Search

Removal of protein-bound uremic toxins (PBUTs) during conventional dialysis is insufficient. PBUTs are associated with comorbidities and mortality in dialysis patients. Albumin is the primary carrier for PBUTs and only a small free fraction of PBUTs are dialyzable. In the past, we proposed a novel method where a binding competitor is infused upstream of a dialyzer into an extracorporeal circuit. The competitor competes with PBUTs for their binding sites on albumin and increases the free PBUT fraction. Essentially, binding competitor-augmented hemodialysis is a reactive membrane separation technique and is a paradigm shift from conventional dialysis therapies. The proposed method has been tested in silico, ex vivo, and in vivo, and has proven to be very effective in all scenarios. In an ex vivo study and a proof-of-concept clinical study with 18 patients, ibuprofen was used as a binding competitor; however, chronic ibuprofen infusion may affect residual kidney function. Binding competition with free fatty acids significantly improved PBUT removal in pre-clinical rat models. Based on in silico analysis, tryptophan can also be used as a binding competitor; importantly, fatty acids or tryptophan may have salutary effects in HD patients. More chemoinformatics research, pre-clinical, and clinical studies are required to identify ideal binding competitors before routine clinical use.

An assessment of fluid status can be obtained by monitoring relative blood volume (RBV) during hemodialysis (HD) treatment. The dynamics of RBV is determined by fluid removal from the intravascular compartment by ultrafiltration (UF) and vascular refill from the interstitium. To characterize this dynamics, a two-compartment model describing the short-term dynamics of vascular refilling and UF is developed. Fluid movement between the compartments is governed by lymphatic and microvascular fluid shifts. Further, protein flux is described by convection, diffusion and the lymphatic protein flux. Patient specific parameters are identified based on hematocrit (Hct) measurements by the Crit-Line monitor (CLM). Different measurement frequencies and UF profiles are compared to determine data fidelity and influence on the quality of parameter estimates. This relevant information can be used to assess the (patho)physiological status of hemodialysis patients and could aid in individualizing therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Indoxyl sulfate is a protein-bound uremic toxin and its dialytic clearance is comparatively low. We propose a method to increase indoxyl sulfate dialytic clearance., Methods: Human serum albumin, preloaded with indoxyl sulfate, was circulated on the blood side of an F40S dialyzer with single-pass counter-current dialysate flow. Tryptophan or docosahexaenoic acid (DHA), which are binding competitors to indoxyl sulfate, were infused into the blood-side circuit upstream of the dialyzer, and their abilities to increase the removal of indoxyl sulfate determined., Results: Baseline indoxyl sulfate removal was 10.2 ± 0.3%, which increased to 18.5 ± 0.4% with infusion of tryptophan (p < 0.001) and 27.7 ± 1.0% with infusion of DHA (p < 0.001)., Conclusions: This study shows that tryptophan and DHA effectively increase indoxyl sulfate removal in an in vitro dialysis model. The concept of using binding competitors to enhance the clearance of protein-bound uremic toxins could be applied to current hemodialysis technology., (© 2015 S. Karger AG, Basel.)

Background: There is no agreement concerning dialyzate glucose concentration in hemodialysis (HD) and 100 and 200 mg/dL (G100 and G200) are frequently used. G200 may result in diffusive glucose flux into the patient, with consequent hyperglycemia and hyperinsulinism, and electrolyte alterations, in particular potassium (K) and phosphorus (P). This trial compared metabolic effects of G100 versus G200., Methods: Chronic HD patients participated in this randomized, single masked, controlled crossover trial (www.clinicaltrials.gov: #NCT00618033) consisting of two consecutive 3-week segments with G100 and G200, respectively. Intradialytic serum glucose (SG) and insulin concentrations (SI) were measured at 0, 30, 60, 120, 180, 240 min and immediately post-HD; P and K were measured at 0, 120, 180 min and post-HD. Hypoglycemia was defined as an SG<70 mg/dL. Mean SG and SI were computed as area under the curve divided by treatment time., Results: Fourteen diabetic and 15 non-diabetic subjects were studied. SG was significantly higher with G200 as compared to G100, both in diabetic {G200: 192.8±48.1 mg/dL; G100: 154.0±27.3 mg/dL; difference 38.8 [95% confidence interval (CI): 21.2-56.4] mg/dL; P<0.001} and non-diabetic subjects [G200: 127.0±11.2 mg/dL; G100 106.5±10.8 mg/dL; difference 20.6 (95% CI: 15.3-25.9) mg/dL; P<0.001]. SI was significantly higher with G200 in non-diabetic subjects. Frequency of hypoglycemia, P and K serum levels, interdialytic weight gain and adverse intradialytic events did not differ significantly between G100 and G200., Conclusion: G200 may exert unfavorable metabolic effects in chronic HD patients, in particular hyperglycemia and hyperinsulinism, the latter in non-diabetic subjects.

Background: Chronic hemodialysis (HD) patients suffer from an appallingly high cardiovascular mortality. During HD, patients are exposed to dialysate glucose, which may alter blood glucose levels and thus exert effects on the autonomic nervous system. Heart rate variability (HRV) is an established indicator of autonomic nervous system activity and a predictor of cardiovascular outcomes. This study investigated the effects of two commonly used dialysate glucose concentrations [100 mg/dl (HD100), and 200 mg/dl (HD200)] on HRV in chronic HD patients., Methods: In this prospective, randomized, controlled, single-masked, cross-over trial, subjects were randomized to receive HD100 or HD200 for a period of 3 weeks followed by a cross-over to the respective other dialysate (www.clinicaltrials.gov #NCT00618033). Blood glucose and insulin levels were measured before and after HD. Intradialytic Holter electrocardiograms were recorded and HRV time domain, frequency domain and complexity parameters analyzed., Results: Twenty-three HD patients (age 56 ± 12 years, 11 male, 14 black, 11 with diabetes) were studied. Diabetic subjects showed significantly higher serum glucose levels with HD200 as compared to HD100 (HD100: 146 ± 48 mg/dl; HD200: 192 ± 57 mg/dl; p < 0.01); this hyperglycemia was accompanied by an increase of the high-frequency band of HRV (p = 0.019), a reflection of increased parasympathetic activity. HRV did not change in nondiabetic subjects., Conclusion: In diabetic subjects, the use of HD200 increased vagal tone. Given the importance of sympathetic activation to counteract intradialytic hypotension, our findings support the use of HD100 in diabetic HD patients., (Copyright © 2011 S. Karger AG, Basel.)

The recently published KDIGO (Kidney Disease: Improvement of Global Outcomes) guideline (GL) for dialysate calcium suggests a narrow range of dialysate inlet calcium concentrations (C(di)Ca(++)) of 2.50-3.00 mEq/l. The work group's primary arguments supporting the GL were (1) there is a negligible flux of body Ca(++) during dialysis and (2) C(di)Ca(++) of 2.50 mEq/l will generally result in neutral Ca(++) mass balance (Ca(MB)). We believe we have shown that both of these arguments are incorrect. Kinetic modeling and analysis of dialyzer Ca(++) transport during dialysis (J(d)Ca(++)) demonstrates that more than 500 mg of Ca can be transferred during a single dialysis and that on average 76% of this Ca flux is from the miscible calcium pool rather than plasma pool. Kinetic modeling of intestinal calcium absorption (Ca(Abs)) shows a strong dependence of Ca(Abs) on the dose of vitamin D analogs and weaker dependence on the level of Ca intake (Ca(INT)). We used the Ca(Abs) model to calculate Ca(Abs) as a function of total Ca(INT) and prescribed doses of vitamin D analogs in 320 hemodialysis patients. We then calculated total dialyzer calcium removal (TJ(d)Ca(++)) and the C(di)Ca(++) that would be required to achieve TJ(d)Ca(++)=Ca(Abs), that is, Ca(MB)=0 over the whole dialysis cycle (that is, covering both the intra- and the inter-dialytic period). The results indicate that 70% of patients on Ca-based binders and 20-50% of patients on non-Ca-based binders would require C(di)Ca(++) <2.50 mEq/l to prevent long-term Ca accumulation.