Non-invasive intradialytic percutaneous perfusion monitoring: a view to the heart through the skin.

Introduction: The life-sustaining treatment of hemodialysis (HD) induces recurrent and cumulative systemic circulatory stress resulting in cardiovascular injury. These recurrent insults compound preexisting cardiovascular sequalae leading to the development of myocardial injury and resulting in extremely high morbidity/mortality. This is largely a consequence of challenged microcirculatory flow within the myocardium (evidenced by detailed imaging-based studies). Currently, monitoring during HD is performed at the macrovascular level. Non-invasive monitoring of organ perfusion would allow the detection and therapeutic amelioration of this pathophysiological response to HD. Non-invasive percutaneous perfusion monitoring of the skin (using photoplethysmography-PPG) has been shown to be predictive of HD-induced myocardial stunning (a consequence of segmental ischemia). In this study, we extended these observations to include a dynamic assessment of skin perfusion during HD compared with directly measured myocardial perfusion during dialysis and cardiac contractile function. Methods: We evaluated the intradialytic microcirculatory response in 12 patients receiving conventional HD treatments using continuous percutaneous perfusion monitoring throughout HD. Cardiac echocardiography was performed prior to the initiation of HD, and again at peak-HD stress, to assess the development of regional wall motion abnormalities (RWMAs). Myocardial perfusion imaging was obtained at the same timepoints (pre-HD and peak-HD stress), utilizing intravenous administered contrast and a computerized tomography (CT)-based method. Intradialytic changes in pulse strength (derived from PPG) were compared with the development of HD-induced RWMAs (indicative of myocardial stunning) and changes in myocardial perfusion. Results: We found an association between the lowest pulse strength reduction (PPG) and the development of RWMAs (p = 0.03) and also with changes in global myocardial perfusion (CT) (p = 0.05). Ultrafiltration rate (mL/kg/hour) was a significant driver of HD-induced circulatory stress [(associated with the greatest pulse strength reduction (p = 0.01), a reduction in global myocardial perfusion (p = 0.001), and the development of RWMAs (p = 0.03)]. Discussion: Percutaneous perfusion monitoring using PPG is a useful method of assessing intradialytic hemodynamic stability and HD-induced circulatory stress. The information generated at the microcirculatory level of the skin is reflective of direct measures of myocardial perfusion and the development of HD-induced myocardial stunning. This approach for the detection and management of HD-induced cardiac injury warrants additional evaluation.

Hemodialysis-Related Acute Brain Injury Demonstrated by Application of Intradialytic Magnetic Resonance Imaging and Spectroscopy.

SIGNIFICANCE STATEMENT: Hemodialysis (HD) results in reduced brain blood flow, and HD-related circulatory stress and regional ischemia are associated with brain injury over time. However, studies to date have not provided definitive direct evidence of acute brain injury during a HD treatment session. Using intradialytic magnetic resonance imaging (MRI) and spectroscopy to examine HD-associated changes in brain structure and neurochemistry, the authors found that multiple white (WM) tracts had diffusion imaging changes characteristic of cytotoxic edema, a consequence of ischemic insult and a precursor to fixed structural WM injury. Spectroscopy showed decreases in prefrontal N -acetyl aspartate (NAA) and choline concentrations consistent with energy deficit and perfusion anomaly. This suggests that one HD session can cause brain injury and that studies of interventions that mitigate this treatment's effects on the brain are warranted. BACKGROUND: Hemodialysis (HD) treatment-related hemodynamic stress results in recurrent ischemic injury to organs such as the heart and brain. Short-term reduction in brain blood flow and long-term white matter changes have been reported, but the basis of HD-induced brain injury is neither well-recognized nor understood, although progressive cognitive impairment is common. METHODS: We used neurocognitive assessments, intradialytic anatomical magnetic resonance imaging, diffusion tensor imaging, and proton magnetic resonance spectroscopy to examine the nature of acute HD-associated brain injury and associated changes in brain structure and neurochemistry relevant to ischemia. Data acquired before HD and during the last 60 minutes of HD (during maximal circulatory stress) were analyzed to assess the acute effects of HD on the brain. RESULTS: We studied 17 patients (mean age 63±13 years; 58.8% were male, 76.5% were White, 17.6% were Black, and 5.9% were of Indigenous ethnicity). We found intradialytic changes, including the development of multiple regions of white matter exhibiting increased fractional anisotropy with associated decreases in mean diffusivity and radial diffusivity-characteristic features of cytotoxic edema (with increase in global brain volumes). We also observed decreases in proton magnetic resonance spectroscopy-measured N -acetyl aspartate and choline concentrations during HD, indicative of regional ischemia. CONCLUSIONS: This study demonstrates for the first time that significant intradialytic changes in brain tissue volume, diffusion metrics, and brain metabolite concentrations consistent with ischemic injury occur in a single dialysis session. These findings raise the possibility that HD might have long-term neurological consequences. Further study is needed to establish an association between intradialytic magnetic resonance imaging findings of brain injury and cognitive impairment and to understand the chronic effects of HD-induced brain injury. CLINICAL TRIALS INFORMATION: NCT03342183 .

Assessment of microcirculatory function during hemodialysis.

PURPOSE OF REVIEW: Patients with chronic kidney disease characteristically exhibit microcirculatory dysfunction, in combination with vascular damage. Hemodialysis superimposes additional circulatory stress to the microvasculature (repetitive ischemic insults/cumulative damage) resulting in high mortality. Intradialytic monitoring and hemodialysis delivery is currently limited to macrovascular/systemic assessment and detection of intradialytic systemic hypotension. Monitoring of the microcirculation has the potential to provide valuable information on hemodialysis-induced circulatory stress likely to result in end-organ ischemia (with/without systemic hypotension) generating an opportunity to intervene before tissue injury occurs. RECENT FINDINGS: Various noninvasive technologies have been used assessing the microcirculation in hemodialysis patients at rest. Some technologies have also been applied during hemodialysis studying the effects of treatment on the microcirculation. Despite the approach used, results are consistent. Hemodialysis patients have impaired microcirculations with treatment adding additional stress to inadequately regulated vascular beds. Utility/practicality/clinical relevance vary significantly between methodologies. SUMMARY: Intradialytic monitoring of the microcirculation can provide additional insights into a patient's individual response to treatment. However, this valuable perspective has not been adopted into clinical practice. A microcirculatory view could provide a window of opportunity to enable a precision medicine approach to treatment delivery improving current woefully poor subjective and objective clinical outcomes.

Impact of Expanded Hemodialysis Using Medium Cut-off Dialyzer on Quality of Life: Application of Dynamic Patient-Reported Outcome Measurement Tool.

RATIONALE & OBJECTIVE: Current hemodialysis (HD) treatments have limited ability to clear larger-molecular-weight uremic toxins. Retention is associated with increased symptom burden, low health-related quality of life (HRQoL), and high mortality. Improved clearance, using novel medium cut-off dialyzers, termed expanded HD (HDx), may be associated with improved subjective experience. We have previously developed a dynamic patient-reported outcome measure (PROM) instrument to allow iterative recording to better appreciate the overall burden of disease and assess the impact of therapy changes. STUDY DESIGN: Single-center interventional pilot study. SETTING & PARTICIPANTS: 28 patients established on maintenance HD, London, Ontario, Canada. INTERVENTION: Initial study consisting of 2-week observation (baseline-conventional high-flux HD) followed by 12 weeks of HDx. HRQoL was assessed using the dynamic PROM instrument thrice weekly (enabled in a dedicated app as the London Evaluation of Illness [LEVIL]). Extension phase; 2-week baseline with 24 weeks of HDx and 8-week washout. OUTCOMES: Principal aim was to establish whether HDx therapy was associated with improved HRQoL, evidence of dose-dependant response, and whether effects were durable over time, using LEVIL. RESULTS: Patients with lower LEVIL scores (<70/100) at baseline showed improvement in overall HRQoL after 8 weeks of therapy with similar carryover effect. General well-being, energy, and sleep quality were improved significantly as a consequence of HDx therapy. There were no detrimental effects of HDx detected in patients with higher baseline HRQoL. LIMITATIONS: Small nonrandomized sample size. The coronavirus disease 2019 pandemic interfered with the extension phase. CONCLUSIONS: Dynamic PROM assessment effectively identified patients with lower HRQoL and higher symptom burden, demonstrating durable time/dose-dependent improvements across a range of symptom domains. The use of this instrument may allow targeted selection of patients most likely to benefit from HDx therapy and assist in monitoring response and defining effect size and treatment duration to allow optimal design of further definitive randomized controlled trials of this newly introduced technology. FUNDING: Baxter Healthcare Canada. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03640858.

Pruritus: Is there a grain of salty truth?

Hemodialysis patients characteristically suffer from a range of unpleasant symptoms. Uremic pruritus effects close to half of the chronic kidney disease population, reducing quality of life and associated with increased mortality. Its pathophysiology though is poorly understood; currently deployed therapeutic approaches are ineffective. Excessive levels of skin and soft tissue sodium accumulate in dialysis patients, producing a range of biological consequences, including inflammation. We report an index case of a hemodialysis patient with debilitating pruritus and extreme levels of tissue sodium, measured with Sodium-23 magnetic resonance imaging. Both the tissue sodium loading and pruritus responded fully to initiation of expanded hemodialysis therapy with a recently introduced medium cutoff dialysis membrane-based dialyzer.

Intradialytic exercise preconditioning: an exploratory study on the effect on myocardial stunning.

BACKGROUND: Exercise preconditioning provides immediate protection against cardiac ischemia in clinical/preclinical studies in subjects without chronic kidney disease. In individuals requiring renal replacement therapy, hemodialysis (HD) results in significant circulatory stress, causing acute ischemia with resultant recurrent and cumulative cardiac injury (myocardial stunning). Intradialytic exercise (IDE) has been utilized to improve functional status in individuals receiving HD. The objective of this study was to explore the role of IDE as a preconditioning intervention and assess its effect on HD-induced myocardial stunning. METHODS: We performed a single-center cross-sectional exploratory study in adults on chronic HD participating in a clinical IDE program. HD-induced cardiac stunning was evaluated over two HD sessions within the same week: a control visit (no exercise) and an exposure visit (usual intradialytic cycling). Echocardiography was performed at the same three time points for each visit. Longitudinal strain values for 12 left ventricular segments were generated using speckle-tracking software to assess the presence of HD-induced regional wall motion abnormalities (RWMAs), defined as a ≥20% reduction in strain; two or more RWMAs represent myocardial stunning. RESULTS: A total of 19 patients were analyzed (mean age 57.2 ± 11.8 years, median dialysis vintage 3.8 years). The mean number of RWMAs during the control visit was 4.5 ± 2.6, falling to 3.6 ± 2.7 when incorporating IDE (a reduction of -0.95 ± 2.9; P = 0.17). At peak HD stress, the mean number of RWMAs was 5.8 ± 2.7 in the control visit versus 4.0 ± 1.8 during the exposure visit (a reduction of -1.8 ± 2.8; P = 0.01). CONCLUSION: We demonstrated for the first time that IDE is associated with a significant reduction in HD-induced acute cardiac injury.

Percutaneous perfusion monitoring for the detection of hemodialysis induced cardiovascular injury.

INTRODUCTION: The safe delivery of hemodialysis (HD) faces dual challenges; the accurate detection of systemic circulatory stress producing cardiovascular (CV) injury, and the ability to enable effective preemptive intervention for such injury. We performed a pilot study to examine the capability of a new noninvasive, real-time monitoring system to detect the deleterious effects of HD on CV stability. METHODS: Eight patients were evaluated with echocardiography prior to the initiation of HD and again at peak HD stress. Continuous CV physiologic monitoring was performed throughout using oximeter-based pulse waveform analysis (CVInsight® Monitoring System, Intelomed, Inc., Warrendale, PA, USA). Longitudinal strain (LS) values for 12 left ventricular segments were generated using speckle-tracking software (EchoPac, GE), to assess the presence of HD-induced regional wall motion abnormalities (RWMA), indicative of myocardial stunning. FINDINGS: A reduction in pulse strength (PS) of ≥40% detected by CVI was associated with the development of RWMA (P = 0.005). This reduction occurred in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no significant reduction in PS nor evidence of myocardial stunning. In subjects with cardiac stunning, the decrease in PS was evident early during HD, 11.49 ± 10 minutes into HD treatment, prior to the detection of RWMA, which were assessed at peak HD stress, mean 210 ± 16.43 minutes into HD treatment. DISCUSSION: Percutaneous perfusion monitoring, using pulse wave analysis, appears to be useful in identifying circulatory stress during HD and predicting the development of HD-induced myocardial stunning with a lead time long enough to consider timely intervention.