarcopaenia in haemodialysis and their presence carries a significant impact on quality of life and survival. There are multiple scores for measuring multimorbidity, frailty and sarcopenia and there is no consensus on their utilisation in haemodialysis patients. We propose the use of fat mass index and muscle mass index model as a surrogate method for clinically quantifying multimorbidity, frailty and sarcopaenia. SUMMARY: Effective public health policies are likely to have an impact on reducing the prevalence of multimorbidity and the development of end stage renal disease. Future research is required to develop interventions that are targeted at maintaining muscle mass and function in haemodialysis patients.

Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

OBJECTIVES: Cardiomyopathy 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. METHODS: Fifty-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. RESULTS: Global 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/m(2) versus 46[42,53]g/m(2), 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. CONCLUSION: Patients 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.

The pathophysiology of the chronic cardiorenal syndrome: a magnetic resonance imaging study.

OBJECTIVE: To study the association of renal function with renal perfusion and renal parenchymal structure (T1 relaxation) in patients with chronic heart failure (HF). METHODS: After IRB approval, 40 participants were enrolled according to HF and renal function status [10 healthy volunteers < 40 years; 10 healthy age-matched volunteers; 10 HF patients eGFR > 60 ml/min/1.73 m(2); 10 HF patients eGFR < 60 ml/min/1.73 m(2)] and assessed by MRI. To be eligible for enrolment all HF patients with renal dysfunction (RD) needed to be diagnosed as having chronic cardiorenal syndrome based on current guidelines. Patients with primary kidney disease were excluded. RESULTS: Renal cortical perfusion correlated with eGFR values (r = 0.52;p < 0.01) and was similar between HF patients with and without RD (p = 0.27). T1 relaxation correlated negatively with eGFR values (r = -0.41;p > 0.01) and was higher in HF patients compared to volunteers (1121 ± 102 ms vs. 1054 ± 65 ms;p = 0.03). T1 relaxation was selectively prolonged in HF patients with RD (1169 ms ± 100 vs. HF without RD 1067 ms ± 79;p = 0.047). In linear regression analyses coronary artery disease (p = 0.01), hypertension (p = 0.04), and diabetes mellitus (p < 0.01) were associated with T1 relaxation. CONCLUSION: RD in HF is not primarily mediated by decreased renal perfusion. Instead, chronic reno-parenchymal damage, as indicated by prolonged T1 relaxation, appears to underly chronic cardiorenal syndrome. KEY POINTS: • 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.

Characterising haemodynamic stress during haemodialysis using the extrema points analysis model.

BACKGROUND AND AIMS: It is becoming recognised that the process of haemodialysis (HD) itself induces circulatory stress that could be implicated in the observed higher rate of end-organ damage. We aimed to study the haemodynamic performance during HD using the extrema points (EP) analysis model, and to examine the determinants of the model and its relation to circulatory stress. METHODS: 63 incident HD patients were studied. Mean arterial blood pressure (MAP) EP frequencies and baroreflex sensitivity during HD were computed for continuous non-invasive haemodynamic monitoring. Pulse-wave velocity as a measure of arterial stiffness was performed. High-sensitivity troponin-T was also measured. RESULTS: The time of each dialysis session was divided into four quarters. Repeated measures ANOVA of the MAP EP frequencies for all subjects during HD demonstrated a gradual significant increase reaching peak levels at the third quarter of dialysis time and remaining at that peak during the fourth quarter (F(3,171228) = 392.06, p < 0.001). In multivariate regression, lower baroreflex sensitivity was the only independent predictor of higher MAP EP frequencies (ß = -0.642, p = 0.001, adjusted R(2) for the whole model = 0.385). In linear regression analysis, higher MAP EP frequencies were associated with higher troponin-T levels (ß = 0.442, p = 0.002, R(2) = 0.19, B = 103.29, 95% CI 38.88-167.70). CONCLUSION: The EP analysis model using MAP is a novel functional haemodynamic measure that can represent and quantify circulatory stress during HD. This measure seems to be determined by the integrity of the autonomic function in HD and could represent the link between circulatory stress and end-organ damage in HD patients.

Exploring haemodynamics of haemodialysis using extrema points analysis model.

BACKGROUND: Haemodialysis is a form of renal replacement therapy used to treat patients with end stage renal failure. It is becoming more appreciated that haemodialysis patients exhibit higher rates of multiple end organ damage compared to the general population. There is also a strong emerging evidence that haemodialysis itself causes circulatory stress. We aimed at examining haemodynamic patterns during haemodialysis using a new model and test that model against a normal control. METHODS: We hypothesised that blood pressures generated by each heart beat constantly vary between local peaks and troughs (local extrema), the frequency and amplitude of which is regulated to maintain optimal organ perfusion. We also hypothesised that such model could reveal multiple haemodynamic aberrations during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we compared various haemodynamic parameters using the above model between a haemodialysis patient during a dialysis session and an exercised normal control after comparison at rest. RESULTS: Measurements yielded 29,751 data points for each haemodynamic parameter. Extrema points frequency of mean arterial blood pressure was higher in the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood pressure was significantly higher in haemodialysis compared to normal. In contrary, the frequency of extrema points for TPR was higher in the normal control compared to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly higher amplitudes. CONCLUSION: Haemodialysis patients potentially exhibit an aberrant haemodynamic behaviour characterised by higher extrema frequencies of mean arterial blood pressure and lower extrema frequencies of total peripheral resistance. This, in theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds.

N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis-induced myocardial stunning.

BACKGROUND: Haemodialysis (HD) is able to induce recurrent myocardial ischemia and segmental left-ventricular dysfunction (myocardial stunning). The association of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced myocardial stunning is unclear. METHODS: In 70 prevalent HD patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. The extent to which pre-dialysis NTpro-BNP was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. RESULTS: The median Ntpro-BNP concentration in this cohort was 2,154 pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583-3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not differ between patients showing HD-induced stunning at baseline and those developing stunning during the observational period (p = 0.8). NTpro-BNP levels drawn at the beginning of the dialysis session achieved a poor diagnostic accuracy for the detection of myocardial stunning (area under the ROC curve 0.61, 95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the exclusion of myocardial stunning at any time point. In logistic regression analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95% CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial stunning at any time point. CONCLUSION: Predialytic NTpro-BNP levels fail to adequately diagnose current dialysis-induced myocardial stunning, but help to identify patients with a propensity to develop dialysis-induced myocardial stunning at any time during the next 12 months.

Are there neurological consequences of recurrent intradialytic hypotension?

Structural abnormalities of the brain are common in hemodialysis (HD) patients, as are a wide range of severe functional deficiencies of cerebral function. Both depression and increasing dependency are highly prevalent in HD patients and worsen severely within the first 12 months of dialysis initiation. HD, as it is commonly practiced, is associated with significant recurrent episodes of circulatory stress. This results in acute injury to the heart, skin, kidney and gut, and drives longer term end-organ chronic injury. This article aims to explore the hypothesis that the cerebral microcirculation is also sensitive to dialysis-based circulatory stress (and other multiorgan consequences of recurrent dialysis-induced ischemia), and that this may drive specific patterns of brain injury with resultant psychiatric and functional consequences.

Rationale and design of a multi-centre randomised controlled trial of individualised cooled dialysate to prevent left ventricular systolic dysfunction in haemodialysis patients.

BACKGROUND: The main hypothesis of this study is that patients having regular conventional haemodialysis (HD) will have a smaller decline in cardiac systolic function by using cooler dialysate. Cooler dialysate may also be beneficial for brain function. METHODS/DESIGN: The trial is a multicentre, prospective, randomised, un-blinded, controlled trial. Patients will be randomised 1:1 to use a dialysate temperature of 37°C for 12 months or an individualised cooled dialysate. The latter will be set at 0.5°C less than the patient's own temperature, determined from the mean of 6 prior treatment sessions with a tympanic thermometer, up to a maximum of 36°C. Protocol adherence will be regularly checked. Inclusion criteria are incident adult HD patients within 180 days of commencing in-centre treatment 3 times per week with capacity to consent for the trial and without contra-indications for magnetic resonance imaging. Exclusion criteria include not meeting inclusion criteria, inability to tolerate magnetic resonance imaging and New York Heart Association Grade IV heart failure. During the study period, resting cardiac and cerebral magnetic resonance imaging will be performed at baseline and 12 months on an inter-dialytic day. Cardiovascular performance during HD will also be assessed by continuous cardiac output monitors, intra-dialytic echocardiography and biomarkers at baseline and 12 months. The primary outcome measure is a 5% between-group difference in left ventricular ejection fraction measured by cardiac magnetic resonance imaging at 12 months compared to baseline. Analysis will be by intention-to-treat. Secondary outcome measures will include changes in cerebral microstructure and changes in cardiovascular performance during HD. A total of 73 patients have been recruited into the trial from four UK centres. The trial is funded by a Research for Patient Benefit Grant from the National Institute of Healthcare Research. AO is funded by a British Heart Foundation Clinical Research Training Fellowship Grant. The funders had no role in the design of the study. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysate temperature for preserving cardiac and cerebral function in HD patients. TRIAL REGISTRATION: ISRCTN00206012 and UKCRN ID 7422.

Randomized Controlled Trial of Individualized Dialysate Cooling for Cardiac Protection in Hemodialysis Patients.

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°C±0.3°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(-1); 95% confidence interval, 0.02 to 0.34 s(-1)). 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(-1)×10(-3); 95% confidence interval, 0.1 to 3.6 mmHg(-1)×10(-3)). There were no intervention-related withdrawals or adverse events. CONCLUSIONS: In patients new to HD, individualized cooled dialysate did not alter the primary outcome but was well tolerated and slowed the progression of HD-associated cardiomyopathy. Because cooler dialysate is universally applicable at no cost, the intervention warrants wider adoption or confirmation of these findings in a larger trial.

Troponin T for the detection of dialysis-induced myocardial stunning in hemodialysis patients.

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.

Case report of ecstasy-induced renal venous thrombosis.

The use of 3,4-methylenedioxymethamphetamine, also known as MDMA or ecstasy, has been associated with vascular and end-organ damage. This case report describes, with histological evidence, the development renal venous thrombosis presenting with acute kidney injury following oral ingestion of 3,4-methylenedioxymethamphetamine (ecstasy).