Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Evaluation of glycemic status during the days of hemodialysis using dialysis solutions with and without glucose.

Hypoglycemia has been documented during regular hemodialysis (HD) in both diabetic and nondiabetic end-stage renal disease (ESRD) patients. The aim of this study was to evaluate the glycemic fluctuations in diabetic and nondiabetic ESRD patients during HD days using glucose-free and glucose-containing dialysate. We conducted a prospective interventional study in which 32 ESRD patients (16 diabetic and 16 nondiabetic) were included in the study. All the patients underwent two HD sessions with glucose-free bicarbonate solution (phase 1) and next two HD sessions done with 100 mg/dL glucose-containing dialysate (phase 2). Serum glucose was measured using a continuous glucose monitoring system at the 1st h, 2nd h, and 4th h in both the phases. Percentage of time above and below preset target range (70-140 mg/dL) in 24 h on HD days in both phases was noted. Glucose loss in effluent fluid from dialyzer also was estimated at the 1st h, 2nd h, and 4th h. Statistical analysis was performed using Statistical Package for the Social Sciences software. Data are expressed as mean ± standard deviation. The Chi-square test was used for comparison of categorical variables. Continuous variables were compared using Student's t-test. Value of P <0.05 was considered statistically significant. With glucose-free dialysate solution, 20 patients (diabetic - 15, nondiabetic - 5) had 22 episodes of hypoglycemia in 64 sessions and with glucose-containing solution, only five patients (diabetic - 4, nondiabetic - 1) had five episodes of hypoglycemia (P = 0.002). For all patients, glucose lost (g/h) in the effluent fluid was at lower values in phase 2 (5.91 ± 1.5) when compared to phase 1 (7.08 ± 10.9) (P <0.0002). This was also observed both among the diabetic and nondiabetic patients. The mean percentage of time below target out of 24 h on HD days in phase 1 was significantly higher as against phase 2 (33% vs. 18.7%; P = 0.0001) which was observed both among diabetic group (18.65% vs. 13.5%; P = 0.03) and nondiabetic group (48.12 % vs. 23.4%; P = 0.0003); the mean percentage of time above the target (>140 mg/dL) out of 24 h on HD days was significantly higher than phase 2 (21.1% vs. 9.3%; P = 0.0001). This was also observed among diabetics group of patients (18.8% vs. 8.6 %; P = 0.0001). Most of this time above target occurred during the post HD period. However, in the nondiabetic group, there was no significant difference between the two phases. Glucose-containing dialysate at 100 mg/dL significantly reduced the hypoglycemic episodes and also the intensity of hypoglycemia. Diabetic patients dialyzed with glucose-free dialysate had increased time above target (akin to Somogyi effect) in the post HD period compared to same patients dialyzed with glucose-containing dialysate. Hence, glucose-containing dialysate appears to offer better glycemic control and lesser glycemic fluctuations during HD days for both diabetic and nondiabetic ESRD patients.

Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

INTRODUCTION: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. METHODS: Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. FINDINGS: The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. DISCUSSION: The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation.

BACKGROUND: In the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients. METHODS: The Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD. RESULTS: Data from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events. CONCLUSIONS: A small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on 11 Dec 2014 ( NCT02334267 ).

Solute and Water Transport in Peritoneal Dialysis: A Case-Based Primer.

Peritoneal dialysis (PD) is an effective therapy for patients with end-stage kidney disease. Dialysis solutions containing physiologic concentrations of electrolytes and base, as well as glucose often at supraphysiologic concentrations, are infused into the peritoneal cavity for solute and water exchange, and the patient's own peritoneal membrane is used for dialysis. The peritoneal membrane is dominated by small pores, which allow transport of water and small-molecular-size solutes, including electrolytes, by way of both diffusion and convection. Through small pores, diffusion allows the movement of solutes from the high-concentration compartment to a lower-concentration region. Also, through small pores, water and solutes move together by convection in response to an osmotic force. The glucose in the dialysis solution generates osmotic force to drive convection. In addition to small pores, the peritoneal membrane contains a specialized water channel, aquaporin 1, which is also present in capillaries of the peritoneal membrane. These specialized water channels, which are upregulated by glucose, allow water transport without solute (free water) in response to the osmotic force induced by glucose in the PD solution. During a PD exchange, net loss or gain of electrolytes and base is determined by both their gradient between capillary blood and dialysis solution and the net ultrafiltration volume. Developing a PD prescription, including the amount of glucose used, and changing the prescription in response to dietary changes and/or loss of residual kidney function requires a sound understanding of the peritoneal physiology. The case studies presented here help solidify the basic elements of PD prescription and how the PD prescription should be altered in response to changing clinical situations.

Phosphate Binders and Targets Over Decades: Do We have it Right Now?

In advanced renal disease, the kidney is unable to maintain phosphate balance due to decreased urinary excretion as well as the imbalance of the bone metabolic axis. It is well established that hyperphosphatemia is associated with increased cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, there are no randomized controlled trials that demonstrate a clear benefit on hard outcomes in lowering serum phosphate levels to recommended targets in the CKD or dialysis population. In addition, while calcium-based phosphate binders have traditionally been the standard of care in the treatment of hyperphosphatemia, data regarding the increased risk of vascular mineralization continues to emerge. Clinicians continue to search for new phosphate-lowering therapies as well as investigate novel nutritional perspectives. The Kidney Disease: Improving Global Outcomes is currently revising the guidelines on phosphate goals in CKD. This review will outline the history of phosphate targets and phosphate binders, and explore innovative phosphate-lowering therapies. Based on current data, clinicians moving forward should continue to treat end-stage renal disease patients with hyperphosphatemia based on individual risk factors for vascular mineralization.

Matrix metalloproteinase 9 is associated with peritoneal membrane solute transport and induces angiogenesis through ß-catenin signaling.

Background: For patients using peritoneal dialysis (PD), the peritoneal membrane can develop fibrosis and angiogenesis, leading to ultrafiltration failure, chronic hypervolemia and increased risk of technique failure and mortality. Matrix metalloproteinases (MMPs), and specifically the gelatinases (MMP2 and MMP9), may be involved in peritoneal membrane injury. Methods: From stable PD patients, mesothelial cells were assayed for MMP gene expression. MMP9 was overexpressed in mouse peritoneum by adenovirus, and MMP9 -/- mice were subjected to transforming growth factor ß (TGF-ß)-induced peritoneal fibrosis. Results: MMP9 mRNA expression correlated with peritoneal membrane solute transport properties. Overexpression of MMP9 in the mouse peritoneum induced submesothelial thickening and angiogenesis. MMP9 induced mesothelial cell transition to a myofibroblast phenotype measured by increased alpha smooth muscle actin and decreased E-cadherin expression. Angiogenesis was markedly reduced in MMP9 -/- mice treated with an adenovirus expressing active TGF-ß compared with wild-type mice. TGF-ß-mediated E-cadherin cleavage was MMP9 dependent, and E-cadherin cleavage led to ß-catenin-mediated signaling. A ß-catenin inhibitor blocked the angiogenic response induced by AdMMP9. Conclusions: Our data suggest that MMP9 is involved in peritoneal membrane injury possibly through cleavage of E-cadherin and induction of ß-catenin signaling. MMP9 is a potential biomarker for peritoneal membrane injury and is a therapeutic target to protect the peritoneal membrane in PD patients.

Individualizing the dialysate calcium concentration.

PURPOSE OF REVIEW: The optimal dialysate calcium concentration (DCC) in hemodialysis patients is still debated. Strategies have varied over time due to developments in the treatments available for mineral metabolism disorders and our increasing knowledge of bone and vascular diseases. International recommendations [Kidney Disease Outcomes Quality Initiative (KDIGO) and European Best Practice Guidelines] urge for DCC individualization in order to meet the patient's specific needs whenever possible. In this review, we aim to discuss the pros and cons of individualizing the DCC in hemodialysis patients. RECENT FINDINGS: Different regions of the world have various strategies with respect to DCCs. Decreasing the DCC slightly reduces calcemia, but mainly stimulates parathyroid hormone secretion and bone turnover. Conversely, increasing the DCC increases calcemia slightly and reduces parathyroid hormone secretion and bone turnover markedly. Furthermore, higher DCCs favor hemodynamic stability and can prevent ventricular arrhythmias. The impact of DCC individualization on survival rate or cardiovascular calcification progression has not been evaluated. SUMMARY: Individualizing DCC appears to be useful but requires time, a clear defined strategy, and close biological monitoring. Even though some studies have shown that using individualized DCCs of 1.25 or 1.75 mmol/l is not harmful, the real benefits of this strategy need to be assessed in a large, multicentric trial.

Dialysate content and risk of sudden cardiac death.

PURPOSE OF REVIEW: Although the overall mortality rate of patients with end-stage renal disease in the United States continues to decline, cardiac complications remain a leading cause of death in this population. The purpose of this review is to identify principles that can be used to optimize the dialysate concentration of electrolytes in order to reduce the incidence of sudden cardiac deaths (SCDs). RECENT FINDINGS: The ratio of observed to expected SCD is 1.71 in the 12 h following the onset of a hemodialysis session. A dialysate potassium concentration of less than 2 mEq/l has been associated with an increased risk of SCD as has a dialysate calcium less than 2.5 mEq/l and an elevated serum to dialysate calcium gradient. Midweek predialysis serum bicarbonate concentrations that are less than 22 or more than 27 mEq/l have been associated with increased mortality. An elevated predialysis serum bicarbonate may be a sign of the malnutrition inflammation complex syndrome. Magnesium has not been well studied in hemodialysis patients. SUMMARY: Dialysate content plays an important role in the risk of SCD in hemodialysis patients on hemodialysis. There is a need for further studies designed to identify patients at risk and to determine what strategies can be used to lower this risk.

Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of Mathematical Modeling.

Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2-2-3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one-compartment model was applied to describe the profile of phosphate in blood serum during intra- and interdialytic periods of 1-week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (KM ) and the rate of phosphate mobilization (RM ), were correlated with the reduction of serum phosphate concentration during dialysis (Cpost /Cpre ) and with equivalent continuous clearance (ECC) for phosphate. KM correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between RM and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one-compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one-compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate.

Effects of lowering dialysate calcium concentration on mineral metabolism and hemodynamic parameters in hemodialysis patients.

INTRODUCTION: It has been suggested that a dialysate calcium concentration of 1.5 mmol/L is a compromise between bone protection and cardiovascular risk. This study aimed to investigate the effect of reducing dialysate calcium concentration to 1.5 mmol/L on mineral metabolism and hemodynamic parameters. MATERIALS AND METHODS: Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5 mmol/L for 9 months and observed the effects on mineral metabolism and dialysis outcome parameters in 52 hemodialysis patients. RESULTS: The results at 9 months demonstrated that postdialytic serum calcium level decreased significantly from 109 ± 7 mg/L to 102 ± 6 mg/L, intact parathyroid hormone (PTH) increased from 372 ± 52 pg/mL to 606 ± 80 pg/mL, and the oral alfacalcidol increased from 1.4 ± 0.3 µg/w to 3.3 ± 0.4 µg/w. In patients with low PTH levels, continuous increase of PTH was observed. There were no significant variation in the oral calcium carbonate dose and serum levels of alkaline phosphatase, predialytic calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and postdialysis systolic blood pressure were significantly lower after reducing the dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and cramps were more frequent with this dialysate calcium concentration. CONCLUSIONS: These findings demonstrated that a decrease in dialysate calcium concentration from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of postdialytic hypercalcemia and releasing oversuppression of PTH, but it was associated with more use of oral alfacalcidol and more hemodynamic impairment.

Líquido dializante con citrato frente a acetato en pacientes en hemodiafiltración on-line de alta eficacia: parámetros a estudio / Citrate- versus acetate- based dialysate in patients in high-efficiency online hemodiafiltration: parameters to be studied

Introducción: El líquido dializante con acetato se reporta menos biocompatible, generando estrés oxidativo e inflamación. Entre los beneficios asociados al citrato destacan sus propiedades antiinflamatorias y antioxidantes, poder anticoagulante, quelante del calcio iónico, efecto tampón y mejora la tolerancia a la sesión. Objetivo: Comparar parámetros nutricionales e inflamatorios, eficacia dialítica, estatus ácido-base, tolerancia y balance de calcio en hemodiafiltración en línea empleando líquido dializante con citrato frente a líquido dializante con acetato. Material y métodos: Estudio prospectivo cruzado sobre población en hemodiafiltración en línea de 24 semanas. Inician 35 pacientes (finalizan 33), con 57,4 años, 55% hombres, 54,1 meses de permanencia. 79% portadores de fistula arteriovenosa. Se analizan 2376 sesiones. El estudio tiene dos fases. Variables: albúmina, PCR, Beta 2 microglobulinas (B2MCG), ángulo de fase (AF), masa celular corporal (BCM), Kt, volumen de reinfusión, PTTA, tiempo de hemostasia, estado de cámaras y dializador, pH, bicarbonato, calcio iónico, sesiones con hipotensión y calambres. Análisis estadístico SPSS 13.0. Contraste de hipótesis mediante T-Student y W de Wilcoxon para variables cuantitativas. Chi-cuadrado cualitativas. Significación estadística p<0,05. Resultados: Diferencias significativas (p<0,001) en albúmina, PCR, y B2MCG. BCM (p=0,001), AF (p=0,002) y Kt (p< 0,001) mayores con líquido de diálisis con citrato. Bicarbonato postdiálisis menor (p<0,001) con líquido de diálisis con citrato. Calcio iónico pre y postdiálisis (p=0,007 y p<0,001 respectivamente) menores con líquido de diálisis con citrato. Conclusiones: La diálisis con citrato se muestra en nuestra serie más biocompatible y con menor inflamación, mejora los parámetros nutricionales analíticos y por impedancia e incrementa la eficacia dialítica. Reduce el bicarbonato postdiálisis. Tanto pre como postdiálisis el calcio iónico es menor, permaneciendo estable (AU)

Introduction: Liquid dialysate with acetate (LDA) reported less biocompatible, generating oxidative stress and inflammation. Perceived benefits include its anti-inflammatory citrate buffer effect and antioxidant properties, anticoagulant power, chelating ionized calcium, and improves tolerance to the session. Objective: To compare nutritional and inflammatory parameters, dialysis efficiency, acid-base status, tolerance and calcium balance in on-line hemodiafiltration (OL-HDF) using citrate dialysate (LDC) versus LDA. Methods: Prospective cross OLHDF population in 24 weeks. Begins 35 patients (33 finish), with 57.4 years, 55% male, 54.1 months of permanence. 79% carriers arteriovenous fistula. 2376 sessions are analyzed. The study has two phases. Variables: albumin, CRP, Beta 2 microglobulin (B2MCG), phase angle (PA), body cell mass (BCM), Kt, reinfusion volume, PTTA, hemostasis time, state cameras and dialyzer, pH, bicarbonate, calcium ion, sessions with hypotension and cramps. Statistical analysis SPSS 13.0. Hypothesis testing using T-Student and Wilcoxon W for quantitative variables. Chi-squared qualitative. Statistical significance p <0.05. Results: Significant differences (p <0.001) in albumin, CRP, and B2MCG. BCM (p = 0.001), AF (p = 0.002) and Kt (p <0.001) higher with LDC. Lower post-dialysis bicarbonate (p <0.001) with LDC. Calcium ion pre and post-dialysis (p = 0.007 and p <0.001 respectively) with lower LDC. Conclusion: Dialysis citrate shown in our series more biocompatible and less inflammation, improves nutritional parameters and analytical impedance and increases efficiency dialysis. Reduces post-dialysis bicarbonate. Both pre-and post-dialysis ionized calcium is lower, remaining sta (AU)

La respuesta a darbepoetina-alfa está modulada por el binomio nutrición inflamación en pacientes en hemodiálisis / Darbepoetin-alpha responsiveness is modulated by malnutrition-inflammation binomial in hemodialysis patients

La anemia es un desorden multifactorial que aumenta la mortalidad en pacientes en hemodiálisis (HD). El objetivo del estudio fue investigar la relación entre el índice de resistencia a la eritropoyesis (IRE) con marcadores nutricionales-inflamatorios, y analizar si estos factores modulaban la respuesta a darbepoetina-alfa en 60 pacientes en HD. La muestra fue clasificada en terciles (Tn) de IRE: respondedores (T1), respondedores intermedios (T2), e hiporrespondedores (T3). La hiporrespuesta a darbepoetina-alfa se relacionó con depleción de la masa muscular, hipoalbuminemia y síndrome de malnutrición-inflamación. La proteína C-reactiva, escala de malnutrición-inflamación y la prealbúmina sérica (P<0,05) fueron predictores independiente del IRE. La respuesta a darbepoetina-alfa está modulada, entre otros factores, por el binomio nutrición-inflamación elevando considerablemente el coste sanitario en pacientes en HD

Anemia is a multifactorial disorder which increases mortality in hemodialysis patients (HD). The aim of the study was to investigate the relationship between the erythropoiesis responsiveness index (ERI) with nutritional and inflammatory markers, and to analyze whether those factors modulating the response to darbepoetin-alpha in 60 HD patients. The sample was classified into ERI tertiles (Tn): responsiveness (T1), mild responsiveness (T2), hyporesponsiveness (T3). Hyporesponsiveness to darbepoetin-alpha was significantly associated with muscle wasting, lower serum albumin levels and malnutrition-inflammation. C-reactive protein, malnutrition-inflammation score, and serum prealbumin were independent predictors of the ERI (P<0.05). Responsiveness to darbepoetin-alpha is modulated by malnutrition-inflammation binomial which raises the cost-health in HD patients

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.

Dialysate interleukin-6 predicts increasing peritoneal solute transport rate in incident peritoneal dialysis patients.

BACKGROUND: Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. METHODS: The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). RESULTS: Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. CONCLUSION: Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis.

Estudio piloto comparativo de dos soluciones de sellado en catéteres de hemodiálisis: heparina sódica al 5 por ciento frente a fibrilin® / Comparative pilot study of two haemodialysis catheter lock solutions: 5 percent heparin sodium compared to fibrilin®

El sellado de catéteres en hemodiálisis suele ser motivo de controversia entre los distintos profesionales dedicados a la hemodiálisis. El objetivo del presente estudio es comparar dos soluciones de sellado de catéter para hemodiálisis: heparina al 5% y fibrilin (heparina 20ui/ml + metil y propilparaben). Estudiamos 8 pacientes (mujeres) de 69±12 años portadoras de catéter tunelizado de 17±7 meses de duración del catéter, estables y que habían dado su consentimiento para el estudio. Inicialmente se selló con fibrilin durante un mes (12 sesiones) y posteriormente con heparina al 5% el mismo periodo de tiempo. Se registró velocidad de bomba, flujo efectivo, presión venosa, KT, necesidad de utilizar fibrinolíticos, infecciones, nº de manipulaciones, hipotensiones, recirculación, KT/V, TP, TPTA. Se compararon los estudios mediante t student. Después de dos meses de estudio se observó mayor flujo efectivo 318±23 ml/m en catéteres sellados con heparina frente a 307±17 ml/m con fibrilin (p= 0,008), menor presión venosa 147±12 mm Hg en heparina frente a 168±17 en fibrilin (p=0,006), mayor KT en heparina 43±3 litros frente a 41±4 litros en fibrilin. A pesar de estas mejores condiciones, clínicamente no supusieron diferencias en la eficacia dialítica KT/V heparina 1,56±0,2 frente a 1,59 ±0,2 en fibrilin. Si se observó un mayor nº de manipulaciones del catéter en heparina 12±0,2 frente a 9,4±1,3 en fibrilin (p=0,001). No existieron diferencias en aparición de infecciones, recirculación, necesidad de fi brinoliticos o alteraciones de coagulación. Concluimos que el sellado de catéteres de Hemodiálisis con Fibrilin es una alternativa eficaz a la heparina al 5%. No se acompaña de un mayor grado de disfunción del catéter y si de un menor nº de manipulaciones, lo que podría condicionar un menor nº de infecciones asociado a catéteres(AU)

Catheter locks in haemodialysis are usually a source of controversy among the different professionals involved in haemodialysis. The aim of this study is to compare two haemodialysis catheter lock solutions: 5% heparin and fibrilin (heparin 20ui/ml + methyl and propyl paraben). We studied 8 patients (women) aged 69±12 years with tunnelled catheters of 17±7 months’ duration, whose condition was stable and who had given their consent to the study. Initially, the fibrilin lock solution was used with the catheters for one month (12 sessions) and then 5% heparin for the same length of time. Pump speed, effective flow, venous pressure, KT, the need to use fibrinolytics, infections, number of handlings, hypotension episodes, recirculation, KT/V, TP, TPTA were measured. The results were compared using student’s t-test. After two months of study, a greater effective flow 318±23 ml/m was observed in catheters with heparin lock compared to 307±17 ml/m with fibrilin (p= 0.008), lower venous pressure 147±12 mm Hg in heparin compared to 168±17 in fibrilin (p=0,006), higher KT in heparin 43±3 litres compared to 41±4 litres in fibrilin. Despite these better conditions, they did not represent clinical differences in dialysis efficacy, KT/V heparin 1.56±0.2 compared to 1.59 ±0.2 in fibrilin. A higher number of catheter handlings was observed in heparin 12±0.2 compared to 9.4±1.3 in fibrilin (p=0.001). There were no differences in the appearance of infections, recirculation, need for fi brinolytics or coagulation alterations. We conclude that the use of fibrilin lock solution for haemodialysis catheters is an effective alternative to 5% heparin. It is not accompanied by a higher degree of catheter dysfunction but does involve less handling, which could lead to fewer catheter-associated infections(AU)

Dialysate calcium concentration and mineral metabolism in long and long-frequent hemodialysis: a systematic review and meta-analysis for a Canadian Society of Nephrology clinical practice guideline.

BACKGROUND: Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. STUDY DESIGN: Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. SETTING & POPULATION: Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. SELECTION CRITERIA FOR STUDIES: We included clinical trials, cohort studies, case series, case reports, and systematic reviews. INTERVENTIONS: Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. OUTCOMES: Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. RESULTS: 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. LIMITATIONS: Almost all the available information is related to changes in laboratory values and surrogate outcomes. CONCLUSIONS: Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.

The application of (-)-epigallocatechin gallate in preparation of an antioxidant dialysate.

Hemodialysis can remove uremic solutes but this treatment induces oxidative stress in uremic patients because of hemo-incompatibility. Therefore, we hypothesised that an antioxidant dialysate (a dialysate containing antioxidant(s)) would provide antioxidant defence in uremic patients during hemodialysis. Several herbal extracts were studied and measurements of antioxidant power and stability assays indicated that epigallocatechin gallate (EGCG) was the best of those tested for use as an antioxidant dialysate (EGCG dialysate). We observed that EGCG dialysate could provide the highest level of antioxidant defence at a dialysate flow rate of 500 ml/min and a blood flow rate of 200 ml/min. In addition, some important parameters for hemodialysis were calculated for supporting the protective role of EGCG dialysate. This is the first description of the preparation of an antioxidant dialysate. We suggest that EGCG dialysate will reduce the level of oxidative stress in hemodialysis patients, leading to a decrease of complications associated with oxidative damage.