Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The dialyzer mass transfer-area coefficient (KoA) for urea is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = ~5/model, total N = 107) in vitro at 37°C for three countercurrent blood (Qb) and dialysate (Qd) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea KoA values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea KoA was similar for each. Urea KoA did not change (690 ± 160 vs. 680 ± 140 ml/min, P = NS) when Qb increased from 306 ± 7 to 459 ± 10ml/min at a nominal Qd of 500ml/min. When Qd increased from 504 ± 6 to 819 ± 8ml/min at a nominal Qb of 450ml/min, however, urea KoA increased (P < 0.001) by 14 ± 7% (range 3 to 33%, depending on the dialyzer model) to 780 ± 150ml/min. These data demonstrate that increasing nominal Qd from 500 to 800ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in urea clearance than predicted assuming a constant KoA

Relationship between volume status and blood pressure during chronic hemodialysis

Relationship between volume status and blood pressure during chronic hemodialysis.BackgroundThe relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial.MethodsWe determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N = 468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD.ResultsPredialysis systolic and diastolic BP values were 153.1 ± 24.7 (mean ± SD) and 81.7 ± 14.8mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 ± 22.7 and 73.9 ± 13.6mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 ± 1.3kg and plasma volume was contracted by 10.1 ± 9.5%. Multiple linear regression analyses showed that eachkg reduction in body weight during HD was associated with a 2.95mm Hg (P = 0.004) and a 1.65mm Hg (P = NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50mm Hg (P = 0.026) and a 2.56mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP.ConclusionsHD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload

Interplay between SIN3A and STAT3 Mediates Chromatin Conformational Changes and GFAP Expression during Cellular Differentiation

BACKGROUND: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis. The mechanisms of neural development underlying suppression and de-suppression of differentiation-related genes for cell fate specifications are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: By using an in vitro system in which NTera-2 cells were induced to differentiate into an astrocyte-like lineage, we revealed a novel role for Sin3A in maintaining the suppression of GFAP in NTera-2 cells. Sin3A coupled with MeCP2 bound to the GFAP promoter and their occupancies were correlated with repression of GFAP transcription. The repression by Sin3A and MeCP2 may be an essential mechanism underlying the inhibition of cell differentiation. Upon commitment toward an astrocyte-like lineage, Sin3A- MeCP2 departed from the promoter and activated STAT3 simultaneously bound to the promoter and exon 1 of GFAP; meanwhile, olig2 was exported from nuclei to the cytoplasm. This suggested that a three-dimensional or higher-order structure was provoked by STAT3 binding between the promoter and proximal coding regions. STAT3 then recruited CBP/p300 to exon 1 and targeted the promoter for histone H3K9 and H3K14 acetylation. The CBP/p300-mediated histone modification further facilitates chromatin remodeling, thereby enhancing H3K4 trimethylation and recruitment of RNA polymerase II to activate GFAP gene transcription. CONCLUSIONS/SIGNIFICANCE: These results provide evidence that exchange of repressor and activator complexes and epigenetic modifications are critical strategies for cellular differentiation and lineage-specific gene expression

Effect of Treatment Duration and Frequency on Uremic Solute Kinetics, Clearances and Concentrations

The kinetics of uremic solute clearances are discussed based on two categories of uremic solutes, namely those that are and those that are not derived directly from nutrient intake, particularly dietary protein intake. This review highlights dialysis treatments that are more frequent and longer (high-dose hemodialysis) than conventional thrice weekly therapy. It is proposed that the dialysis dose measures based on urea as a marker uremic solute, such as Kt/V and stdKt/V, be referred to as measures of dialysis inadequacy, not dialysis adequacy. For uremic solutes derived directly from nutrient intake, it is suggested that inorganic phosphorus and protein-bound uremic solutes be considered as markers in the development of alternative measures of dialysis dose for high-dose hemodialysis prescriptions. As the current gap in understanding the detailed kinetics of protein-bound uremic solutes, it is proposed that normalization of serum phosphorus concentration with a minimum (or preferably without a) need for oral-phosphorus binders be targeted as a measure of dialysis adequacy in high-dose hemodialysis. For large uremic solutes not derived directly from nutrient intake (middle molecules), use of extracorporeal clearances for β2 -microglobulin that are higher than currently available during thrice weekly therapy is unlikely to reduce predialysis serum β2 -microglobulin concentrations. High-dose hemodialysis prescriptions will lead to reductions in predialysis serum β2 -microglobulin concentrations, but such reductions are also limited by significant residual kidney clearance. Kinetic data regarding middle molecules larger than β2 -microglobulin are scarce; additional studies on such uremic solutes are of high interest to better understand improved methods for prescribing high-dose hemodialysis prescriptions to improve patient outcomes.status: publishe

Mathematical modelling of bicarbonate supplementation and acid-base chemistry in kidney failure patients on hemodialysis.

Acid-base regulation by the kidneys is largely missing in end-stage renal disease patients undergoing hemodialysis (HD). Bicarbonate is added to the dialysis fluid during HD to replenish the buffers in the body and neutralize interdialytic acid accumulation. Predicting HD outcomes with mathematical models can help select the optimal patient-specific dialysate composition, but the kinetics of bicarbonate are difficult to quantify, because of the many factors involved in the regulation of the bicarbonate buffer in bodily fluids. We implemented a mathematical model of dissolved CO2 and bicarbonate transport that describes the changes in acid-base equilibrium induced by HD to assess the kinetics of bicarbonate, dissolved CO2, and other buffers not only in plasma but also in erythrocytes, interstitial fluid, and tissue cells; the model also includes respiratory control over the partial pressures of CO2 and oxygen. Clinical data were used to fit the model and identify missing parameters used in theoretical simulations. Our results demonstrate the feasibility of the model in describing the changes to acid-base homeostasis typical of HD, and highlight the importance of respiratory regulation during HD

Automated peritoneal dialysis prescriptions for enhancing sodium and fluid removal: a predictive analysis of optimized, patient-specific dwell times for the day period

BACKGROUND: Remaining edema-free is a challenge for many automated peritoneal dialysis (APD) patients, especially those with fast ( high ) transport characteristics. Although increased use of peritoneal dialysis (PD) solutions with high glucose concentrations may improve volume control, frequent use of such solutions is undesirable. METHODS: We used the 3-pore kinetic model to evaluate 4 alternative therapy prescriptions for the APD day exchange in anuric patients with high, high-average, and low-average transport characteristics. Four prescriptions were modeled: Therapy 1: Optimal, individualized dwell times with a dry period. Therapy 2: Use of a midday exchange. Therapy 3: Use of an icodextrin-containing dialysate during a 14-hour dwell. Therapy 4: Use of optimal, individualized dwell times, followed by an icodextrin dwell to complete the daytime period. The alternative therapies were compared with a reference standard therapy using glucose solution during a 14-hour dwell. The nighttime prescription was identical in all cases (10 L over 10 hours), and all glucose solutions contained 2.27% glucose. Net ultrafiltration (UF), sodium removal (NaR), total carbohydrate (CHO) absorption, and weekly urea Kt/V for a 24-hour period were computed and compared. RESULTS: The UF and NaR were substantially higher with therapy 1 than with standard therapy (1034 mL vs 621 mL and 96 mmol vs 51 mmol respectively), without significant changes in CHO absorption or urea Kt/V. However, therapy 1 resulted in reduced β2-microglobulin clearance (0.74 mL/min vs 0.89 mL/min with standard therapy). Compared with therapy 1, therapy 2 improved UF and NaR (1062 mL vs 1034 mL and 99 mmol vs 96 mmol); however, that improvement is likely not clinically significant. Therapy 2 also resulted in a higher Kt/V (2.07 vs 1.72), but at the expense of higher glucose absorption (difference: 42 g). The UF and NaR were highest with a long icodextrin-containing daytime dwell either preceded by a short optimized dwell (1426 mL and 155 mmol) or without such a dwell (1327 mL and 148 mmol). CONCLUSIONS: The 3-pore model predictions revealed that patient-specific optimal dwell times and regimens with a longer day dwell might provide improved UF and NaR options in APD patients with a variety of peritoneal membrane transport characteristics. In patients without access to icodextrin, therapy 1 might enhance UF and NaR and provide a short-term option to increase fluid removal. Although that approach may offer clinicians a therapeutic option for the overhydrated patient who requires increased UF in the short term, APD prescriptions including icodextrin provide a means to augment sodium and fluid removal. Data from clinical trials are needed to confirm the predictions from this study

Intermittent peritoneal dialysis: urea kinetic modeling and implications of residual kidney function

BACKGROUND: Intermittent peritoneal dialysis (IPD) is an old strategy that has generally been eclipsed, in the home setting, by daily peritoneal therapies. However, for a select group of patients with exhausted vascular access or inability to receive PD at home, in-center IPD may remain an option or may serve as an incremental strategy before initiation of full-dose PD. We investigated the residual kidney clearance requirements necessary to allow thrice-weekly IPD regimens to meet current adequacy targets. METHODS: The 3-pore model of peritoneal transport was used to examine 2 thrice-weekly IPD dialysis modalities: 5 - 6 dwells with 10 - 12 L total volume (low-dose IPD), and 50% tidal with 20 - 24 L total volume (high-dose IPD). We assumed an 8-hour dialysis duration and 1.5% dextrose solution, with a 2-L fill volume, except in tidal mode. The PD Adequest application (version 2.0: Baxter Healthcare Corporation, Deerfield, IL, USA) and typical patient kinetic parameters derived from a large dataset [data on file from Treatment Adequacy Review for Gaining Enhanced Therapy (Baxter Healthcare Corporation)] were used to model urea clearances. The minimum glomerular filtration rate (GFR) required to achieve a total weekly urea Kt/V of 1.7 was calculated. RESULTS: In the absence of any dialysis, the minimum residual GFR necessary to achieve a weekly urea Kt/V of 1.7 was 9.7 mL/min/1.73 m(2). Depending on membrane transport type, the low-dose IPD modality met urea clearance targets for patients with a GFR between 6.0 mL/min/1.73 m(2) and 7.6 mL/min/1.73 m(2). Similarly, the high-dose IPD modality met the urea clearance target for patients with a GFR between 4.7 mL/min/1.73 m(2) and 6.5 mL/min/1.73 m(2). CONCLUSIONS: In patients with residual GFR of at least 7.6 mL/min/1.73 m(2), thrice-weekly low-dose IPD (10 L) achieved a Kt/V urea of 1.7 across all transport types. Increasing the IPD volume resulted in a decreased residual GFR requirement of 4.7 mL/min/1.73 m(2) (24 L, 50% tidal). In patients with residual kidney function and dietary compliance, IPD may be a viable strategy in certain clinical situations