Update on Hemodialysis-Induced Multiorgan Ischemia: Brains and Beyond.

Hemodialysis is a life-saving treatment for patients with kidney failure. However, patients requiring hemodialysis have a 10-20 times higher risk of cardiovascular morbidity and mortality than that of the general population. Patients encounter complications such as episodic intradialytic hypotension, abnormal perfusion to critical organs (heart, brain, liver, and kidney), and damage to vulnerable vascular beds. Recurrent conventional hemodialysis exposes patients to multiple episodes of circulatory stress, exacerbating and being aggravated by microvascular endothelial dysfunction. This promulgates progressive injury that leads to irreversible multiorgan injury and the well-documented higher incidence of cardiovascular disease and premature death. This review aims to examine the underlying pathophysiology of hemodialysis-related vascular injury and consider a range of therapeutic approaches to improving outcomes set within this evolved rubric.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

Redefining the concept of residual renal function with kidney sodium MRI: a pilot study.

RATIONALE & OBJECTIVE: The concept of residual kidney function (RKF) is exclusively based upon urine volume and small solute clearance, making RKF challenging to assess in clinical practice. The aim of this study was to test the technical feasibility of obtaining useable 23Na-MRI kidney images in hemodialysis (HD) participants. STUDY DESIGN: We conducted an exploratory prospective study to quantify the cortico-medullary sodium gradient in healthy and HD participants. Participants fasted for eight hours prior to their study visit. Urine samples were collected to measure urinary osmolarity, before MRI. Proton and sodium pictures were merged; ROIs were delineated for the medulla and cortex when feasible. In cases where cortex could not be identified, we considered the cortico to medulla gradient (CMG) to be no longer present, resulting in a medulla-to-cortex ratio of 1. SETTING & PARTICIPANTS: 17 healthy volunteers and 21 HD participants. FINDINGS: Median (IQR) fasting medulla to cortex ratio was significantly higher 1.56 [1.5-1.61] in healthy volunteers compared to HD patients 1.22 [1.13-1.3], p < 0.0001. Medulla to cortex ratio and median urinary osmolarity were correlated (r = 0.87, p < 0.0001) in the whole population. We found a significant association between HD vintage and medulla to cortex ratio whereas we did not find any association with urine volume. Sodium signal intensity distribution within healthy kidney describes two different peaks- relating to well defined cortex and medulla; whereas HD participants displays only a single peak indicative of the markedly lower sodium concentration. LIMITATIONS: This study is only an exploratory study with a modest number of patients. CONCLUSIONS: the application of kidney sodium MRI to the study of RKF in patients receiving maintenance HD is practical and provides a previously unavailable ability to interrogate the function of remnant tubular function.

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 .

Effects of pediatric chronic kidney disease and its etiology on tissue sodium concentration: a pilot study.

BACKGROUND: Sodium-23 magnetic resonance imaging (23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na+] compared to healthy controls. METHODS: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg 23Na MRI for tissue [Na+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na+] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na+] and kidney function. RESULTS: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na+] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na+] Z-scores. Reduced whole-leg [Na+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na+] measures were significantly associated with proteinuria and hypoalbuminemia. CONCLUSIONS: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na+] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effects of the pandemic on adolescent and caregiver attitudes towards telemedicine use.

BACKGROUND: Telemedicine use increased during the COVID-19 pandemic. We compared both adolescent/caregiver attitudes towards telemedicine pre- and intra-pandemic. MATERIALS AND METHODS: In a tertiary care setting with a large remote catchment area, we conducted qualitative analysis of structured interviews with dyads of 11 to 18-year-old patients and their caregivers using NVivo during the pandemic and compared the findings to our previous research [1]. RESULTS: We enrolled 14 dyads (35 ± 27 in-person visits and 4 ± 3 telemedicine visits per participant) and compared these with 11 dyads before the pandemic. Adolescents' mean age was 15.2 ± 2.1 years (range 11.2 - 18.2). The median distance to our medical center was 184.8 km (range 3.9 - 1,214 km, 6 dyads > 100 km). While the preferred ratio of telemedicine to in-person visits was 2 : 1 in caregivers (like pre-pandemic), many emphasized telemedicine as the safer option. Interestingly, adolescents preferred more in-person visits during the pandemic (1 : 1 ratio) compared to pre-pandemic (2 : 1 ratio). Qualitative analysis identified two main themes: consultation-specific factors and contextual factors. Consultation-specific factors were more valued during in-person visits, especially by adolescents. Consultation-specific factors remained the same pre- and post-pandemic, however, adolescents more often emphasized comfort, communication, and personal connection for in-person visits during the pandemic. Contextual factors were valued for telemedicine by adolescents and caregivers, and telemedicine was identified as the norm during the pandemic. Interestingly, the two main contextual themes pre-pandemic: frustration with technological aspects of telemedicine and adolescents not taking telemedicine seriously, disappeared during the pandemic. No disadvantages for telemedicine in the contextual factors were identified during the pandemic. CONCLUSION: The COVID-19 pandemic changed the user-expressed attitudes (especially among adolescents) on the transfer to telemedicine for chronic care.

Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys.

Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups (r2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 (P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Laustsen and Bøgh in this issue.

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.

Addressing feasibility challenges to delivering intradialytic exercise interventions: a theory-informed qualitative study.

BACKGROUND: Intradialytic exercise (IDE) may improve physical function and health-related quality of life. However, incorporating IDE into standard hemodialysis care has been slow due to feasibility challenges. We conducted a multicenter qualitative feasibility study to identify potential barriers and enablers to IDE and generate potential solutions to these factors. METHODS: We conducted 43 semistructured interviews with healthcare providers and patients across 12 hospitals in Ontario, Canada. We used the Theoretical Domains Framework and directed content analysis to analyze the data. RESULTS: We identified eight relevant domains (knowledge, skills, beliefs about consequences, beliefs about capabilities, environmental context and resources, goals, social/professional role and identity, and social influences) represented by three overarching categories: knowledge, skills and expectations: lack of staff expertise to oversee exercise, uncertainty regarding exercise risks, benefits and patient interest, lack of knowledge regarding exercise eligibility; human, material and logistical resources: staff concerns regarding workload, perception that exercise professionals should supervise IDE, space, equipment and scheduling conflict concerns; and social dynamics of the unit: local champions and patient stories contribute to IDE sustainability. We developed a list of actionable solutions by mapping barriers and enablers to behavior change techniques. We also developed a feasibility checklist of 47 questions identifying key factors to address prior to IDE launch. CONCLUSIONS: Evidence-based solutions to identified barriers to and enablers of IDE and a feasibility checklist may help recruit and support units, staff and patients and address key challenges to the delivery of IDE in diverse clinical and research settings.

Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

BACKGROUND: Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care. METHODS: A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device. RESULTS: 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation). CONCLUSIONS: We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.

Management of severe polyuria in idiopathic Fanconi syndrome.

BACKGROUND: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. CASE-DIAGNOSIS/TREATMENT: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. CONCLUSIONS: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

Principles responsible for trace element concentrations in chronic kidney disease.

Derangements of trace elements often occur in patients with renal failure and play a crucial role in chronic kidney disease. The natural history of trace element deposition with worsening chronic kidney disease has been poorly described. Some essential trace elements may get wasted (e.g., selenium, zinc, and manganese) while other trace elements accumulate (e.g., cobalt, lead, molybdenum, and vanadium). Data are most readily available relating to hemodialysis patients. Continuous renal replacement therapies (for the treatment of acute kidney injury) and chronic kidney disease patients without need for renal replacement therapy remain largely unstudied. We have synthesized all available data on mode of absorption and elimination, volume of distribution, plasma protein binding, and proteinuria to summarize the existing literature, identify future areas of research and to allow some prediction of the fate of individual trace elements in clinical scenarios where no direct observational data are available. More prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required to improve how robust the current international guideline recommendations (KDOQI) are with respect to trace element monitoring.

Natural History of Cognitive Impairment in Critical Illness Survivors. A Systematic Review.

Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51-57%] vs. 35% [95% CI, 29-41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38-100%] vs. 36% [95% CI, 15-63%]; 12 months after ICU discharge: 43% [95% CI, 10-78%] vs. 18% [95% CI, 10-20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78-86%] vs. 48% [95% CI, 44-52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.

Adolescent and caregiver attitudes towards telemedicine use in pediatric nephrology.

BACKGROUND: Telemedicine is increasingly utilized as an alternative to in person consultation. Current pandemic conditions are providing additional impetus to virtual care delivery. We compared both adolescent and caregiver (parent or guardian) attitudes towards telemedicine (here as tertiary center to remote health care location) as a crucial determinant of longer-term effectiveness. METHODS: This qualitative research study analyzed transcribed structured telephone interviews with both 11-18 year-old pediatric nephrology patients and their caregivers and performed a quantitative analysis of patient demographics, disease factors and distance to tertiary center vs. telemedicine center. RESULTS: The study was conducted in a medium-sized tertiary pediatric nephrology centre with a large catchment area of over 0.5 million square kilometers and 629,000 children and adolescents under 18 years of age. Eleven dyads of adolescents and caregivers were enrolled. Five adolescents were male. The mean age of the adolescents was 14.4 ± 2.5 years (range 11.2-18.0). The median distance to our tertiary center was 191 km (range 110-1378 km). Four adolescents lived more than 500 km from our tertiary center. The 11 adolescents had a total of 334 in person visits (mean 30 ± 25) and 86 telemedicine visits (mean 8 ± 7). A ratio of 2:1 telemedicine to in-person visits was favored; with caregivers more in favor of remote care than adolescents. Qualitative analysis found that experiences with telemedicine were distinguished by consultation-specific factors and contextual factors. Contextual factors (travel/cost savings) were valued for telemedicine by adolescents and caregivers. Consultation-specific factors, such as the ability to show the doctor physical symptoms, were more valued during in-person consultations, especially by adolescents. The overall visit type preference was related to the nature of the consultation. For regular check-ups, and for adolescents with less complex needs, participants felt that telemedicine offered a comparable experience to in-person visits. Adolescents with more complex conditions preferred in-person visits. CONCLUSIONS: Indiscriminate transfer to chronic care predicated on mainly telemedicine approach is not compatible with user expressed attitudes (especially among adolescents). Accurately mapping models of care to these attitudes is an essential determinant of effective management and longer-term engagement with potentially life-long health challenges.

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study.

BACKGROUND: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3. METHODS AND FINDINGS: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification. CONCLUSIONS: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.

Current and novel imaging techniques to evaluate myocardial dysfunction during hemodialysis.

PURPOSE OF REVIEW: Patients on hemodialysis have significantly higher rates of cardiovascular mortality resulting from a multitude of myocardial dysfunctions. Current imaging modalities allow independent assessment of cardiac morphology, contractile function, coronary arteries and cardiac perfusion. Techniques such as cardiac computed tomography (CT) imaging have been available for some time, but have not yet had widespread adoption because of technical limitations related to cardiac motion, radiation exposure and safety of contrast agents in kidney disease. RECENT FINDINGS: Novel dynamic contrast-enhanced (DCE) CT imaging can be used to acquire high-resolution cardiac images, which simultaneously allow the assessment of coronary arteries and the quantitative measurement of myocardial perfusion. The advancement of recent CT scanners and cardiac protocols have allowed noninvasive imaging of the whole heart in a single imaging session with minimal cardiac motion artefact and exposure to radiation. SUMMARY: DCE-CT imaging in clinical practice would allow comprehensive evaluation of the structure, function, and hemodynamics of the heart in a short, well tolerated scanning session. It is an imaging tool enabling the study of myocardial dysfunction in dialysis patients, who have greater cardiovascular risk than nonrenal cardiovascular disease populations, both at rest and under cardiac stress associated with hemodialysis itself.

Tissue sodium concentrations in chronic kidney disease and dialysis patients by lower leg sodium-23 magnetic resonance imaging.

BACKGROUND: Sodium-23 magnetic resonance imaging (23Na MRI) allows direct measurement of tissue sodium concentrations. Current knowledge of skin, muscle and bone sodium concentrations in chronic kidney disease (CKD) and renal replacement therapy patients is limited. In this study we measured the tissue sodium concentrations in CKD, hemodialysis (HD) and peritoneal dialysis (PD) patients with 23Na MRI of the lower leg and explored their correlations with established clinical biomarkers. METHODS: Ten healthy controls, 12 CKD Stages 3-5, 13 HD and 10 PD patients underwent proton and 23Na MRI of the leg. The skin, soleus and tibia were segmented manually and tissue sodium concentrations were measured. Plasma and serum samples were collected from each subject and analyzed for routine clinical biomarkers. Tissue sodium concentrations were compared between groups and correlations with blood-based biomarkers were explored. RESULTS: Tissue sodium concentrations in the skin, soleus and tibia were higher in HD and PD patients compared with controls. Serum albumin showed a strong, negative correlation with soleus sodium concentrations in HD patients (r = -0.81, P < 0.01). Estimated glomerular filtration rate showed a negative correlation with tissue sodium concentrations (soleus: r = -0.58, P < 0.01; tibia: r = -0.53, P = 0.01) in merged control-CKD patients. Hemoglobin was negatively correlated with tissue sodium concentrations in CKD (soleus: r = -0.65, P = 0.02; tibia: r = -0.73, P < 0.01) and HD (skin: r = -0.60, P = 0.04; tibia: r = -0.76, P < 0.01). CONCLUSION: Tissue sodium concentrations, measured by 23Na MRI, increase in HD and PD patients and may be associated with adverse metabolic effects in CKD and dialysis.

Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate Cooling.

BACKGROUND: Residual renal function (RRF) confers survival in patients with ESRD but declines after initiating hemodialysis. Previous research shows that dialysate cooling reduces hemodialysis-induced circulatory stress and protects the brain and heart from ischemic injury. Whether hemodialysis-induced circulatory stress affects renal perfusion, and if it can be ameliorated with dialysate cooling to potentially reduce RRF loss, is unknown. METHODS: We used renal computed tomography perfusion imaging to scan 29 patients undergoing continuous dialysis under standard (36.5°C dialysate temperature) conditions; we also scanned another 15 patients under both standard and cooled (35.0°C) conditions. Imaging was performed immediately before, 3 hours into, and 15 minutes after hemodialysis sessions. We used perfusion maps to quantify renal perfusion. To provide a reference to another organ vulnerable to hemodialysis-induced ischemic injury, we also used echocardiography to assess intradialytic myocardial stunning. RESULTS: During standard hemodialysis, renal perfusion decreased 18.4% (P<0.005) and correlated with myocardial injury (r=-0.33; P<0.05). During sessions with dialysis cooling, patients experienced a 10.6% decrease in perfusion (not significantly different from the decline with standard hemodialysis), and ten of the 15 patients showed improved or no effect on myocardial stunning. CONCLUSIONS: This study shows an acute decrease in renal perfusion during hemodialysis, a first step toward pathophysiologic characterization of hemodialysis-mediated RRF decline. Dialysate cooling ameliorated this decline but this effect did not reach statistical significance. Further study is needed to explore the potential of dialysate cooling as a therapeutic approach to slow RRF decline.

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here.

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.

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.