Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study

Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case‐control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C‐reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis.     

Hypoalbuminemia is an important risk factor of hypotension during hemodialysis

Hypotension during hemodialysis (HD) is an important problem in patients on HD. To investigate the risk factors that contribute to the hypotension during HD, we compared background factors of hypotensive (HP) patients during HD. Among 58 patients undergoing HD in Tamura Memorial Hospital, 12 patients could not continue full HD because of hypotension. We compared the data of ultrafiltration volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP patients (HP group; n=12) and sex- and age-matched control patients (NP group; n=12). There were no significant differences of age, sex, and duration of HD between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%, p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP 3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2 groups. There is a significant negative correlation between changes of systolic blood pressure (delta systolic blood pressure) and serum albumin in these patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia is a major risk factor of hypotension during HD.     

Reducing the risk of intradialytic hypotension by altering the composition of the dialysate

Hypotension is the most common complication of outpatient hemodialysis sessions, with a reported prevalence of 4% to 31%, depending on which definition has been used and whether patients are symptomatic and nursing interventions were required. Dialysis centers which mix the dialysate in the dialysis machine have the opportunity to individualize the composition of the dialysate for patients. This permits a choice of dialysate sodium, potassium, calcium, magnesium, bicarbonate, acetate, and citrate concentrations and temperature. Studies have reported a higher intradialytic systolic blood pressure and fewer episodes of intradialytic hypotension when using a higher dialysate sodium, calcium, magnesium concentrations and lower temperature, but no clinical advantage for changing the potassium, bicarbonate, or citrate for acetate concentrations. The introduction of newer technology allowing real time measurements of plasma electrolyte concentrations will potentially allow changing the dialysate composition to reduce the risk of intradialytic hypotension without increasing the risk of positive electrolyte balances.     

Adrenal insufficiency presenting as unexplained hypotension in nocturnal home hemodialysis

Adrenal insufficiency is a complication of chronic corticosteroid therapy. Unexplained hypotension may be a manifestation of an adrenal insufficient state in patients with a history of corticosteroid therapy on hemodialysis. We present a series of five cases of patients on nocturnal home hemodialysis with hypotension as the main manifestation of adrenal insufficiency. Unexplained hypotension in patients with a history of corticosteroid therapy should prompt the managing clinician to consider adrenal insufficiency as a possible cause.     

Intradialytic changes of serum magnesium and their relation to hypotensive episodes in hemodialysis patients on different dialysates

Magnesium is a crucial mineral, involved in many important physiological processes. Magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients. Intradialytic hypotension is a common complication of dialysis and it is more common with acetate dialysate. The significance of the intradialytic changes of magnesium and their relation to parathyroid hormone (PTH) level and calcium changes during dialysis, and their relation to hypotensive episodes during dialysis are interesting. The aim of this work is to investigate the intradialytic changes of serum magnesium in chronic hemodialysis patients with different hemodialysis modalities and the relation to other electrolytes and to PTH, and also the relation to intradialytic hypotension. The present study was conducted on 20 chronic renal failure patients. All patients were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate-based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH during a hemodialysis session, the same patients were shifted to bicarbonate dialysis (group II). All patients were subjected to full history and clinical examination, predialysis laboratory assessment of blood urea nitrogen (BUN), serum creatinine, albumin, and hemoglobin, serial assessment of magnesium, calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis session, 2 hr later, and at the end of the session, blood pH, and electrocardiogram (ECG) presession and postsession. All patients were urged to fix their dry weight, diet, and current medications. None of the patients had diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on magnesium-containing drugs or previously parathyroidectomized. Hemodialysis sessions were performed by volumetric dialysis machines using the same electrolyte composition. Magnesium level significantly increased in the bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1, and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33 mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate group (p=0.024) but not in the acetate group. Phosphorus level significantly decreased in both acetate and bicarbonate groups. PTH level did not significantly change in either group, p value > or =0.05. Blood pH significantly increased, changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG showed no significant changes during sessions with either type of dialysate. Hypotension was significantly higher in group I compared with group II (p=0.01), and this hypotension was positively correlated with a decrease in serum magnesium level in group I. Intradialytic changes in serum magnesium have no correlation with intradialytic changes in serum calcium or with PTH level. However, it was significantly correlated with hypotension during the dialysis session, especially with acetate dialysate. Further investigations are needed to determine whether or not this is true in patients using bicarbonate dialysis.     

The relationship between symptoms and blood pressure during maintenance hemodialysis

Intradialytic hypotension (IDH) is a detrimental complication of maintenance hemodialysis, but how it is defined and reported varies widely in the literature. European Best Practice Guideline and Kidney Disease Outcomes Quality Initiative guidelines require symptoms and a mitigating intervention to fulfill the diagnosis, but morbidity and mortality outcomes are largely based on blood pressure alone. Furthermore, little is known about the incidence of asymptomatic hypotension, which may be an important cause of hypoperfusion injury and impaired outcome. Seventy‐seven patients were studied over 456 dialysis sessions. Blood pressure was measured at 15‐minute intervals throughout the session and compared with post‐dialysis symptom questionnaire results using mixed modeling to adjust for repeated measures in the same patient. The frequency of asymptomatic hypotension was estimated by logistic regression using a variety of commonly cited blood pressure metrics that describe IDH. In 113 sessions (25%) where symptoms were recorded on the questionnaire, these appear not to have been reported to dialysis staff. When symptoms were reported (293 sessions [64%]), an intervention invariably followed. Dizziness and cramp were strongly associated with changes in systolic blood pressure (SBP), but not diastolic blood pressure. Nausea occurred more frequently in younger patients but was not associated with falls in blood pressure. Thresholds that maximized the probability of an intervention rather than a session remaining asymptomatic were SBP <100 mmHg or a 20% reduction in SBP from baseline. The probability of SBP falling to <100 mmHg in an asymptomatic session was 0.23. Symptoms are frequently not reported by patients who are hypotensive during hemodialysis, which leads to an underestimation of IDH if symptom‐based definitions are used. A revised definition of IDH excluding patient‐reported symptoms would be in line with literature reporting morbidity and mortality outcomes and include sessions in which potentially detrimental asymptomatic hypotension occurs.     

Myocardial contractile function and intradialytic hypotension

Dialysis‐induced hypotension remains a significant problem in hemodialysis (HD) patients. Numerous factors result in dysregulation of blood pressure control and impaired myocardial reserve in response to HD‐induced cardiovascular stress. Episodic intradialytic hypotension may be involved in the pathogenesis of evolving myocardial injury. We performed an initial pilot investigation of cardiovascular functional response to pharmacological cardiovascular stress in hypotension‐resistant (HR) and hypotension‐prone (HP) HD patients. We studied 10 matched chronic HD patients (5 HP, 5 HR). Dobutamine‐atropine stress (DAS) was performed on a nondialysis short interval day, with noninvasive pulse‐wave analysis using the Finometer^® to continuously measure hemodynamic variables. Baroreflex sensitivity was assessed at rest and during DAS. Baseline hemodynamic variables were not significantly different. The groups had differing hemodynamic responses to DAS. The Mean arterial pressure was unchanged in the HR group but decreased in HP patients (?13.6 ± 3.5 mmHg; P<0.001). This was associated with failure to significantly increase cardiac output in the HP group (cf. increase in cardiac output in the HR group of +33.4 ± 6%; P<0.05), and a reduced response in total peripheral resistance (HP ?10.3 ± 6.8%, HR ?22.7 ± 2.9%, P=NS). Baroreflex sensitivity was not significantly different between groups at baseline or within groups with increasing levels of DAS; however, the mean baroreflex sensitivity was higher in HR cf. HP subjects throughout pharmacological stress (P<0.05). Hypotension‐prone patients appear to have an impaired cardiovascular response to DAS. The most significant abnormality is an impaired myocardial contractile reserve. Early identification of these patients would allow utilization of therapeutic strategies to improve intradialytic tolerability, potentially abrogating aggravation of myocardial injury.     

Interactions between intradialytic central venous oxygen saturation,relative blood volume,and all-cause mortality in maintenance hemodialysis patients

Introduction

In maintenance hemodialysis (HD) patients, low central venous oxygen saturation (ScvO₂) and small decline in relative blood volume (RBV) have been associated with adverse outcomes. Here we explore the joint association between ScvO₂ and RBV change in relation to all-cause mortality.

Methods

We conducted a retrospective study in maintenance HD patients with central venous catheters as vascular access. During a 6-month baseline period, Crit-Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO₂ and hematocrit-based RBV. We defined four groups per median change of RBV and median ScvO₂. Patients with ScvO₂ above median and RBV change below median were defined as reference. Follow-up period was 3 years. We constructed Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO₂ and RBV and all-cause mortality during follow-up.

Findings

Baseline comprised 5231 dialysis sessions in 216 patients. The median RBV change was −5.5% and median ScvO₂ was 58.8%. During follow-up, 44 patients (20.4%) died. In the adjusted model, all-cause mortality was highest in patients with ScvO₂ below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37–29.06), followed by patients with ScvO₂ below median and RBV change below median (HR 5.04; 95% CI 1.14–22.35), and ScvO₂ above median and RBV change above median (HR 4.52; 95% CI 0.95–21.36).

Discussion

Concurrent combined monitoring of intradialytic ScvO₂ and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO₂ and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload.     

Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: A pilot study

Observational data suggest that elevated magnesium levels in dialysis patients may prevent vascular calcification and in vitro magnesium can prevent hydroxyapatite crystal growth. However, the effects of magnesium on vascular calcification and bone mineral density have not been studied prospectively. Seven chronic hemodialysis patients participated in this open label, prospective pilot study to evaluate the effects of a magnesium-based phosphate binder on coronary artery calcification (CAC) scores and vertebral bone mineral density (V-BMD) in patients with baseline CAC scores >30. Magnesium carbonate/calcium carbonate (elemental Mg: 86 mg/elemental Ca 100 mg) was administered as the principal phosphate binder for a period of 18 months and changes in CAC and V-BMD were measured at baseline, 6, 12, and 18 months. Serum magnesium levels averaged 2.2±0.4 mEq/L (range: 1.3–3.9 mEq/L). Phosphorus levels (4.5±0.6 mg/dL) were well controlled throughout the 18 months study. Electron beam computed tomography results demonstrated a small not statically significant increase in absolute CAC scores, no significant change in median percent change, and a small none significant change in V-BMD. Magnesium may have a favorable effect on CAC. The long-term effect on bone mineral density remains unclear. Larger studies are needed to confirm these findings.     

Pulse contour-derived cardiac output in hemodialysis patients

Reliable methods for cardiac output determination are essential for studying the pathophysiology of intradialytic hypotension. Use of the current gold standard, the Transonic^® monitor, requires an arteriovenous fistula. We wished to verify the accuracy of a method based on finger pulse contour analysis, namely the Finometer^® monitor (FNM) for further use on patients dialyzing on a central vascular catheter. Fifty simultaneous cardiac output measurements were obtained during hemodialysis sessions in 25 patients. The internal variability of the FNM measurements was assessed by comparing 24 pairs of immediately successive measurements. The variability of successive FNM measurements was small (bias 0.28%, SD ± 6.1%; NS). The absolute cardiac output values reported by the FNM were unreliable (bias 20.1%, SD ± 35.3%; P<0.001) as were the relative intradialytic changes (r²=0.01). Excluding participants from the analysis due to old age, high dialysis vintage or a suspicion of atherosclerosis did not improve the results. Our findings do not support the use of pulse contour analysis for measuring cardiac output in hemodialysis patients. Uremic vascular disease may be the cause of the observed inaccuracy.     

Effect of mineralocorticoids on interdialytic weight gain in hemodialysis patients with perdialytic hypotension

Fludrocortisone is recommended in patients with orthostatic hypotension and a benefit has been suggested in hemodialysis patients with severe hypokaliemia. We report 2 patients who suffered from chronic severe perdialytic hypotension resistant to midodrine and who were treated in a long-term period with fludrocortisone. A rise of post-dialytic BP was observed with a decrease of the interdialytic weight gain (IWG). We suggest that the IWG decrease is induced by a lessening of the renin angiotensin aldosterone system that could be less stimulated at the end of the dialysis session because of a better-preserved arterial pressure. The decrease of angiotensin could lessen the feeling of thirst.     

Associations among nocturnal sleep,daytime intradialytic sleep,and mortality risk in patients on daytime conventional hemodialysis: US Renal Data System special study data

Fragmented nocturnal sleep is commonly reported by patients undergoing daytime conventional hemodialysis (CHD) and may be associated with higher mortality risk. Subjective sleepiness during CHD is also frequently observed. We examined the association of reported sleep fragmentation and nocturnal and daytime (intradialytic) sleep durations with survival in a national cohort of 1440 CHD patients who were interviewed in 2005–2007 in a phone survey conducted by the US Renal Data System. Patient survival was followed through September 30, 2010 in the US Renal Data System. A total of 76% of patients reported that they typically dozed off or slept during their treatment, and intradialytic dozing was especially common among patients whose treatment shift started before 1000 hours. There was a trend for patients who reported dozing during CHD to report nocturnal sleep fragmentation (60.4% vs. 55.1%; P = 0.07). With adjustment for intradialytic sleep and other covariates, nocturnal sleep fragmentation was not associated with survival. Mortality risk was higher for patients who reported sleeping 9 or more hours/night compared with the referent category of nocturnal sleep equal to 6–7 hours (hazard ratio: 1.50 [95% confidence interval: 1.04–2.17]; P = 0.03). Continued investigation of the association of timing and duration of sleep with hemodialysis patient outcomes is warranted.     

A meta‐analysis of sodium profiling techniques and the impact on intradialytic hypotension

Introduction Hemodialysis has improved in recent years, however, despite such improvements, intra‐dialytic hypotensive episodes still persist which can lead to a reduction in the overall effectiveness of the treatment. Profiling sodium levels during dialysis can improve vascular refilling and therefore may prevent hypotensive events. A number of profiling methods exist and this meta‐analysis set out to examine the effectiveness of these methods. Methods To assess the effectiveness of hemodialysis sodium profiling techniques. A review and meta‐analysis analytical framework was used. A search was conducted using Medline, Embase and CINAHL, Scopus and Web of Knowledge between 1946 and 2014 of published English‐language peer reviewed randomized control studies. In total 10 articles were retrieved and included in the review. All data was abstracted with a standardized data collection form. Stata 11.2 (Stata Corp) was used to analyse the data. Actual numbers of hypotensive events were pooled between studies. Analysis of subgroups was performed on sodium profile type. The data were further investigated using meta‐regression. Publication bias was also tested. Findings Stepwise profiling was shown to be statistically significantly effective in reducing intradialytic episodes. Results demonstrated that linear sodium profiling was not effective in reducing hypotensive events during dialysis. Discussion This review has shown that using stepwise profiling is more effective at reducing intra‐dialytic symptoms than other profiling methods. There was no evidence that linear profiling method was any more effective than conventional dialysis and in fact the results showed the reverse.