Application of the Lomb-Scargle Periodogram to InvestigateHeart Rate Variability during Haemodialysis.

Short-term cardiovascular compensatory responses to perturbations in the circulatory system caused by haemodialysis can be investigated by the spectral analysis of heart rate variability, thus providing an important variable for categorising individual patients' response, leading to a more personalised treatment. This is typically accomplished by resampling the irregular heart rate to generate an equidistant time series prior to spectral analysis, but resampling can further distort the data series whose interpretation can already be compromised by the presence of artefacts. The Lomb-Scargle periodogram provides a more direct method of spectral analysis as this method is specifically designed for large, irregularly sampled, and noisy datasets such as those obtained in clinical settings. However, guidelines for preprocessing patient data have been established in combination with equidistant time-series methods and their validity when used in combination with the Lomb-Scargle approach is missing from literature. This paper examines the effect of common preprocessing methods on the Lomb-Scargle power spectral density estimate using both real and synthetic heart rate data and will show that many common techniques for identifying and editing suspect data points, particularly interpolation and replacement, will distort the resulting power spectrum potentially misleading clinical interpretations of the results. Other methods are proposed and evaluated for use with the Lomb-Scargle approach leading to the main finding that suspicious data points should be excluded rather than edited, and where required, denoising of the heart rate signal can be reliably accomplished by empirical mode decomposition. Some additional methods were found to be particularly helpful when used in conjunction with the Lomb-Scargle periodogram, such as the use of a false alarm probability metric to establish whether spectral estimates are valid and help automate the assessment of valid heart rate records, potentially leading to greater use of this powerful technique in a clinical setting.

Brain white matter microstructure in end-stage kidney disease, cognitive impairment, and circulatory stress.

INTRODUCTION: Structural and functional brain white matter abnormalities are poorly characterized in patients with end-stage kidney disease. METHODS: We examined the prevalence of the brain white matter microstructure disruption using diffusion tensor magnetic resonance imaging and its association with hemodynamic performance and cognitive defects in 49 incident hemodialysis (HD) patients and compared these to 25 age-matched normal controls. We analyzed fractional anisotropy (FA) and mean diffusivity (MD) maps of the images, a voxelwise statistical analysis was done using tract-based spatial statistics. Hemodynamic assessment was done using extrema points analysis model of continuous blood pressure monitoring. FINDINGS: We found significant white matter damage in HD patients compared with normal controls (peak FA 0.471 ± 0.031 vs 0.486 ± 0.022 P = 0.023, peak MD 0.00194 ± 0.000363 10-3 mm2 .s-1 vs 0.00167 ± 0.0003 10-3 mm2 .s-1 P = 0.002). There was diffuse pattern of white matter damage in HD patients, which was independent of age, gender, and the presence of ischaemic heart disease and diabetes with significantly lower FA values in HD patients than normal controls (0.467 ± 0.037 vs 0.507 ± 0.026, P < 0.05 corrected for family wise error. HD patients had worse cognitive scores that correlated with white matter damage (for peak FA, Montreal cognitive assessment r = 0.478 P = 0.001, Trail A r = -0.486 P = 0.001, Trail B r = -0.464 P = 0.001; for peak MD, Montreal cognitive assessment r = -0.533 P < 0.001, Trail A r = 0.641 P < 0.001, Trail B r = 0.514 P < 0.001). In a multivariable linear regression analysis that included age, smoking, the presence of ischaemic heart disease, and diabetes mellitus, higher frequency of mean arterial blood pressure extrema points during HD was independently associated with white matter damage (ß = -0.296, P = 0.036, Adjusted R2 for the whole model = 0.400). DISCUSSION: End-stage kidney disease patients on HD have more brain white matter damage and cognitive impairment than age-matched controls that are linked to hemodynamic functional measures.

Randomized clinical trial of dialysate cooling and effects on brain white matter.

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=-0.439, 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.

Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment.

Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.

The reimbursement and cost of acute kidney injury: a UK hospital perspective.

BACKGROUND: Despite the great interest in acute kidney injury (AKI), there have been very few studies that examined the economic impact and costing methodologies of AKI. We aimed to examine the cost and income of AKI in hospitalised patients over a period of 1 year using the NHS costing system related to that year. METHODS: A total of 627 patients discharged between January 2008 and December 2008 with AKI were identified by International Classification of Disease 10 codes (ICD-10). Basic demographic data were collected using the hospital electronic records, and the severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) classification. We calculated the total income and isolated the AKI income related to AKI-specific finished consultant episodes. Then we conducted a patient level costing exercise using relative value units (RVU) to compare the cost of AKI to the actual income. RESULTS: The total spell income for all patients was GBP 1,954,922.7; the mean total income per patient was GBP 3,752.3 (95% CI 3,594.6-3,903.9). AKIN stage 3 generated significantly higher total spell and AKI income. The estimated overall cost of treating AKI was higher than the AKI income to the Primary Care Trust (GBP 1,984,543.9 vs. 1,755,395). CONCLUSION: AKIN stage 3 has a significant economic impact when compared with AKIN stages 1 and 2. The move towards a patient level costing using RVU could be a more efficient way to match cost and income.

Effects of arteriovenous fistula formation on arterial stiffness and cardiovascular performance and function.

BACKGROUND: Native arteriovenous fistula (AVF) is the vascular access of choice and its use cf. catheters is associated with sustained reduction in mortality. This may be due to factors beyond dialysis catheter-associated sepsis. This study aimed to investigate the impact of AVF formation on the spectrum of cardiovascular factors that might be important in the pathophysiology of cardiovascular diseases in chronic kidney disease (CKD) patients. METHODS: We recruited 43 pre-dialysis patients who underwent AVF formation. Patients were studied 2 weeks prior to AVF operation and 2 weeks and 3 months post-operatively. Haemodynamic variables were measured using pulse wave analysis, carotid femoral pulse wave velocity (CF-PWV) by applanation tonometry and AVF blood flow by Doppler ultrasound. Bioimpedence analysis was performed and patients underwent serial transthoracic echocardiography. RESULTS: AVF formation was successful in 30/43 patients. Two weeks post-operatively, total peripheral resistance decreased (-17 ± 18%, P = 0.001), stroke volume tended to rise (12 ± 30 mL, P = 0.053) and both heart rate (4 ± 8 bpm, P = 0.01) and cardiac output (1.1 ± 1.5 L/min, P = 0.001) increased. Systolic and diastolic blood pressures (BPs) reduced (-9 ± 18 mmHg; -9 ± 10 mmHg; ≤ P = 0.006) and CF-PWV reduced (-1.1 ± 1.5 m/s, P = 0.004). Left ventricular ejection fraction (LVEF) increased (6 ± 8%, P < 0.001). All the observed changes were largely maintained after 3 months. No change in hydration status/body composition was observed. CONCLUSIONS: AVF formation resulted in a sustained reduction in arterial stiffness and BP as well as an increase in LVEF. Overall, post-AVF adaptations might be characterized as potentially beneficial in these patients and supports the widespread use of native vascular access, including older or cardiovascular compromised individuals.

Cardiac assessment in chronic kidney disease.

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.