Important role of blood rheology in atherosclerosis of patients with hemodialysis

Concerning a role of blood rheology for atherosclerosis in patients with hemodialysis (HD), little data are available. It may be due to the fact that the method for evaluating rheologic properties of circulating blood has been limited. We examined blood rheology in 118 HD patients by using microchannel array flow analyzer that makes it possible to directly observe the flow of blood cell elements through the microchannel. Transit time (T(B)) of heparinized whole blood through slit pores (7 x 30 microm) was used as an index of rheology and related with various inflammatory biomarkers such as high-sensitive CRP (hsCRP), monocyte chemotactic protein-1, osteopontin, or fibrinogen (Fg). Moreover, as a surrogate marker of atherosclerosis, carotid intima-media thickness (IMT) and aortic stiffness evaluated by brachial-ankle pulse-wave velocity (baPWV) were studied. In HD patients, T(B) had strong positive correlations with hsCRP (r = 0.427; p < 0.00001), Fg (r = 0.452; p < 0.00001), and osteopontin (r = 0.227; p < 0.0134). Further, T(B) was significantly well correlated with IMT (r = 0.400; p < 0.0001) and PWV (r = 0.470; p < 0.0001). Multivariate regression analysis showed that baPWV, IMT, Fg, hematocrit, white blood cell count, and CRP were chosen as significant explanatory factors for T(B.) These results suggest that blood rheology may play an important role for atherosclerosis in patients with HD.     

News and Traditional Indications from Short Daily Dialysis: Different Schemes to Optimized ESF Response

Dialysis adequacy indexed by Kt/V in hemodialysis (HD) patients is recommended as a single-pool Kt/V of at least 1.2 per session thrice weekly. But many patients cannot achieve this adequacy target. Although dialysis time is the most important as a factor influencing Kt/V, it is difficult to prolong dialysis time in practice because of its economic impact and poor patient compliance.
Objective:  The aim of this study is to investigate the effect of increasing blood flow rate on dialysis adequacy in HD patients with low Kt/V.
Methods:  This study enrolled 36 HD patients with single-pool Kt/V <1.2 per session thrice weekly, which was measured in dialyzer blood flow rate of 230 mL/min. We increased 15% of blood flow rate in patients <65 kg of body weight and 20% in patients >65 kg. And then we compared Kt/V and urea reduction ratio (URR) between before and after increasing blood flow rate.
Results:  The mean age was 48 ± 11 years (23–73 years), and the number of males was 25. Of the total patients, 24 patients had dry weight <65 kg. Mean dialysis duration was 52 ± 50 months (3–216 months). Mean Kt/V before increasing blood flow rate was 1.02 ± 0.09. It increased to 1.14 ± 0.12 after increasing blood flow rate (p < 0.001). Of the total 36 patients, 13 patients (36.1%) achieved adequacy target (Kt/V ≤ 1.2). Mean URR before increasing blood flow rate was 56.9 ± 4.0%. It also increased to 60.8 ± 4.1% (p < 0.001).
Conclusion:  Our data suggest that increasing blood flow rate by 15–20% of previous flow rate is effective in achieving dialysis adequacy in HD patients with low Kt/V.     

Does hemodiafiltration reduce vascular stiffness measured by aortic pulse wave velocity compared with high‐flux hemodialysis?

Hemodialfiltration (HDF) has been reported to reduce the frequency of intradialytic hypotension compared with hemodialysis (HD). We wished to determine whether HDF resulted in improvement of arterial stiffness compared with HD. We reviewed peripheral blood pressure and pulse wave velocity measurements in a cross‐sectional analysis of stable HDF and HD outpatients. One hundred forty‐one HDF patients were matched to 148 HD patients in terms of age, sex, prevalence of diabetes, peripheral blood pressure, and body mass. Pulse wave velocity was not different between the HD and HDF cohorts (median 9.1 [8.0–10.7] m/s vs. 9.7 [8.5–11.6] m/s). Similarly, there were no differences in central aortic pressure (149.2 ± 30.9 mmHg vs. 151.9 ± 35.2 mmHg), or aortic (39 [25.1–51.2]% vs. 38.6 [25.8–51.4]%) and brachial (3.8 [?24.3 to 26.9]% vs. 3 [?22.4 to 27.1]%) augmentation indices, respectively. Pulse wave velocity did not differ between adult patients treated by HD and HDF, and similarly, there were no differences in central aortic pressure, aortic or brachial augmentation indices, and cardiac diastolic perfusion. Our study suggests that HDF does not appear to offer any benefit over HD in terms of vascular stiffness.     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

Accuracy of Doppler Ultrasonography in Measuring Radial Artery Wall Thickness in Hemodialysis Patients: Comparison with Histologic Examination

Increased radial artery wall thickness (RAWT) is considered to be associated with early failure of radiocephalic arteriovenous fistula (AVF) as well as coronary artery atherosclerosis in hemodialysis patients. Therefore, exact measurement of RAWT by noninvasive method before the operation is very important.
Objective:  This study was designed to evaluate accuracy of Doppler ultrasonography in measuring RAWT in hemodialysis patients.
Methods:  This study enrolled 21 hemodialysis patients undergoing radiocephalic AVF operation for the first time. We measured RAWT (intima-media thickness) using high-resolution Doppler ultrasonography at the wrist before the AVF operation. We obtained specimens of the radial artery during the AVF operation and then measured RAWT by histologic examination.
Results:  Mean age of the patients was 60 ± 13 years and the number of females was 7 (33.3%). Mean values of RAWT measured by Doppler ultrasonography and histologic examination were 485 ± 93 μm (300–700 μm) and 426 ± 106 μm (300–700 μm), respectively. The value of RAWT of Doppler sonographic measurement well correlated with that of histologic measurement (r = 0.800, p < 0.001).
Conclusion:  Our data suggest that Doppler ultrasonography is an effective tool in measuring RAWT in hemodialysis patients before AVF operation.     

Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.     

Treating mineral metabolism disorders in patients undergoing long hemodialysis: A search for an optimal strategy

In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 ± 0.1 to 1.5 ± 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca × P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non–calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.     

Bioreactance: A new tool for cardiac output and thoracic fluid content monitoring during hemodialysis

Outpatient hemodialysis therapy (HD) can be associated with hemodynamic compromise. Bioreactance^® has recently been shown to provide accurate, noninvasive, continuous, measurements of cardiac output (CO) and thoracic impedance (Zo) from which thoracic fluid content (TFC) can be derived assuming TFC=1000/Zo. This study was designed to evaluate the changes in TFC in comparison with the traditional indices of fluid removal (FR) and to understand the trends in CO changes in HD patients. Minute-by-minute changes in TFC and CO were prospectively collected using the bioreactance system (NICOM^®) in HD patients of a single unit. Changes in body weight (ΔW), hematocrit (ΔHct), and amount of FR were also measured. Twenty-five patients (age 77 ± 11 years) were included. The TFC decreased in all patients by an average of 5.4 ± 7.9 kΩ⁻¹, weight decreased by 1.48 ± 0.98 kg, and FR averaged 2.07 ± 1.93 L over a 3- to 4-hour HD session. There were good correlations between ΔTFC and ΔW (R=0.80, P<0.0001) and FR (R=0.85, P<0.0001). ΔHct (4.13 ± 3.42%) was poorly correlated with ΔTFC (R=0.35, P=0.12) and FR (R=0.40, P=0.07). The regression line between FR and TFC yielded FR=1.0024−0.1985TFC; thus, a 1 kΩ⁻¹ change of Zo correlates with an ∼200 mL change in total body water. The change in CO (−0.52 ± 0.49 L/min m²) during HD did not correlate with FR (R=0.15, P=NS). Changes in TFC represented the monitored variable most closely related to FR. CO remained fairly constant in this stable patient cohort. Further studies in high-risk patients are warranted to understand whether TFC and CO monitoring can improve HD session management.     

Higher arteriovenous fistulae blood flows are associated with a lower level of dialysis-induced cardiac injury

Native arteriovenous fistulae (AVF) remain the vascular access of choice for hemodialysis (HD). Despite being associated with superior long-term outcomes (cf. catheter use), little is known about the systemic hemodynamic consequences of AVFs. Repetitive myocardial injury (myocardial stunning) is an under-recognized common consequence of HD. The aim of this study was to examine the impact of AVF flow (Qa) on dialysis-induced cardiac injury. We studied 50 chronic HD patients. All patients underwent echocardiography (and subsequent quantitative offline analysis) at baseline, during and post dialysis, to assess left ventricular function and the development of regional wall motion abnormalities. Qa was measured using ionic dialysance. Patients were divided into Qa tertiles (<500, mean 291±101 mL/min, 500–1000, mean 739±130 mL/min and >1000, mean 1265±221 mL/min). There were no significant differences between the groups in terms of age, sex, diabetes, or resting ejection fraction. Patients with Qa>1000 mL/min had a lower prevalence of left ventricular hypertrophy (55% vs. 76%, P=0.01). Dialysis-induced myocardial stunning (seen in 65% of the patients studied) was significantly and sequentially reduced in those patients with higher Qas. This was seen in a lower number of segments and ventricular regions developing regional wall motion abnormalities, as well as a significantly reduced mean and cumulative percentage reduction in fractional shortening of those ventricular segments affected (−187±37%, −161±26%, and −101±25%, respectively, P=0.04). Relatively higher AVF flows appear to be associated with a lower level of observed HD-induced cardiac injury.     

Low cholesterol along with inflammation predicts morbidity and mortality in hemodialysis patients

Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients' characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 ± 21.49 vs. 5.51 ± 4.57 pg/mL (P<0.018) and TChol 167.37 ± 47.84 vs.122.04 ± 26.48 mg/dL (P<0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 ± 11.54 vs. 23.15 ± 18.76 mg/L (P<0.000) and TChol 169.26 ± 46.42 vs. 133.26 ± 46.33 mg/dL (P<0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130)—an antagonist of IL-6 action—were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients.     

Mini mental status examination (MMSE) in stable chronic renal failure patients on hemodialysis: The effects of hemodialysis on the MMSE score. A prospective study

Cognitive impairment is common in hemodialysis (HD) patients. The mini mental status examination is a simple screening test for dementia. The objectives of this study were to (1) study and compare the predialysis and postdialysis mini mental status examination score and 2 subscores and compare them with those of a control group and (2) determine the factors affecting these scores. This was a prospective study of 54 HD patients, which involved calculation of their predialysis (PrHDSc) and (2–4 weeks later) postdialysis (PoHDSc) scores and comparison of these with the control scores (CoSc). The mean scores for PreHDSc and PoHDSc were 26.5±2.7 and 26.4±3.3, respectively. Both were significantly lower than CoSc, 28.4±1.6 (95% CI for score difference 0.99–2.97, P<0.001). The subscores for orientation, registration, and recall (ORR) and attention (ATT) before and after HD were 14.2±1.3, 14.3±1.8, and 3.5±1.7, 3.2±1.8, respectively. Both were significantly lower than the CoSc, 15.2±1.2 and 4.2±1.1 (P=0.001 and 0.004, respectively). There were no significant differences between the PrHDSc and PoHDSc (P values of 0.87, 0.63, and 0.45, respectively). Patients' PrHDSc correlated positively with PoHDSc and dialysis efficiency measured by the urea reduction ratio and Kt/V (r=0.58, 0.4, and 0.34, respectively). Education level correlated positively with PrHDSc r=0.41 but not PoHDSc. Hemodialysis duration correlated negatively with PrHDSc r=−0.3. There was no correlation among age, chronic renal failure duration, HD frequency, weight loss, systolic or diastolic blood pressure drop, and PrHDSc or PoHDSc. Hemodialysis patients scored significantly less than the control patients. Their score was not affected by HD. This may reflect the stable cognitive function/dysfunction or the mild sensitivity of the test.     

Effect of sevelamer on aortic pulse wave velocity in patients on hemodialysis: a prospective observational study

Aortic stiffening and aortic calcification are risk factors for cardiovascular events in hemodialysis (HD) patients, and these 2 risk factors are interrelated. Sevelamer decreases aortic calcification but its effect on aortic stiffness has not been investigated previously. Thirteen HD patients commencing sevelamer treatment and 13 matched controls were followed for 11 months. Aortic pulse wave velocity (PWV), augmentation index (AIx), and levels of inhibitors of vascular calcification (fetuin-A, matrix-GLA-protein, osteoprotegerin/RANKL) were measured at baseline and at the end of follow-up, and the differences between the groups were compared. Determinants of the changes in PWV during follow-up were assessed by multivariate linear regression. At baseline, PWV was 9.93 (2.10) m/s in sevelamer-treated patients and 9.20 (2.84) m/s in control patients (p=0.464). By the end of follow-up, PWV decreased by 0.83 (2.3) m/s in sevelamer-treated patients while it increased by 0.93 (1.88) m/s in controls (p=0.042). The direction of changes in AIx were similar, but not statistically significant. There were no significant differences in the levels of inhibitors of calcification either at baseline or during follow-up. In multivariate linear regression sevelamer treatment, diabetes, heart rate, and C-reactive protein were related to the change in PWV. These data suggest that sevelamer treatment is associated with an improvement in aortic stiffness in HD patients, but it does not seem to affect serum levels of inhibitors of vascular calcification.     

Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients

Vascular calcification is associated with a poor prognosis in dialysis patients. It can be assessed with computed tomography but simple inoffice techniques may provide useful information. We compared the results obtained with a simple noninvasive technique with those obtained using multidetector computed tomography for aortic arch calcification volume (AoACV) in chronic hemodialysis (HD) patients. The enrolled study subjects were 63 (32 men and 31 women) maintenance HD patients. Calcification of the aortic arch was semiquantitatively estimated with a AoAC score (AoACS) on plain chest radiology. The AoACV was increased, with a mean value of 6.6 ranging from 0% to 36.5%. The coefficient of intraobserver variation was less than 2.5%. Aortic arch calcification score was highly correlated with AoACV (r=0.635, P<0.001). Multiple regression analysis showed age (F value=12.62, P<0.001) and pulse pressure (F value=4.54, P=0.037) to be significant independent determinants of AoACS. In conclusion, a simple measurement of AoACS may be useful for inoffice imaging to choose a therapeutic regimen in HD patients.     

Changes of Plasma Amino Acid Profile in Hemodialysis Patients

Background:  The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP, and interleukin-6 (IL-6) in HD patients.
Methods:  The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who were treated by on standard HD for at least 6 months. The patients were divided in two groups, depending on the presence (HCV+) or absence (HCV–) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured, and the values were compared with 22 healthy controls.
Results:  The median of hsCRP, IL-6, and the hsCRP/IL-6 ratio were: 3.5 vs. 2.1 mg/L, p < 0.05; 4.3 vs. 0.9 pg/mL, p < 0.0001; and 0.8 vs. 2.7 pg/mL, p < 0.0001 for patients and controls, respectively. Age, gender, S-Alb, IL-6, and hsCRP did not differ between the HCV+ and HCV– patients. However, HCV+ patients had higher ALT (29 ± 21 vs. 21 ± 25 UI/L) and had been a longer time on HD (6.1 ± 3.0 vs. 4.0 ± 2.0 years) (p < 0.0001), respectively. Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs. 0.9; p < 0.05) as compared to the HCV group.
Conclusion:  The finding that the hsCRP/IL-6 ratio was lower in HCV+ patients than in HCV– patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP may be required to define inflammation in HD patients.     

Factors associated with serum magnesium and vascular stiffness in maintenance hemodialysis patients

Introduction : We evaluated the associated factors of serum magnesium in patients on maintenance hemodialysis (MHD). Furthermore, we evaluated the relationship between low serum magnesium and arteriosclerosis in these patients. Methods : In 129 patients on MHD, we evaluated the blood levels of magnesium, brachial‐ankle pulse wave velocity (ba‐PWV), ankle‐brachial index (ABI), and intima‐media thickness of the common carotid artery (IMT). Findings : In MHD patients, the serum level of magnesium was significantly correlated with age, calcium, TNF‐α, albumin, and ba‐PWV but not with ABI or IMT. In the multiple regression analysis, albumin (P = 0.0001, β = 0.31) and calcium (P = 0.029, β = 0.18) were selected as significant predictors of the magnesium level in MHD patients. Furthermore, the serum level of magnesium, as well as systolic blood pressure (P = 0.0001, β = 0.32) and age (P = 0.005, β = 0.25), were selected as significant (P = 0.012, β = ?0.22) predictors of ba‐PWV in MHD patients. Discussion : In MHD patients, the serum magnesium level was associated with the serum levels of calcium and albumin. Furthermore, a low serum magnesium level in MHD patients was associated with the index of vascular stiffness.     

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients

Introduction: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT‐1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT‐1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT‐1 levels might be a novel biomarker in early atherosclerosis. Methods: Forty‐five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high‐resolution B‐mode ultrasonography. Biomarker levels were measured in serum of patients. Findings: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT‐1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT‐1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT‐1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. Discussion: In conclusion, this is the first report showing that serum CHIT‐1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.     

Categorization of the hemodynamic response to hemodialysis: The importance of baroreflex sensitivity

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. The baroreflex arc is under autonomic control and regulates blood pressure. This study aimed to investigate the contribution of impaired baroreflex sensitivity (BRS) to the pathophysiology of IDH. Thirty-four chronic HD (12 IDH-prone, 22 IDH-resistant) patients underwent BRS measurement during HD with relative blood volume monitoring. During analysis, patients were separated into four age-matched groups according to resting BRS≥4.5 ms/mmHg and hemodynamic stability. Resting BRS was extremely heterogenous (geometric mean BRS 5.78±1.41 [range 1.76–41.41] ms/mmHg). Relative blood volume reduction was well matched in all groups (mean reduction in relative blood volume for all patients −6.74%±0.86%, P>0.05). Thirty-seven episodes of IDH occurred in the IDH prone, reduced BRS group. Patients with impaired resting BRS and prone to IDH had markedly different responses to HD as compared to the preserved BRS group, but the total peripheral resistance response was significantly lower than in the IDH-resistant patients (15.9%±2.1% vs. 42.4%±3.0%, respectively, P<0.001). In those patients prone to IDH and with impaired resting BRS, percentage reduction in cardiac output at the end of HD highly correlated with reduction in relative blood volume (r=0.94, P=0.006). Hypotension during dialysis may be an important source of recurrent cardiac injury and early recognition of those patients prone to relative symptomatic and asymptomatic hypotension remains important. Impaired resting BRS and recognition of a suboptimal peripheral pressor response, appear to predict those patients most likely to undergo hemodynamic instability and may assist in the pursuit of this elusive goal.     

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy‐one chronic HD patients and 65 age‐ and sex‐matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high‐performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.     

Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension

Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow-mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid-femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow-mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow-mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross-sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology.