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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.

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 ).

The three-pore model of peritoneal fluid transport predicts that once the osmotic gradient has dissipated, fluid reabsorption will be due to a combination of small-pore reabsorption driven by the intravascular oncotic pressure, and an underlying disappearance of fluid from the cavity by lymphatic drainage. Our study measured fluid transport by these pathways in the presence and absence of an osmotic gradient. Paired hypertonic and standard glucose-dwell studies were performed using radio-iodinated serum albumin as an intraperitoneal volume marker and changes in intraperitoneal sodium mass to determine small-pore versus transcellular fluid transport. Disappearance of iodinated albumin was considered to indicate lymphatic drainage. Variability in transcellular ultrafiltration was largely explained by the rate of small-solute transport across the membrane. In the absence of an osmotic gradient, fluid reabsorption occurred via the small-pore pathway, the rate being proportional to the small-solute transport characteristics of the membrane. In most cases, fluid removal from the peritoneal cavity by this pathway was faster than by lymphatic drainage. Our study shows that the three-pore model describes the pathways of peritoneal fluid transport well. In the presence of high solute transport, poor transcellular ultrafiltration was due to loss of the osmotic gradient and an enhanced small-pore reabsorption rate after this gradient dissipated.

The partitioning of fluid flows among small and ultrasmall pores of the three-pore model in peritoneal dialysis has been traditionally assessed using 4-hour dwells with 3.86% glucose solutions. Under these conditions, however, back-filtration through small pores has been hard to demonstrate. As nicely shown by Asghar and Davies, however, the use of low-concentration (1.36%) glucose-based solutions allows accurate studies of the partitioning of fluid flows from the peritoneal cavity under conditions of fluid loss.

The relationship between dialysis dose and nutrition is a field of particular interest in chronic pediatric dialysis (PD), and a positive correlation between ureaKt/V and nPNA has been published, suggesting a better nutritional status is associated with higher dialysis doses. However, this relationship has also been criticized as being the result of a mathematical coupling resulting from the same variables. The objective of the study was to establish the relationship between dialysis dose (Kt/V) and nutritional variables: daily protein intake (DPI), protein catabolic rate (PCR), protein equivalent of total nitrogen appearance (PNA) and nitrogen balance (NB) in dialyzed children. A cohort, prospective, observational study was carried out, for which 223 biochemical measurements were performed in 20 patients, ages 1 month to 14.3 years old (13 males), under PD for a 12-month period of follow-up. Monthly residual and total ureaKt/V, DPI, PCR, nPNA and NB were calculated, and the correlation between Kt/V and the nutritional parameters was evaluated. The Borah equation was used to calculate the nPNA. The data are reported as the mean plus or minus the standard error. All statistical comparisons were done with a paired t test, and two-way ANOVA for repeated measures was used to calculate correlations. A P <0.05 was considered significant. Mean total and residual Kt/V was 3.4+/-1.3 and 1.69+/-1.27, respectively; nPNA and PCR were 1.38+/-0.44 and 1.39+/-0.43 g/kg/day, daily protein intake (DPI) was 3.25+/-1.27 g/kg/day, and NB showed a value of 1.86+/-1.25 g/kg/day. A significant positive correlation was found between Kt/V and DPI, PCR, DPC and nPNA (all values P <0.0001), but no correlation was found between total and residual Kt/V vs. nitrogen balance ( P:ns). Total Kt/V showed a significant positive correlation with nPNA, but it did not show any correlation with nitrogen balance, suggesting that the relationship with nPNA is the result of a mathematical association calculated from the same variables.

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients. An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (Upwt2′). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and Upwt2′ (VID) are similar to those determined by the “gold standard” DDQ method (VDDQ). Eighty-two anuric hemodialysis patients were studied. VDDQ was 26.3 ± 5.2 L; VID was 26.5 ± 4.8 L. The (VID–VDDQ) difference was 0.2 ± 1.6 L, which is not statistically significant (P = 0.242). Anthropometric volume (VA) calculated using Watson equations was 33.6 ± 6.0 L. The (VA–VDDQ) difference was 7.3 ± 3.3 L, which is statistically significant (P < 0.001). Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.

Phosphate binders are necessary to control hyperphosphataemia in the majority of dialysis patients. Whilst aluminium salts are efficient phosphate binders, their use is associated with toxic side effects. Calcium salts are a widely used alternative, but hypercalcaemia is a common side effect, limiting their use and raising concern about metastatic calcification. Reduction of the dialysis fluid calcium concentration has been shown to reduce hypercalcaemia in haemodialysis patients, with an associated decrease in serum PTH. We analysed the effect of reduced calcium/magnesium (1.25/0.25 mmol/l), 40 mmol/l lactate, PD fluid (PD4) on 11 CAPD patients with uncontrollable hypercalcaemia ( > 2.65 mmol/l) and hyperphosphataemia ( > 1.80 mmol/l). Only 1 patient remained hypercalcaemic, while phosphate fell in 6 patients (2.23 ± 0.16 on no binder, to 1.68 ± 0.08 mmol/l at 6 months (p < 0.05), but was unchanged in 5 (2.10 ± 0.15 to 2.48 ± 0.14 mmol/l [p = NS]). Overall mean calcium × phosphate product changed little. However, in a subgroup it fell significantly (p < 0.05). Geometric mean iPTH rose, but not significantly. The subgroup of patients whose calcium × phosphate product fell, exhibited a much smaller rise in iPTH than the others (57.3-73.2 vs. 52.8-167.1 pg/ml). 1.25-Dihydroxyvitamin D 3 was subnormal in all patients. Mean serum magnesium fell from 1.24 ± 0.06 to 0.89 ± 0.04 mmol/l (p < 0.001), whilst mean serum bicarbonate rose significantly (25.2 ± 0.4 to 28.9 ± 1.2 mmol/l;p < 0.01). Withdrawal of aluminium-containing phosphate binders resulted in mean serum aluminium falling significantly from 31.1 ± 5.7 at start of PD4 to 15.4 ± 2.7 µg/l at 6 months (p < 0.05). In summary, in around 50% of CAPD patients with persistent hypercalcaemia and hyperphosphataemia, reduction in PD fluid calcium can produce significant improvement in phosphate, reduction of calcium × phosphate product, and enable avoidance of aluminium-containing phosphate binders. Patients whose calcium and phosphate control remains poor, still benefit from the reduction, or cessation, of oral aluminium intake.

Both the amount of dialysis and the size of the molecules removed may influence morbidity and mortality among patients receiving long-term hemodialysis. The multicenter Hemodialysis Study randomly assigned 1846 patients, according to a two-by-two factorial design, either to the standard dialysis dose currently recommended in the United States or to a high dialysis dose, with either a high-flux or a low-flux dialyzer. Neither mortality from any cause nor morbidity differed between the groups during a mean follow-up of 2.84 years. There was no major benefit from increasing the dialysis dose or from switching to high-flux membranes. Two treatment-related factors implicated in the substantial mortality and morbidity among patients undergoing maintenance hemodialysis 1 are the dose of dialysis delivered and the size of molecules removed. An index of the dialysis dose is the fractional clearance of urea (molecular mass, 60 D) which is commonly expressed as the intradialytic urea-reduction ratio 2 or as Kt/V, where K represents the rate of urea clearance by the dialyzer in milliliters per minute, t the duration in minutes of the treatment session, and V the volume of distribution of urea in the patient in milliliters. 3 Current guidelines in the United States target a . . .

To mitigate the risk of infection and disordered blood lipid metabolism, glucose-free dialysate is widely utilized in China and European countries. While glucose-free dialysis does not necessarily lead to hypoglycemia, several other metabolic adjustments must occur to maintain normal blood glucose levels. Additionally, glucose-free dialysis may also increase the loss of amino acids and the susceptibility to hypotension and cardiovascular events. Incorporating an appropriate amount of glucose into the dialysate can help to offset the insufficient blood glucose during hemodialysis (HD), potentially reducing the incidence of hypoglycemia. Currently, the efficacy and safety of glucose-containing dialysate during HD remain contentious, and this study will be conducted to evaluate the efficacy and safety of 5.5 mmol/L glucose-containing dialysate for maintenance HD patients. A multicenter, prospective, open-label, parallel-group, randomized controlled trial (RCT) will be conducted at more than 30 dialysis centers in China. Approximately 600 participants undergoing maintenance HD will be enrolled. Eligible patients will be randomly assigned to two groups, receiving either glucose-containing dialysate or glucose-free dialysate for HD at a 1:1 ratio, determined by a central computer-generated randomized sequence. The primary outcome is the incidence of the major cardiovascular and cerebrovascular adverse events (MACCE). Secondary outcomes are all-cause mortality, incidence of intradialytic hypotension (IDH), incidence of hypoglycemia, blood pressure and blood glucose variability, dysfunction of vascular access, cardiac function and fatigue level. Outcome assessors and data analysts will be blinded. All data will be analyzed using either intention-to-treat or per-protocol analysis methods. The results of this study will provide evidence on the efficacy and safety of 5.5 mmol/L glucose-containing dialysate for maintenance HD patients, and will provide valuable insights for future dialysate selection and the enhancement of dialysis treatment prescriptions. ChiCTR2400083153.