Gender,low Kt/V,and mortality in Japanese hemodialysis patients: Opportunities for improvement through modifiable practices

Guidelines have recommended single pool Kt/V > 1.2 as the minimum dose for chronic hemodialysis (HD) patients on thrice weekly HD. The Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that “low Kt/V” (<1.2) is more prevalent in Japan than many other countries, though survival is longer in Japan. We examined trends in low Kt/V, dialysis practices associated with low Kt/V, and associations between Kt/V and mortality overall and by gender in Japanese dialysis patients. We analyzed 5784 HD patients from Japan DOPPS (1999–2011), restricted to patients dialyzing for >1 year and receiving thrice weekly dialysis. Logistic regression models estimated the relationships of patient characteristics with Kt/V. Logistic models also were used to estimate the proportion of low Kt/V cases attributable to various treatment practices. Multivariable Cox regression was used to estimate the associations of low Kt/V, blood flow rate (BFR), and treatment time (TT), with all‐cause mortality. From 1999 to 2009, the prevalence of low Kt/V declined in men (37–27%) and women (15–10%). BFR <200 mL/min, TT <240 minutes, and dialyzate flow rate (DFR) < 500 mL/min were common (35, 13, and 19% of patients, respectively) and strongly associated with low Kt/V. Fifteen percent of low Kt/V cases were attributable to BFR <200 and 13% to TT <240, compared to only 3% for DFR <500. Lower Kt/V was associated with elevated mortality, more so among women (hazard ratio [HR] = 1.13 per 0.1 lower Kt/V, 95% CI: 1.07–1.20) than among men (HR = 1.06 per 0.1 lower Kt/V, 95% CI: 1.00–1.12). The relatively large proportion of low Kt/V cases in Japanese facilities may potentially be reduced 30% by increasing BFR to 200 mL/min and TT to 4 hours thrice weekly in HD patients. Associations of low Kt/V with elevated mortality suggest that modification of these practices may further improve survival for Japanese HD patients.     

Comparison of intradialytic blood pressure variability between conventional thrice‐weekly hemodialysis and short daily hemodialysis

Intradialytic blood pressure (BP) variability may be associated with increased mortality. We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice‐weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed‐effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP<90/55 mmHg at any time during HD). In addition to a predictor and outcomes, the demographics, estimated dry weight, and ultrafiltration ratio were examined. The median (range) age of the patients was 48 (34–77); all had hypertension, and 4 (33%) had diabetes. By a mixed effects linear regression model, the intradialytic systolic BP variability was 13.2 (quartile range 9.5–14.0) mmHg and 10.0 (8.3–10.9) mmHg for CHD and SDHD, respectively (P<0.006). Intradialytic diastolic BP variability was also significantly reduced (7.7 [6.4–9.2] vs. 6.1 [5.5–6.6] mmHg, P=0.005). Relative to CHD, less hypotension was observed during treatment on SDHD: the odds ratio (95% confidence interval) was 0.36 (0.16–0.81; P=0.008). In this retrospective study, SDHD was associated with less intradialytic BP variability and with fewer episodes of hypotension during treatments. Further studies are necessary to generalize these findings.     

The influence of blood volume-controlled ultrafiltration on hemodynamic stability and quality of life

Dialysis hypotension occurs frequently and is associated with increased morbidity, mortality, and may influence quality of life. We investigated the influence of blood volume (BV)-controlled ultrafiltration on hemodynamic stability and quality of life in a prospective multiple crossover study. Nineteen patients were consecutively treated with standard hemodialysis (HD), BV-controlled ultrafiltration, and again with standard ultrafiltration during 3-week phases, during which different hemodynamic parameters, ultrafiltrate quantities, dry weight, and quality of life were measured. Blood volume-controlled ultrafiltration resulted in increased hemodynamic stability: systolic blood pressure was significantly higher after treatment with BV-controlled HD compared with both standard treatments (p=0.018 and 0.043, respectively). Also, systolic blood pressure reduction, as a measure of blood pressure stability, was significantly smaller during the BV-controlled phase (-3.9 mmHg) compared with both standard phases (-13.7 and -11.0 mmHg): p=0.003 and 0.035, respectively. No difference was found in the occurrence of large decreases of blood pressure (>30 mmHg), decreases below 90 mmHg systolic pressure, or subjective complaints during treatment or after treatment between both treatment modalities. During the course of the study, the dry weight decreased significantly from mean 73.3 to mean 70.9 kg, and the amount of ultrafiltrate was significantly larger using BV-controlled HD compared with standard treatment (mean 2407 vs. mean 2266 mL; p=0.035). Quality of life, measured by visual analog scales (VAS), showed discrete but no consistent differences between study phases. We conclude that BV-controlled HD increases hemodynamic stability and ultrafiltrate amount compared with a standard treatment. No consistent change in quality of life is found between both treatment modalities.     

Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials

Hypertension is a common complication of chronic kidney disease and persists among most patients with end‐stage renal disease despite the provision of conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent HD on blood pressure in the randomized controlled Frequent Hemodialysis Network trials. The daily trial randomized 245 patients to 12 months of 6× (“frequent”) vs. 3× (“conventional”) weekly in‐center hemodialysis; the nocturnal trial randomized 87 patients to 12 months of 6× weekly nocturnal HD vs. 3× weekly predominantly home‐based hemodialysis. In the daily trial, compared with 3× weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by ?7.7 mmHg [95% confidence interval (CI): ?11.9 to ?3.5] and diastolic blood pressure by ?3.9 mmHg [95% CI: ?6.5 to ?1.3]. In the nocturnal trial, compared with 3× weekly HD, 2 months of frequent HD lowered systolic blood pressure by ?7.3 mmHg [95% CI: ?14.2 to ?0.3] and diastolic blood pressure by ?4.2 mmHg [95% CI: ?8.3 to ?0.1]. In both trials, blood pressure treatment effects were sustained until month 12. Frequent HD resulted in significantly fewer antihypertensive medications (daily: ?0.36 medications [95% CI: ?0.65 to ?0.08]; nocturnal: ?0.44 mediations [95% CI: ?0.89 to ?0.03]). In the daily trial, the relative risk per dialysis session for intradialytic hypotension was lower with 6×/week HD but given the higher number of sessions per week, there was a higher relative risk for intradialytic hypotensive requiring saline administration. In summary, frequent HD reduces blood pressure and the number of prescribed antihypertensive medications.     

Extracellular Volume Changes and Blood Pressure Levels in Hemodialysis Patients

Background: Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post‐HD body weight (BW) over a period of 3 to 4 months. Methods: During a period of 3–4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143–141 mmol/L to 139–138 mmol/L. Extracellular volume (ECV) was measured with a multiple‐frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical. Results: Group 1 showed a significant reduction during the entire 48‐hour period in systolic (156 ± 16 mmHg vs. 140 ± 14 mmHg, P = 0.030) and diastolic BP (97 ± 12 mmHg vs. 87 ± 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 ± 13 vs. 105 ± 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 ± 15 mmHg vs. 138 ± 14 mmHg, P = 0.007; diastolic BP 97 ± 12 mmHg vs. 85 ± 9 mmHg, P = 0.009) than during the day (157 ± 18 mmHg vs. 142 ± 15 mmHg, P = 0.067; diastolic BP 97 ± 13 mmHg vs. 90 ± 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48‐hour period (76 ± 24% vs. 46 ± 28%, P = 0.043) as well as in night systolic load (75 ± 21% vs. 41 ± 30%, P = 0.015) and night diastolic load (67 ± 32% vs. 39 ± 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2. Conclusions: The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.     

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.     

Characteristics of heart rate variability entropy and blood pressure during hemodialysis in patients with end-stage renal disease

Entropy (ENT) is a newly developed measure of the complexity of heart rate variability (HRV). The aim of this study was to characterize the complexity of HRV in patients with end-stage renal disease (ESRD) and to find a possible clinical utility. Healthy subjects and patients with ESRD undergoing hemodialysis (HD) were recruited. The HD population consisted of patients with and without diabetes mellitus (DM). An electrocardiogram was recorded before HD, and blood pressure was measured during HD. The coefficients of variation of R-R intervals, high- and low-frequency components, and ratio of the low- to high-frequency components were measured as variables of HRV. The ENT was used to describe the complexity of HRV. Forty-six healthy subjects and 27 HD patients participated in this study. The ENT negatively correlated with the duration of DM (p = 0.001), systolic blood pressure (p = 0.003), and mean blood pressure (p = 0.004) before a HD session. ENT in HD patients was lower than that in healthy subjects (p < 0.01). ENT in HD patients with DM was lower than that in HD patients without DM (p < 0.01). The change in systolic blood pressure (DeltaSBP) during a HD session showed high correlations to ENT and ultrafiltration rate (UFR) of the dialyzer. The following equation was obtained: DeltaSBP = 2.25 x ENT - 2.28 x UFR - 21.27 (R2 = 0.805; p < 0.0001). ENT decreased with uremic and diabetic status. ENT also represents a possible prediction of hypotension during a HD session.     

Residual renal function and arterial stiffness mediated the blood pressure change during interdialytic weight gain in hemodialysis patients

Volume overload is thought to be the main cause of hypertension in dialysis patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis (HD) patients, which was considered as an increase in extracellular water (ECW), on blood pressure (BP) change, was controversial. Our aim was to examine the changes in hemodynamics and arterial stiffness during IDWG in HD patients and attempt to explore the possible mechanism of diverse BP change. Thirty prevalent patients on HD were enrolled. The height, weight, BP, blood chemistry, volume status assessed by bioelectrical impedance analysis, hemodynamic parameters obtained by echocardiography, and pulse wave velocity (PWV) were collected within 1 hour postdialysis and again just before the next dialysis session. Meanwhile, blood samples were drawn to analyze vasoactive hormones, including renin, angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs during the next predialysis were significantly higher than those during the postdialysis. The BP showed no difference between postdialysis and the next predialysis. There was an obvious increase in cardiac output and decrease in total peripheral resistance as a whole during the next predialysis than that during postdialysis. When patients were divided into the BP increase group (BPI group, 13 patients) and BP decrease group (BPD group, 11 patients) according to the change in systolic BP higher than 10 mmHg, both groups displayed a significant increase in weight, ECW, cardiac output, and a decrease in total peripheral resistance. As compared with the BPI group, patients in the BPD group had significantly lower IDWG, shorter time on dialysis treatment, and higher residual renal function. A decrease in catecholamine and endothelin in the next predialysis was obvious in the BPD group. There was a significant decrease in PWV at the next predialysis in the BPD group while the PWV did not change significantly in the BPI group. Our results showed that the diverse BP change during IDWG was significantly affected by residual renal function, PWV, and vasoactive substances.     

Treatment of vitamin D deficiency/insufficiency with ergocalciferol is associated with reduced vascular access dysfunction in chronic hemodialysis patients

Vitamin D deficiency or insufficiency is highly prevalent among patients with chronic kidney disease (CKD). This study aims to determine the relationship between vitamin D and frequency of vascular access dysfunction (VAD) in hemodialysis (HD) patients. We reviewed medical records of all HD patients who had serum 25‐hydroxyvitamin D (25OHD) levels at 4 outpatient dialysis facilities between January 2011 and January 2012. Patients were included if they were ≥18 years of age, had been on maintenance dialysis for ≥3 months, and had native arteriovenous fistula or synthetic polytetrafluoroethylene grafts for dialysis access. Patients with catheters were excluded. 25‐Hydroxyvitamin D levels <30 ng/mL were documented in 183 patients (86%). Median and interquartile range [Q1, Q3] of 25OHD level was 16 [11, 25] ng/mL. Among 213 dialysis patients, 102 had VAD. Median 25OHD level was significantly lower in patients who had VAD than in those without VAD (14.5 [10, 22] vs. 19 [12, 27.5] ng/mL; P = 0.003). There was significant association between VAD and the lowest quartile relative to the highest quartile of 25OHD level. A 25OHD level <12 ng/mL was associated with more than doubling of risk for VAD (OR 2.56; 95% CI [1.05–6.23], P < 0.05). Of 213 patients, 140 were treated with ergocalciferol and 73 were not treated. Treatment was associated with significant reduction in VAD (OR = 0.36; 95% CI [0.19–0.68], P = 0.002). Vitamin D deficiency or insufficiency is an independent risk factor for VAD in HD patients; its treatment with ergocalciferol is associated with decreased VAD.     

Unphysiology Is the Major Factor Influencing Cardiovascular Instability during Hemodialysis

Background: Hemodialysis is often complicated by cardiovascular instability (CVI). We studied factors contributing to this problem during 720 hemodialyses (HDs) in 20 patients; 480 dialyses were 6/week and 240 were 3/week. Methods: Dependent variables were increase in pulse rate (PR) and maximal (MAX) and overall (OV) fall of systolic blood pressure (BP). Independent variables were dialyses/week (DIAL), ultrafiltration (Uf), % of body weight (BW), pre‐post BUN (ΔBUN), time on dialysis (T), speed of dialysis (K/V in mL min^–1 kg^–1 BW), target‐postdialysis BW (Ta‐Po BW), Kt/V, ΔPO4, Δbicarbonate, Δpotassium, ΔBUN, an ‘unphysiology index’ summing up changes in electrolytes, and BUN and BW during dialysis (UPI). The relations were analyzed by backward multiple regression analysis. Results: PR increased 0.5 ± 11/min; MAX BP fall was 23 ± 17 mmHg; OV BP fall was 12 ± 19 mmHg. In multiple stepwise backward regression analysis, independents in order of importance: PR = 38 – DIAL × 4 + T × 0.1 + Uf × 1.8 +ΔPO4 × 1.8 – UPI× 0.2 – K/V × 2, r = 0.30, p < 0.0001; MAX BP = UPI × 0.4 – ΔBUN × 0.3 + ΔPO4 × 2.6 + 11, r = 0.34, p < 0.0001; OV BP = UPI × 0.4 – ΔBUN × 0.3 +ΔPO4 × 2.7 + 1, r = 0.33, p < 0.0001. Conclusion: To prevent BP fall and tachycardia during hemodialysis, the most important factor to decrease is unphysiology, i.e., the oscillations in electrolytes, fluid spaces, and osmolality that occur during dialysis. The best way to do this is to dialyze patients daily. An unexpected finding worthy of further investigation was the large detrimental influence of ΔPO4 on CVI.     

Barriers to access before initiation of hemodialysis: a single-center review

Guidelines recommend that > or =50% of patients starting dialysis have a fistula. We reviewed our experience in consecutive incident patients over a 1-year period. Only 30 of the 93 patients starting hemodialysis had a fistula that was accessed. Late referral (nephrology contact <90 days) was a significant issue in 48% (30/63) of the patients without a fistula. Most (n=21) of the late referrals were acute disease; only 9 were late referrals of chronic disease. Nephrology follow-up exceeded 200 days in the remaining (33/63) without this access. In the cohort with sufficient nephrology referral, we explored variables associated with a fistula (n=30) compared with those without one (n=33). In multivariate logistic regression analysis, peripheral vascular disease (odds ratio [OR] 0.026, 95% confidence interval [CI] 0.002-0.286) and rapid loss of estimated glomerular filtration rate (eGFR) (OR 0.745 per mL/min/1.73 m(2)/year, 95% CI 0.625-0.888) in the year preceding dialysis were significant negative predictors for a fistula. Patients without access experienced faster declines in GFR in the year preceding dialysis (12.1+/-9.9 vs. 4.7+/-3.5 mL/min 1.73 m(2) with access, p<0.001). Glomerular filtration rate loss in the 2 years before starting dialysis was the same between the 2 groups (-0.54+/-10.4 vs. 1.42+/-3.9 mL/min 1.73 m(2)). Age, sex, diabetes, other comorbidity, length of nephrology follow-up, eGFR at dialysis start, hemoglobin, and albumin were not significant. At our center, rapid loss of renal function in otherwise stable chronic kidney disease (CKD) patients is more important than late referral of CKD for the lack of access. Improvements in rapid referral for access creation could help reduce this barrier.     

Patient‐specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one‐compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2‐hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K_M). In this report we determined K_M in patients treated by in‐center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8‐hour HD treatments where intradialytic and postdialytic plasma samples were collected; K_M values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K_M was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K_M values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K_M was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = ?0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one‐compartment model.     

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.     

Effect of ultrafiltration on placental‐fetal blood flow in pregnancy of woman undergoing chronic hemodialysis

Introduction: Patient who was undergoing hemodialysis (HD) thrice weekly usually gain 1 to 4 kg of weight in interdialytic period, mainly due to fluid accumulation by ingestion of water. Ultrafiltration (UF) during HD will be need to remove fluid excess to avoid severe medical complications secondary to fluid overload. However, in pregnant woman UF can increase the episodes of intradialytic hypotension which may lead to placental ischemic injury and predispose to fetal distress. There is little information about safe fluid amount withdrawn by UF during pregnancy. Methods: We prospectively study by obstetric Doppler ultrasonography the fluxometric parameters: pulsatility index (PI) and resistance index (RI) of fetal middle cerebral, uterine, and umbilical artery obtained at the beginning and the end of HD session, the acute and chronic effect of UF on placenta and fetus blood flow, as well as the fetal outcome in 1 pregnant woman on chronic HD. Findings: We did not observe any acute harmful effect on fetal middle cerebral, placental and umbilical artery blood flow when UF rate of 2.1 ± 0.04 L (6 < 8 mL/h/kg) during HD session, no significant statistical difference was observed when compared PI and RI before and after UF and also when we compared these data with reference value on normal pregnancy to the same gestational age. Discussion: UF rate of 6 < 8 mL/h/kg during HD did not bring any acute harmful effect on fetal middle cerebral, placental, and umbilical blood flow and the UF rate of 1.4 6 0.4 L (< 6 mL/h/kg) / HD session that was done in all others HD during pregnancy was safe, without any chronic fetal deleterious effect. Obstetric Doppler ultrasonography is a simple and noninvasive method to fetal follow‐up and can aid to determine safe UF rate in pregnant women during gestation.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

Role of T‐regulatory cells in the response to hepatitis B vaccine in hemodialysis patients

Human disease elicits a complex array of biological processes that results in long‐term protective immunological memory to infectious agents. Chronic kidney disease is known to impair induction of sustained immunological memory to hepatitis B vaccine (HBVax) antigens. We asked the question: Does end‐stage renal disease promote changes in subtypes of regulatory T (Treg) cells that correlate with diminished amnestic response to HBVax antigen compared to healthy controls? The study design and setting was a prospective observational cohort at a veterans affairs medical center. End‐stage renal disease patients on hemodialysis (HD) were compared with individuals with self‐reported normal kidney function. All subjects received HBVax. Peripheral blood was sampled for assessment for Treg cells pre and post vaccination. CD4+ FOXP3 Treg numbers were similar between HD and healthy subjects during a 14‐day time period post vaccination. HD subjcts had lower anti‐HBSag antibody than CON (control) subjects (330 ± 108.7 vs. 663.1 ± 129.7 IU/mL; P = 0.063). Hemodialysis subjects with resting Tregs higher than the median value in our cohort demonstrated a significantly lower change in HBsAB at 30 days post booster vaccination (P = 0.030). No such relationship was found for the activated Treg subset among HD subjects, or either subset among CON subsets. In our limited comparison study of 11 HD and 8 CON subjects, Treg subsets did not differ between the two groups; but differences in the suppressive Treg numbers in the HD group could explain the altered antibody response to HBVax and is worthy of further study.     

Determination of the critical absolute blood volume for intradialytic morbid events

The reduction of blood volume below a critical threshold is assumed to trigger intradialytic morbid events (IME). Recently, we presented a simple method to determine the absolute blood volume during routine hemodialysis (HD) carried out without blood sampling and without injection of dyes or radiolabeled markers. Such information could be used to detect excessive volume reduction during HD and to prevent IME. Therefore, we performed a pilot study in IME‐prone patients to identify the absolute blood volume at which they developed clinical symptoms. A volume of 240 mL of ultrapure dialysate was automatically infused into the extracorporeal circulation using the bolus function of a commercial online hemodiafiltration machine incorporating a blood volume monitor (BVM). The increase in relative blood volume (RBV) caused by the infusion was measured and used to determine the absolute blood volume at that time. The blood volume per kilogram body mass at the time of symptomatic IME was also determined. All IME‐prone patients of a single‐dialysis center were included in the study. Ten out of 12 patients became symptomatic at a specific blood volume between 65 and 56 mL/kg (mean 62 mL/kg) whereas RBV showed a wide scatter (82–97%). A specific blood volume of 65 mL/kg seems to represent the threshold for IME by this method. The technique could be completely automated without altering the hardware of the dialysis device. Present feedback systems for automated blood volume‐controlled ultrafiltration could be adapted to maintain absolute blood volume above this critical volume to safely prevent volume‐dependent IME.