Extracellular Volume Overload Research Articles

Endothelin-1, Extracellular Volume Overload, and Hemodynamics in Hemodialysis Patients.

Extracellular volume (ECV) overload and endothelial cell dysfunction are mortality risk factors in hemodialysis (HD) patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in HD patients. We hypothesized there would be associations between ET-1 and ECV overload in hypertensive HD patients. We obtained pre-HD ET-1, ECV/weight (bioimpedance spectroscopy), pre-HD hemodynamics, and ambulatory blood pressure (BP) in an HD cohort. Following appropriate transformations, we conducted correlation and linear regression analyses idendifying associations between ET-1, ECV overload, total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP. Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/ml. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) l/kg, 3,161 (2,711-3,642) dynes × s/cm-5/m2, 2.92 (0.6) l/min/m2, and 143 (14) mm Hg, respectively. After reciprocal-transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r = 0.3, P = 0.01), log-transformed TPRI (r = -0.3, P = 0.006), CI (r = 0.3, P = 0.009), and ambulatory BP (r = -0.3, P = 0.02). These associations persisted in linear regression analysis (β = 0.15, P = 0.002; β = -0.8, P = 0.002; β = 0.2, P = 0.002; β = -19, P = 0.03). In hypertensive HD patients, ET-1 associates with ECV overload higher TPRI and ambulatory BP, and lower CI. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload.

Revisiting the concept of constant tissue conductivities for volume estimation in dialysis patients using bioimpedance spectroscopy

Current estimation of body fluid volumes in hemodialysis patients using bioimpedance analysis assumes constant specific electrical characteristics of biological tissues despite a large variation in plasma Na+ concentrations [Na+], ranging from 130 to 150 mmol/L. Here, we examined the potential effect of variable [Na+] on bioimpedance-derived volume overload. Volumes were calculated from published whole-body extra- and intracellular resistance data and relationships using either "standard" or "revised" specific electrical characteristics modeled as functions of [Na+]. With "standard" assumptions, volumes increased with increasing [Na+]. The increase in volume overload was about 0.5 dm3 and 3% of extracellular volume per 10 mmol/dm3 of [Na+] in a 75 kg patient. This increase was abolished when the same bioimpedance data were analyzed under "revised" conditions. The overestimation in extracellular volume overload in the range of 0.5 dm3 per 10 mmol/dm3 [Na+] perfectly matches the positive relationship determined in a large cohort of hemodialysis patients. The bias may be considered moderate when interpreting data of individual patients, but may become important when comparing data of larger patient groups. The bias disappears when analysis of bioimpedance data accounts for differences in tissue electrical properties, using individual [Na+].

Extracellular Volume Overload Is Associated With Increased Endothelin-1 in Hypertensive Hemodialysis Patients

Extracellular Volume Overload Is Associated With Increased Endothelin-1 in Hypertensive Hemodialysis Patients

The effects of extracellular volume and intradialytic peripheral resistance changes on ambulatory blood pressure in hemodialysis patients with and without recurrent intradialytic hypertension.

BackgroundHypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH).MethodsIn this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope.ResultsIn fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (β = 133, P = 0.01; n = 52) and ambulatory BP slope (β = −4.28, P = 0.03; n = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (β = 314, P = 0.0005; n = 16) and with ambulatory BP slope in those without recurrent IH (β = −4.56, P = 0.04; n = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses.ConclusionAmbulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.

Supine equilibration of extracellular fluid in peritoneal dialysis varies with intra-abdominal pressure.

Increased intra-abdominal pressure (PIA) leads to venous congestion in splanchnic and adjoining circulations. The aim is to examine whether PIA in peritoneal dialysis (PD) affects the mobilization of extracellular fluid from the lower body in supine body position. Patients were studied during a regular peritoneal equilibration test (PET) in supine body position using multifrequency bioimpedance analysis to determine extracellular resistance and absolute volume overload (AVO) in wrist-to-ankle (W2A) as well as in ankle-to-ankle (A2A) configurations. Measurements were taken at baseline (T0) after draining the peritoneal cavity, at T1 shortly after filling with 2 L of standard dialysate, and at T2 before taking the 2 h PET samples. PIA was measured from the column height in the PD catheter. Extracellular resistance in the lower extremities (RL) was taken as half of the A2A resistance. Eighteen patients (56 ± 15 years, 76 ± 21 kg, body mass index (BMI) 26.4 ± 7 kg/m2, 13 men) were studied. After having assumed a supine body position for the duration of 17, 77, and 155 min, AVO continuously decreased from 1.6 ± 1.3 (T0) to 1.2 ± 1.5 (T1) and 1.0 ± 1.4 L (T2). RL significantly increased from 238 ± 57 (T0) to 254 ± 62 (T1) and 264 ± 67 Ohm (T2). This increase was negatively correlated to BMI and PIA measured at any time point, but not to net ultrafiltration volume. Orthostatic fluid shifts from the lower limbs may take up to 2 h in supine PD patients, especially with high BMI and PIA because of venous congestion in splanchnic and adjoining circulations.

The efficacy of managing fluid overload in chronic peritoneal dialysis patients by a structured nurse-led intervention protocol

BackgroundExtracellular volume overload is a common problem in peritoneal dialysis (PD) patients and is associated with excessive mortality. We determine the effectiveness of treating PD patients with extracellular volume overload by a structured nurse-led intervention program.MethodsThe hydration status of PD patients was screened by bioimpedance spectroscopy (BIS). Fluid overload was defined as overhydration volume ≥ 2 L. Patients were classified into Symptomatic and Asymptomatic Groups and were managed by a structured nurse-led intervention protocol that focused on education and motivation. Hypertonic cycles were given for short term symptom relief for the Symptomatic group. Patients were followed for 12 weeks for the change in volume status, blood pressure, knowledge and adherence as determined by standard questionnaires.ResultsWe recruited 103 patients (53 Symptomatic, 50 Asymptomatic Group. There was a significant reduction in overhydration volume 4 weeks after intervention, which was sustained by week 12; the overall reduction in overhydration volume was 0.96 ± 1.43 L at 4 weeks, and 1.06 ± 1.70 L at 12 weeks (p < 0.001 for both). The improvement was significant for both Symptomatic and Asymptomatic Groups. There was a concomitant reduction in systolic blood pressure in the Asymptomatic (146.9 ± 20.7 to 136.9 ± 19.5 mmHg, p = 0.037) but not Symptomatic group. The scores of knowledge, adherence to dietary control and advices on daily habit at week 4 were all significantly increased, and the improvement was sustained at week 12.ConclusionsThe structured nurse-led intervention protocol has a lasting benefit on the volume status of PD patients with extracellular volume overload. BIS screening allows prompt identification of volume overload in asymptomatic patients, and facilitates a focused effort on this high risk group.

Sodium loss, extracellular volume overload and hypertension in peritoneal dialysis patients treated by automated peritoneal dialysis cyclers.

Achieving sodium balance is important for peritoneal dialysis patients, as sodium excess may lead to hypertension and extracellular water expansion. We wished to determine whether greater sodium removal had adverse consequences. We calculated 24-h urinary and peritoneal sodium losses in peritoneal dialysis patients treated by automated cyclers, when attending for peritoneal membrane and bioimpedance assessments. We reviewed 439 peritoneal dialysis patients, 56.7% male, average age 54.6 years, median sodium loss 110 (68-155) mmol/day. Sodium loss was strongly associated with urine volume, r = 0.37, protein nitrogen appearance rate, r = 0.29, and body cell mass, r = 0.21, all p < 0.001. We found no association with blood pressure or anti-hypertensive medication prescription, or extracellular water. On multivariable logistic regression analysis, sodium loss was associated with greater urine output, odds ratio 1.001, 95% confidence interval 1.00-1.001, p < 0.001, and protein nitrogen appearance (odds ratio 1.023, confidence interval 1.006-1.04), p = 0.008. Adjusting for body weight, sodium loss was associated with urine output (odds ratio 1.001, confidence interval 1.001-1.002, p < 0.001), and negatively with body fat index (odds ratio 0.96, confidence interval 0.93-0.99, p = 0.008) and co-morbidity grade (odds ratio 0.58, confidence interval 0.36-0.39, p = 0.023). Heavier peritoneal dialysis patients with greater estimated dietary protein intake (protein nitrogen appearance), those with greater residual renal function and peritoneal clearances, along with lower co-morbidity, had greater daily sodium losses. Adjusting for body weight, then sodium losses were greater with higher daily urine output, and lower in patients with proportionately more body fat and co-morbidity. Sodium losses would appear to primarily determined by body size and not associated with hypertension or extracellular water expansion.

Bioimpedance vector analysis for the detection of extracellular volume overload and sarcopenia in systemic AL amyloidosis.

Bioimpedance vector analysis for the detection of extracellular volume overload and sarcopenia in systemic AL amyloidosis.

Assessing Extracellular Volume in Hemodialysis Patients Using Intradialytic Blood Pressure Slopes

Background/Aims: Extracellular volume (ECV) overload is a mortality risk factor in hemodialysis patients, but no standard approach exists to objectively assess this clinically. We aimed to quantify relationships between slopes of repeated intradialytic blood pressure (BP) measurements and ECV. Methods: In a cross-sectional study of 71 hemodialysis patients, we calculated BP slopes from all intradialytic measurements using Gaussian regression. We measured extracellular and total body water (TBW) with bioimpedance spectroscopy. We analyzed unconditional and conditional associations between BP slope and volume metrics with mixed linear models and sensitivity analyses using non-linear intradialytic BP trajectory. Results: Mean systolic intradialytic BP slope (IBPS) was –0.06 (0.1) mm Hg/min. Post-dialysis extracellular water (ECW)/weight was the volume metric mostly strongly associated with slope (r = 0.34, p = 0.007 for unconditional analysis; β = 1.45, p = 0.001 for conditional analysis). Among subjects with post-dialysis systolic BP ≥130 mm Hg, the association strengthened (r = 0.40, p = 0.006; β = 1.42, p = 0.003). ECV was more strongly associated with the BP slope than with pre-dialysis, post-dialysis, or delta systolic BP (r = –0.07, 0.19, 0.28; p = 0.6, 0.1, 0.03). In nonlinear models, BP trajectory also had the strongest association with post-dialysis ECW/body weight (p < 0.001). Conclusions: In hypertensive hemodialysis patients, measurements of ECV excess are more strongly associated with IBPSs than with pre-dialysis, post-dialysis, or change in systolic BP. Among varying volume metrics, post-dialysis ECW/weight has the strongest association with these slopes. Determining IBPS is a novel method to optimize clinical assessment of ECV in hemodialysis patients.

Special situations: Intradialytic hypertension/chronic hypertension and intradialytic hypotension.

Hypertension is a comorbidity that is present in the majority of end-stage renal disease patients on maintenance hemodialysis. This population is particularly unique because of the dynamic nature of blood pressure (BP) during dialysis. Modest BP decreases are expected in most hemodialysis patients, but intradialytic hypotension and intradialytic hypertension are two special situations that deviate from this as either an exaggerated or paradoxical response to the dialysis procedure. Both of these phenomena are particularly important because they are associated with increased mortality risk compared to patients with modest decreases in BP during dialysis. While the detailed pathophysiology is complex, intradialytic hypotension occurs more often in patients prescribed fast ultrafiltration rates, and reducing this rate is recommended in patients that regularly exhibit this pattern. Patients with intradialytic hypertension have a poorly explained increase in vascular resistance during dialysis, but the consistent associations with extracellular volume overload point toward more aggressive fluid management as the initial management choices for these patients. This up to date review provides the most recent evidence supporting these recommendations as well as the most up to date epidemiologic and mechanistic research studies that have added to this area of dialysis management.

Interplay of volume, blood pressure, organ ischemia, residual renal function, and diet: certainties and uncertainties with dialytic management.

Extracellular fluid volume overload and its inevitable consequence, hypertension, increases cardiovascular mortality in the long term by leading to left ventricular hypertrophy, heart failure, and ischemic heart disease in dialysis patients. Unlike antihypertensive medications, a strict volume control strategy provides optimal blood pressure control without need for antihypertensive drugs. However, utilization of this strategy has remained limited because of several factors, including the absence of a gold standard method to assess volume status, difficulties in reducing extracellular fluid volume, and safety concerns associated with reduction of extracellular volume. These include intradialytic hypotension; ischemia of heart, brain, and gut; loss of residual renal function; and vascular access thrombosis. Comprehensibly, physicians are hesitant to follow strict volume control policy because of these safety concerns. Current data, however, suggest that a high ultrafiltration rate rather than the reduction in excess volume is related to these complications. Restriction of dietary salt intake, increased frequency, and/or duration of hemodialysis sessions or addition of temporary extra sessions during the process of gradually reducing postdialysis body weight in conventional hemodialysis and discontinuation of antihypertensive medications may prevent these complications. We believe that even if an unwanted effect occurs while gradually reaching euvolemia, this is likely to be counterbalanced by favorable cardiovascular outcomes such as regression of left ventricular hypertrophy, prevention of heart failure, and, ultimately, cardiovascular mortality as a result of the eventual achievement of normal extracellular fluid volume and blood pressure over the long term.

Renal sodium avidity in heart failure: from pathophysiology to treatment strategies.

Increased neurohumoral stimulation resulting in excessive sodium avidity and extracellular volume overload are hallmark features of decompensated heart failure. Especially in case of concomitant renal dysfunction, the kidneys often fail to elicit effective natriuresis. While assessment of renal function is generally performed by measuring serum creatinine-a surrogate for glomerular filtration-, this only represents part of the nephron's function. Alterations in tubular sodium handling are at least equally important in the development of volume overload and congestion. Venous congestion and neurohumoral activation in advanced HF further promote renal sodium and water retention. Interestingly, early on, before clinical signs of heart failure are evident, intrinsic renal derangements already impair natriuresis. This clinical review discusses the importance of heart failure (HF) induced changes in different nephron segments. A better understanding of cardiorenal interactions which ultimately result in sodium avidity in HF might help to treat and prevent congestion in chronic and acute HF.

Evaluation and Treatment of Hypertension in End-Stage Renal Disease Patients on Hemodialysis.

Hypertension is one of the most common cardiovascular comorbidities in end-stage renal disease patients on hemodialysis. Its complex pathophysiology is related to extracellular volume overload, increased vascular resistance stemming from factors related to uremia or abnormal signaling from the failing kidneys, as well as the unique blood pressure changes that take place during and between hemodialysis treatments. Despite the changing nature of blood pressure over time in hemodialysis patients, hypertension diagnosed in or out of the hemodialysis unit is associated with increased cardiovascular morbidity and mortality. This review details the causes of hypertension in hemodialysis patients and provides an updated review of the clinical consequences and management of hypertension.

35 Body composition and volume distribution in normal and ypertensive pregnancies

Background Volume assessment in the pre-eclampsia is difficult. Intravascular volume contraction and oliguria in the face of extracellular volume overload and oedema appears to be accepted yet often difficult to manage. The relationship between clinically evident oedema and volume status is not clear. Aim To examine the distribution of fluid in normal and hypertensive pregnancies using a non-invasive technique. Methods Women in their 3rd trimester in a cross sectional study. There were five groups: normotensive pregnancy (NP); gestational hypertension (GH); essential hypertension (EH), pre-eclampsia (PE) and non-pregnant controls (C). Each study participant had their body composition, including total body water (TBW), intracellular volume (ICW) & extracellular volume (ECW) as well as over hydration (OH) measured using the Fresenius BCM®. Body Mass Index (BMI) was calculated and % fat mass measured using BCM. Results A total of 128 women have been recruited to date as follows; NP = 20 GH = 51, EH = 16, PE = 14 and C = 27. Download : Download high-res image (214KB) Download : Download full-size image Pregnant women had higher TBW and ECW than the control group (p 0.05). However amongst the pregnant women there was no difference in measured fluid in any of the compartments despite a trend in those with PE toward fluid overload. Hypertensive pregnant women were also bigger than their normotensive pregnant counterparts. Conclusion In this small cohort we were unable to find a clear difference in volume status among women with normotensive pregnancies, those with uncomplicated hypertensive disorders of pregnancy EH & GH or clinically evident PE. We were however able to determine that women with PE tended to be more over hydrated than women with other hypertensive disorders of pregnancy. Small numbers in this group may have impacted the power of this result however. Future studies combining this technique with non-invasive cardiac output monitoring could perhaps yield a more comprehensive fluid assessment in this challenging group of patients.

Extracellular Volume Overload and Increased Vasoconstriction in Patients With Recurrent Intradialytic Hypertension

Background/Aims: Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. Methods: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW) and extracellular water (ECW), as well as cardiac index (CI) and total peripheral resistance index (TPRI). Results: The ECW/TBW was 0.453 (0.05) pre-dialysis and 0.427 (0.04) post-dialysis in controls vs. 0.478 (0.03) and 0.461 (0.03) in IH patients (p=0.01 post-dialysis). The ECW/TBW change was -0.027 (0.03) in controls and -0.013 (0.02) in IH patients (p=0.1). In controls, pre- and post-dialysis TPRI were 3254 (994) and 2469 (529) dynes/sec/cm²/m² vs. 2983 (747) and 3408 (980) dynes/sec/cm²/m² in IH patients (p=0.002 post-dialysis). There were between-group differences in TPRI change (0=0.0001), but not CI (p=0.09). Conclusions: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.

Hypertension in Patients with Chronic Kidney Disease

The prevalence of hypertension in chronic kidney disease (CKD) patients exceeds that of the general population. Uncontrolled hypertension plays a significant role in progression to end stage renal disease and results in increased cardiovascular morbidity and mortality. A complex interplay between various pathophysiologic mechanisms is responsible for the development of hypertension in this patient population. The major factors being extracellular volume overload, increased endothelin-1 release and excess renin-angiotensin-aldosterone system and sympathetic nervous system activity. Dietary and lifestyle modifications have synergistic effects to drug therapy in the control of hypertension. There is no single blood pressure target that is optimal for all CKD patients. It is important to individualize the treatment depending on age, the severity of albuminuria, and comorbidities. Drugs blocking the renin-angiotensin-aldosterone system are the recommended first-line antihypertensive agents for most CKD patients. Intradialytic hypertension may be prevented by individualizing the dialysis prescription and using nondialyzable antihypertensives. New onset of hypertension in the elderly or new onset of difficult to control hypertension in a previously well controlled hypertensive patient should prompt the work up for atherosclerotic renal vascular disease.

P-043: Hypertension and end stage renal disease requiring hemodialysis

Background The prevalence of hypertension (HT) remains high in hemodialysis patients ranging from 55% to 85%. Its origins are in the extracellular volume overload associated to the increased arterial resistance. The aim of our study was to describe the epidemiological, clinical and therapeutic characteristics in our hypertensive hemodialysis population. Methods This was a cross-sectional descriptive study about 61 hemodialysis patients between May and August 2014. The collected data were age, type of initial renal disease, hemodialysis duration and treatment of HT. Results Of these 61 patients undergoing hemodialysis, 58 were hypertensive when hemodialysis was started, 49 were hypertensive since the discovery of the initial renal disease, and 45 patients required antihypertensive treatment after at least 6 months of hemodialysis at the end of the study. The average age of hypertensive patients was 56 years (22-88 years). 36 patients were males. The mean duration of renal replacement therapy was 7.9 years (1-31 years). In patients who started hemodialysis with HT, the initial nephropathy was a glomerulopathy in 23 cases, including 15 cases of diabetic nephropathy, vascular nephropathy in 13 cases, tubulointerstitial in 10 cases (including 2 cases of polycystic kidney disease) and in 10 cases renal disease was indeterminate. Sixty patients used at least one antihypertensive treatment during their followed in renal replacement. Seventeen hemodialysis patients had left ventricular hypertrophy and 4 had presented an ischemic stroke. Conclusions Hypertension in chronic hemodialysis patients is common. Hypertension is a risk factor for cardiovascular disease which is the main cause of morbidity and mortality in the dialysis population. The extra-cellular volume expansion is the main pathophysiological determinant of hypertension in dialysis patients. To manage hypertension, limiting dietary intake, and individualizing dialysate sodium delivery would be the first steps. Antihypertensive drug therapies can effectively reduce blood pressure and are needed by the vast majority of hemodialysis patients.

Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis

Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis

Predialysis NTproBNP Predicts Magnitude of Extracellular Volume Overload in Haemodialysis Patients

Introduction: Increased natriuretic peptides are associated with increased cardiovascular and all-cause mortality for haemodialysis (HD) patients. However, debate continues whether these biomarkers are increased by extracellular water (ECW) excess and can be used to aid clinical assessment of volume status and help determine target weight. Methods: We measured N terminal probrain natriuretic peptide (NT-proBNP) predialysis in 375 stable haemodialysis outpatients with corresponding pre and postdialysis multifrequency bioelectrical impedance assessments (MFBIA) of (ECW)/total body water (TBW). Results: Median age 64 (51-75), 63.9% male, 42.9% diabetic, 43.2% Caucasoid, 14.4% with a history of myocardial infarction, 8.4% coronary artery bypass surgery, dialysis vintage 28.2 (12.3-55.5) months. Median predialysis NT-proBNP 283 (123-989) pmol/l, and predialysis ECW/TBW ratio 0.397 ± 0.029. On multivariate analysis, predialysis log NT-proBNP was associated with predialysis systolic blood pressure (β 0.007, p = 0.000), weight (β −0.008, p = 0.001), valvular heart disease (β 0.342, p = 0.015, ECW/TBW (β 1.3, p = 0.019) and log CRP (β 0.145, p = 0.037). Dividing patients into NTproBNP quartiles, %ECW/TBW and relative ECW overhydration were significantly greater for the highest quartile vs. lowest (40.5 ± 4.1 vs. 39.0 ± 1.1, and 1.51 ± 1.24 vs. 0.61 ± 0.69 l, respectively, p < 0.001). Conclusion: In this study, predialysis NTproBNP values were associated with direct assessments of the extracellular volume excess measured by MFBIA and systolic arterial blood pressure. This suggests that predialysis NTproBNP values can potentially be used to aid clinical assessment of volume status in dialysis patients to determine target weight.

Extracellular hydration, cardiovascular risk, and the interstitium: a three-dimensional view

Volume expansion is a major contributor to poor cardiovascular outcomes in kidney disease. The relationship of extracellular volume (ECV) overload to cardiovascular changes in chronic kidney disease (CKD) remains speculative. Recent studies are challenging traditional concepts and providing new insight into mechanisms and the relationship of ECV to cardiovascular health. A dynamic role of the extracellular interstitium in inducing cardiovascular risk is emerging in CKD.