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.

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.

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio-incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom.

Introduction: Intermittent renal replacement therapy induces cardiac stunning in chronic hemodialysis and acute kidney injury (AKI) patients. In chronic hemodialysis, recurrent stunning contributes to heart failure and cardiac death, with ultrafiltration and intradialytic hypotension being the principal determinants of this injury. Continuous renal replacement therapy (CRRT), with its lower ultrafiltration rates and improved hemodynamic profile, should protect against cardiac stunning in AKI. The objective of this study was to assess whether CRRT is associated with cardiac stunning in critically ill patients with AKI. Methods: We prospectively measured cardiac function using global and segmental longitudinal left ventricular strain using transthoracic echocardiography in 11 critically ill patients who were started on CRRT for AKI. We compared measurements at 4, 8, and 24 hours to baseline immediately prior to initiation of CRRT, with each patient serving as their own control. We also recorded blood pressure, heart rate, dose of vasoactive medications and intensive care unit mortality. Findings: Ten of 11 patients developed new regional cardiac stunning, with 8/11 within 4 hours of starting CRRT, despite stable hemodynamics. The number of affected left ventricular segments varied from 1 to 11 (out of 12). The stunning occurred both in patients with preserved and impaired baseline cardiac function, and 7/11 patients died in the intensive care unit. Discussion: Initiation of CRRT in critically ill patients with AKI is associated with cardiac stunning despite stable hemodynamics. This mechanism may explain lack of clinical benefit of CRRT over intermittent modalities and warrants further investigation to improve cardiovascular outcomes in critically ill patients with AKI.

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Background: Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23 Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. Methods: We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23 Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. Results: There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23–37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22–35] mmol/L), P =0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19–26] mmol/L), P =0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P =0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium ( P =0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% ( P =0.03). Conclusions: We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23 Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03004547.

Correspondence D versus [137] D (C) median skin sodium content is significantly higher, with (D) no significant difference in muscle sodium content. Correlation with BP of (E) skin and (F) muscle sodium content. Gray circle, [137] D ; black diamond, [140] D .

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status.