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.

Initial evaluation of extracorporeal immunomodulatory therapy for the treatment of critically ill COVID-19 infected patients.

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.

Non-Invasive Monitoring of Core Body Temperature for Targeted Temperature Management in Post-Cardiac Arrest Care.

Importance: Accurate monitoring of core body temperature is integral to targeted temperature management (TTM) following cardiac arrest. However, there are no reliable non-invasive methods for monitoring temperature during TTM. Objectives: We compared the accuracy and precision of a novel non-invasive Zero-Heat-Flux Thermometer (SpotOn™) to a standard invasive esophageal probe in a cohort of patients undergoing TTM post-cardiac arrest. Design Setting and Participants: We prospectively enrolled 20 patients undergoing post-cardiac arrest care in the intensive care units at the London Health Sciences Centre in London, Canada. A SpotOn™ probe was applied on each patient's forehead, while an esophageal temperature probe was inserted, and both temperature readings were recorded at 1-min intervals for the duration of TTM. Main outcomes and Measures: We compared the SpotOn™ and esophageal monitors using the Bland-Altman analysis and the Pearson correlation, with accuracy set as a primary outcome. Secondary outcomes included precision and correlation. Bias exceeding 0.1°C and limits of agreement exceeding 0.5°C were considered clinically important. Results: Sixteen (80%) of patients had complete data used in the final analysis. The median (interquartile range) duration of recording was 38 (12-56) h. Compared to the esophageal probe, SpotOn™ had a bias of 0.06 ± 0.45°C and 95% limits of agreement of -0.83 to 0.95°C. The Pearson correlation coefficient was 0.97 (95% confidence interval 0.9663-0.9678), with a two-tailed p < 0.0001. Conclusion and Relevance: The SpotOn™ is an accurate method that may enable non-invasive monitoring of core body temperature during TTM, although its precision is slightly worse than the predefined 0.5°C when compared to invasive esophageal probe.

Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia.

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH. Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model. Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (-14%, p = 0.03) at rest and after stress (-14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave. Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

Hemodialysis Patients Have Impaired Cerebrovascular Reactivity to CO2 Compared to Chronic Kidney Disease Patients and Healthy Controls: A Pilot Study.

INTRODUCTION: Recurrent hemodialysis (HD)-induced ischemia has emerged as a mechanism responsible for cognitive impairment in HD patients. Impairment of cerebrovascular function in HD patients may render the brain vulnerable to HD-induced ischemic injury. Cerebrovascular reactivity to CO2 (CVR) is a noninvasive marker of cerebrovascular function. Whether CVR is impaired in HD patients is unknown. In this study, we compared CVR between healthy participants, HD patients, and chronic kidney disease (CKD) patients not yet requiring dialysis. METHODS: This was a single-center prospective observational study carried out at Kidney Clinical Research Unit in London, Canada. We used carefully controlled hypercapnia to interrogate brain vasomotor control. Transcranial Doppler was combined with 10-mm Hg step changes in CO2 from baseline to hypercapnia (intervention) and back to baseline (recovery) to assess CVR in 8 HD, 10 CKD, and 17 heathy participants. RESULTS: HD patients had lower CVR than CKD or healthy participants during both intervention and recovery (P < 0.0001). There were no differences in CVR between healthy and CKD participants during either intervention (P = 0.88) or recovery (P = 0.99). The impaired CVR in HD patients was independent of CO2-induced changes in blood pressure, heart rate, cardiac output, or dialysis vintage. In the CKD group, CVR was not associated with the estimated glomerular filtration rate. CONCLUSIONS: Our study shows that HD patients have impaired CVR relative to CKD and healthy participants. This renders HD patients vulnerable to ischemic injury during circulatory stress of dialysis and may contribute to the pathogenesis of cognitive impairment.