A simple method to estimate phosphorus mobilization in hemodialysis using only predialytic and postdialytic blood samples

We have recently developed a pseudo one-compartment model to describe intradialytic and postdialytic rebound kinetics of plasma phosphorus. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter; the phosphorus mobilization clearance (K(M) ). In this work, we propose a simple method to estimate K(M) from predialytic and postdialytic plasma phosphorus concentrations. Clinical data were collected from 22 chronic hemodialysis patients that underwent a 4-hour treatment session. A simple algebraic equation was derived from the pseudo one-compartment model to determine K(M) from predialytic and postdialytic plasma phosphorus concentrations. K(M) values computed using this equation were compared with values obtained from nonlinear regression of the full kinetic model to frequent intradialytic and postdialytic measurements of plasma phosphorus concentrations. There was good agreement between K(M) values (concordance correlation coefficient of 0.94) obtained from the simple method (105?±?52?mL/min, mean?±?SD) and from the full model (99?±?47?mL/min). The 95% confidence interval for the difference between estimated K(M) values was -26 to 36?mL/min. The proposed simple method requires the use of only predialytic and postdialytic blood samples to estimate patient specific K(M) ; this approach may allow easy clinical evaluation of phosphorus kinetics in hemodialysis patients.     

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost‐efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross‐over design: high‐flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.     

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.     

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.     

Risk factors associated with elevated serum pancreatic amylase levels during hemodialysis

Elevated levels of serum pancreatic enzymes are frequently observed in hemodialysis (HD) patients. The complex hemodynamic, biochemical, and physiological alterations in uremia were speculated to cause excessive release of pancreatic enzymes beyond decreased renal clearance. However, hemodynamic factors are seldom explored in this aspect. We performed the study to evaluate the association between intradialytic hemodynamic change and elevated serum pancreatic amylase (SPA). Eighty‐three prevalent HD patients without any clinical evidence of acute pancreatitis underwent pre‐HD and post‐HD blood sampling for serum pancreatic enzyme levels. Demographic, biochemical, and hematological data were collected from patient record review. Hemodialysis information including intradialytic blood pressure changes and ultrafiltration (UF) amount were collected and averaged for 1 month before the blood sampling day. Patients with elevated SPA during the HD session had greater mean systolic blood pressure and mean arterial pressure reduction, greater UF volume, greater pre‐HD blood urea nitrogen and serum creatinine, higher serum phosphorus, lower pre‐HD serum total CO₂, and lower left ventricle ejection fraction (LVEF). Using multivariate linear and logistic regression analysis, the independent predictors of elevated SPA were determined to be mean arterial pressure reduction during HD, mean UF amount, pre‐HD serum total CO₂, and LVEF. Greater blood pressure reduction during HD, greater UF volume, lower pre‐HD serum total CO₂, and lower LVEF were significantly associated with elevated SPA during HD. This suggests that hemodynamic factors contribute to elevated serum pancreatic enzymes in HD patients.     

Modifications to bicarbonate conductivity: A way to increase phosphate removal during hemodialysis? Proof of concept

Introduction Hyperphosphatemia and cardiovascular mortality are associated particularly with end‐stage renal disease. Available therapeutic strategies (i.e., diet restriction, calcium [or not]‐based phosphate binders, calcimimetics) are associated with extrarenal blood purification. Compartmentalization of phosphate limits its depuration during hemodialysis. Several studies suggest that plasmatic pH is involved in the mobilization of phosphate from intracellular to extracellular compartments. Consequently, the efficiency of modified bicarbonate conductivity to purify blood phosphate was tested. Methods Ten hemodialysis patients with chronic hyperphosphatemia (>2.1 mmol/L) were included in the two three–sessions‐per week periods. Bicarbonate concentration was fixed at 40 mmol/L and 30 mmol/L in the first and second periods, respectively. Phosphate depuration was evaluated by phosphate mobilization clearance (K_M). Findings Although bicarbonatemia was lower during the second period (21.0 ± 2.7 vs. 24.4 ± 3.1 mmol/L, P < 0.01), no difference was observed in phosphatemia (2.4 ± 0.5 vs. 2.3 ± 0.4 mmol/L, P = NS). The in‐session variation of phosphate was lower (?1.45 ± 0.42 vs. ?1.58 ± 0.44 mmol/L, P < 0.05) and K_M was higher during the second period (82.94 ± 38.00 vs. 69.74 ± 24.48 mL/min, P < 0.05). Discussion The decrease of in‐session phosphate and the increase in K_M reflect phosphate refilling during hemodialysis. Thus, modulation of serum bicarbonate may play a role in controlling the phosphate pool. Even though correcting metabolic acidosis during hemodialysis remains important, alkaline excess can impair phosphate mobilization clearance. Clinical trials are needed to test the efficiency and relevance of a strategy where bicarbonatemia is corrected less at the beginning of sessions.     

Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin‐free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding. Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring. Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high‐flux dialyzer F40, Fresenius): (1) 17‐year‐old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra‐cerebral hemorrhage (2 sessions); (2) 13‐year‐old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7‐year‐old boy (hyperoxaluria, access via PermCath^® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post‐dialyzer extracorporeal serum Ca⁺⁺ (aim < 0.3 mmol/L) and pre‐dialyzer intra‐corporeal Ca⁺⁺ (aim > 0.9) were measured for every 30 min. Serum Na⁺, K⁺, base excess (BE), blood flow, blood pressure, heart rate, and blood out‐flow and in‐flow pressure were also monitored. Results: For adequate RCA (mean extracorporeal serum Ca⁺⁺ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra‐corporeal Ca⁺⁺ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra‐corporeal ACT 90 ± 12 sec. Serum Na⁺, K⁺, and BE during HD were 138 ± 2, 3.5 ± 0.3, and ?0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca⁺⁺ < 0.6 mmol/L) cured by stopping dialysis. Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.     

The source of net ultrafiltration during hemodialysis is mostly the extracellular space regardless of hydration status

Fluid shifts are common in patients undergoing chronic hemodialysis (HD) during the intradialytic periods, as several liters of fluid are removed during ultrafiltration (UF). Some patients have experienced frequent intradialytic hypotension (IDH). However, the characteristics of fluid shifts and which fluid space is affected remain controversial. Therefore, we designed this study to evaluate the fluid spaces most affected by UF and to determine whether hydration status influences the fluid shifts during HD. This was a prospective cohort study of 40 patients undergoing HD. We measured the patient's fluid spaces using a whole‐body bioimpedance apparatus to evaluate the changes in the fluid spaces before HD and 1–4 hours of HD and 30 minutes after HD. UF achieved during HD by the 40 patients (age, 60.0 ± 5.2 years; 50% men; 50% of patients with diabetes; body weight, 61.3 ± 10.5 kg) was 2.18 ± 0.78 L (measured fluid overload, 2.15 ± 1.24 L). 1) Mean relative reduction of total body water and extracellular water was reduced from the start to the end of HD. 2) However, mean relative reduction of intracellular water was not reduced from the start to the end of HD. 3) No significant differences in fluid shifts were observed according to hydration status. The source of net UF during HD is mostly the extracellular space regardless of hydration status. Thus, IDH may be related to differences in the interstitial fluid shift to the vascular space.     

Survival with short‐daily hemodialysis: Association of time,site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.     

Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel

Control of hyperphosphatemia is a major goal in patients with end‐stage renal disease. However, removal of retained inorganic phosphorus during hemodialysis remains a major problem. We compared clearances and total phosphate removal in large patients treated with two F‐80 dialyzers (Fresenius Medical Care of North America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed with a single F‐80 dialyzer (SD). Clearances were obtained using total dialysate collections. Eight dialysate collections (5 patients) using double parallel dialyzers (DD group) were compared with 5 dialysate collections (4 patients) using single dialyzers (SD group). Blood and dialysate flow rates and time of dialysis treatment were identical between the groups. The DD group's Kt/V _urea was 1.46 ± 0.13; SD group's Kt/V _urea was 1.35 ± 0.09 (p = 0.2). Absolute phosphorus removal was 1594 ± 300 mg for the DD group, compared to 1108 ± 285 mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 ± 25 mL/minute and 251 ± 27 mL/ min in the SD group (p = 0.082). Phosphorus clearance was 178 ± 32 mL/min in the DD group and 149 ± 38 mL/min in the SD group (p = 0.039). There was no correlation between phosphorus clearance and dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2 hours of hemodialysis. This finding is consistent with the hypothesis that there are at least two pools of body phosphorus. Using hemodialyzers placed in parallel led to higher phosphate clearance and total phosphorus removal. This higher phosphate removal may be related in part to increasing the concentration gradient for transfer out of a second compartment.     

Quotidian dialysis Survival in 221 patients treated by short daily hemodialysis for 315 patient years

Scanty data suggests that large solutes show a kinetic behavior that is different from urea. The question investigated in this study is whether other small water‐soluble solutes such as some guanidino compounds show a kinetic behavior comparable or dissimilar to that of urea. This study included 7 stable conventional hemodialysis patients without residual diuresis undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet blood lines before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two‐pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V₁), the total distribution volume (V_tot), and the inter‐compartmental clearance (K₁₂); solute generation and ultrafiltration were determined independently. No significant differences were observed between V₁ and K₁₂ for urea (6.4 ± 3.3 L and 822 ± 345 mL/min) and for the guanidino compounds. However, with respect to V_tot, GSA was distributed in a smaller volume (30.6 ± 4.2 L) compared to urea (42.7 ± 6.0 L ? P < 0.001), while CTN, CT, GAA, G, and MG showed significantly larger volumes (54.0 ± 5.9 L, 98.0 ± 52.3 L, 123.8 ± 66.9 L, 89.7 ± 21.4 L, and 102.6 ± 33.9 L, respectively). These differences resulted in markedly divergent effective solute removal: 67%(urea), 58%(CTN), 42%(CT), 76%(GSA), 37%(GAA), 43%(G), and 42%(MG). In conclusion, the kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water‐soluble like urea.     

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.     

A simple and sensitive method for determination of vitamins D3 and K1 in rat plasma: application for an in vivo pharmacokinetic study

Purpose: To develop and to validate a simple but sensitive method for determination of vitamins D₃ and K₁ in rat plasma.

Methods: The sample treatment included protein precipitation by cold acetonitrile, evaporation, reconstitution with methanol and filtration. The chromatography conditions included Xterra RP18 3.5?µm 4.6?×?100?mm column at ambient temperature and mobile phase consisting of methanol/water (93/7, v/v) at 0.5?mL/min flow rate. Vitamin D₃ and probucol were detected at 265?nm and vitamin K₁ at 239?nm. Rats were administered intravenously by 0.1?mg/kg of vitamin D₃ or K₁ and the blood samples were withdrawn pre-administration and at pre-determined time points post-administration. The pharmacokinetic analysis was performed using a non-compartmental approach.

Results: The calibration curves in rat plasma were linear up to 5000?ng/mL for both vitamins. The limit of quantification (LOQ) was 20?ng/mL for vitamin D₃ and 40?ng/mL for K₁. Inter- and intra-day precision and accuracy were below 15%. The pharmacokinetic parameters of vitamin D₃ following intravenous administration were: AUC_0?∞?=?11323?±?1081?h?×?ng/mL, V_d?=?218?±?80?mL/kg, CL?=?8.9?±?0.8?mL/h/kg, t_1/2?=?16.8?±?5?h; and of vitamin K₁: AUC_0?∞?=?2495?±?297?h?×?ng/mL, V_d?=?60?±24?mL/kg, CL?=?40.5?±?5.1?mL/h/kg, t_1/2?=?1.1?±0.5?h.

Conclusion: The developed HPLC–UV assay is a simple and sensitive method for the determination of vitamins D₃ and K₁ in rat plasma. A higher dose of vitamin K₁ should be used in future studies for accurate estimation of pharmacokinetic parameters. The data show the suitability of the assay for pharmacokinetic studies in rats.     

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LA_max, LA_short, LA_long. LAVI was calculated due to formula: LAVI = (π/6X [LA_max × LA_short × LA_long])/m². LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m²). The calculated cutoff value of LAVI was 36.32 mL/m². In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.     

Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof‐of‐concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti‐Xa activity during hemodialysis (HD) sessions using a new heparin‐grafted HD membrane. In 45 stable HD patients, the use of a heparin‐grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse‐back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti‐Xa activity by 50%. Dose reductions were achieved with both types of heparin (low‐molecular‐weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti‐Xa activity at dialysis session end (low‐molecular‐weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti‐Xa activity at the end of HD sessions was possible in stable HD patients using heparin‐grafted membrane. HD patients who require low anti‐Xa activity at the end of HD sessions might benefit from a heparin‐grafted membrane to reduce bleeding risk and other heparin adverse events.     

Effect of a single hemodialysis session on inflammatory markers

Inflammation is a common feature of end-stage renal disease. Although there is evidence for hemodialysis (HD)-induced inflammatory process, the effect of a dialysis session on changes in inflammatory markers is still unclear. Seventeen patients of end-stage renal disease on maintenance HD along with 20 age-matched and sex-matched healthy controls were recruited after informed consent. C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (LpPLA2) activity were measured in the study and control groups. Intradialytic in CRP and LpPLA2 were studied. Comparison of pre-HD vs. the control group and predialytic and postdialytic values was performed using the Mann-Whitney U test and Wilcoxon's test, respectively. Statistical evaluation of intradialytic changes in inflammatory markers was performed using Friedman's test. Hemodialysis patients had higher CRP levels compared with controls (P=0.001). Post-HD LpPLA2 activity (n=17) was higher (P=0.039) compared with the pre-HD activity. Intradialytic changes in inflammatory markers showed a significant increase (P=0.012) in LpPLA2 activity (n=7), while no change (P=0.133) was observed in CRP levels (n=17). Evidence on the pro-inflammatory state being initiated by dialysis is provided by increased LpPLA2 activity. This may add to the atherogenic mileu and cause endothelial dysfunction in this high-risk group. Drugs that inhibit the LpPLA2 pathway have been developed and may be effective in these patients.