@article{DevineKrieterRuethetal.2014, author = {Devine, Eric and Krieter, Detlef H. and R{\"u}th, Marieke and Jankovski, Joachim and Lemke, Horst-Dieter}, title = {Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate}, series = {Toxins}, volume = {6}, journal = {Toxins}, number = {2}, doi = {10.3390/toxins6020416}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117486}, pages = {416-429}, year = {2014}, abstract = {Protein binding prevents uremic toxins from removal by conventional extracorporeal therapies leading to accumulation in maintenance dialysis patients. Weakening of the protein binding may enhance the dialytic elimination of these toxins. In ultrafiltration and equilibrium dialysis experiments, different measures to modify the plasma binding affinity and capacity were tested: (i), increasing the sodium chloride (NaCl) concentration to achieve a higher ionic strength; (ii), increasing the temperature; and (iii), dilution. The effects on the dissociation constant K-D and the protein bound fraction of the prototypical uremic toxin indoxyl sulfate (IS) in plasma of healthy and uremic individuals were studied. Binding of IS corresponded to one site binding in normal plasma. K-D increased linearly with the NaCl concentration between 0.15 (K-D = 13.2 +/- 3.7 mu M) and 0.75 M (K-D = 56.2 +/- 2.0 mu M). Plasma dilution further reduced the protein bound toxin fraction by lowering the protein binding capacity of the plasma. Higher temperatures also decreased the protein bound fraction of IS in human plasma. Increasing the NaCl concentration was effective to weaken the binding of IS also in uremic plasma: the protein bound fraction decreased from 89\% +/- 3\% to 81\% +/- 3\% at 0.15 and 0.75 M NaCl, respectively. Dilution and increasing the ionic strength and temperature enhance the free fraction of IS allowing better removal of the substance during dialysis. Applied during clinical dialysis, this may have beneficial effects on the long-term outcome of maintenance dialysis patients.}, language = {en} } @article{KrieterRuethLemkeetal.2023, author = {Krieter, Detlef H. and R{\"u}th, Marieke and Lemke, Horst-Dieter and Wanner, Christoph}, title = {Clinical performance comparison of two medium cut-off dialyzers}, series = {Therapeutic Apheresis and Dialysis}, volume = {27}, journal = {Therapeutic Apheresis and Dialysis}, number = {2}, doi = {10.1111/1744-9987.13919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318643}, pages = {284 -- 292}, year = {2023}, abstract = {Introduction Medium-cut-off (MCO) dialyzers may beneficially impact outcomes in patients on hemodialysis. Methods In a randomized, controlled trial in maintenance hemodialysis patients, the new Nipro ELISIO-17HX MCO dialyzer was compared to the Baxter Theranova 400 filter regarding middle molecule removal. Furthermore, the suitability of two assays for free lambda-light chain (λFLC) detection (Freelite vs. N-Latex) was verified. Results ELISIO-HX achieved slightly lower reduction ratios for β2-microglobulin (71.8 ± 6.0 vs. 75.3 ± 5.8\%; p = 0.001), myoglobin (54.7 ± 8.6 vs. 64.9 ± 8.7\%; p < 0.001), and kappa-FLC (62.1 ± 8.8 vs. 56.3 ± 7.7\%; p = 0.021). λFLC reduction ratios were more conclusive with the Freelite assay and not different between ELISIO-HX and Theranova (28.4 ± 3.9 vs. 38.7 ± 13.4\%; p = 0.069). The albumin loss of Theranova was considerably higher (2.14 ± 0.45 vs. 0.77 ± 0.25 g; p = 0.001) and the Global Removal ScoreLoss alb largely inferior (30.6 ± 7.4 vs. 82.4 ± 29.2\%/g; p = 0.006) to ELISIO-HX. Conclusions The new ELISIO-HX expands the choice of dialyzers for MCO hemodialysis.}, language = {en} } @article{KrieterKerwagenRuethetal.2019, author = {Krieter, Detlef H. and Kerwagen, Simon and R{\"u}th, Marieke and Lemke, Horst-Dieter and Wanner, Christoph}, title = {Differences in dialysis efficacy have limited effects on protein-bound uremic toxins plasma levels over time}, series = {Toxins}, volume = {11}, journal = {Toxins}, number = {4}, doi = {10.3390/toxins11010047}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201770}, pages = {47}, year = {2019}, abstract = {The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta2-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta2-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term.}, language = {en} }