| 1. |
- Adoberg, Annika, et al.
(författare)
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Treatment with Paracetamol Can Interfere with the Intradialytic Optical Estimation in Spent Dialysate of Uric Acid but Not of Indoxyl Sulfate
- 2022
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Ingår i: Toxins. - : MDPI. - 2072-6651. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Optical online methods are used to monitor the haemodialysis treatment efficiency of end stage kidney disease (ESKD) patients. The aim of this study was to analyse the effect of the administration of UV-absorbing drugs, such as paracetamol (Par), on the accuracy of optical monitoring the removal of uremic toxins uric acid (UA) and indoxyl sulfate (IS) during standard haemodialysis (HD) and haemodiafiltration (HDF) treatments. Nine patients received Par in daily dosages 1-4 g for 30 sessions. For 137 sessions, in 36 patients the total daily dosage of UV-absorbing drugs was less than 500 mg, and for 6 sessions 3 patients received additional UV-absorbing drugs. Par administration slightly affected the accuracy of optically assessed removal of UA expressed as bias between optically and laboratory-assessed reduction ratios (RR) during HD but not HDF employing UV absorbance of spent dialysate (p < 0.05) at 295 nm wavelength with the strongest correlation between the concentration of UA and absorbance. Corresponding removal of IS based on fluorescence at Ex280/Em400 nm during HD and HDF was not affected. Administration of UV-absorbing drugs may in some settings influence the accuracy of optical assessments in spent dialysate of the removal of uremic solutes during haemodialysis treatment of ESKD patients.
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| 2. |
- Paats, Joosep, et al.
(författare)
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Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.
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| 3. |
- Paats, Joosep, et al.
(författare)
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Time-averaged concentration estimation of uraemic toxins with different removal kinetics: a novel approach based on intradialytic spent dialysate measurements
- 2023
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Ingår i: Clinical Kidney Journal. - : OXFORD UNIV PRESS. - 2048-8505 .- 2048-8513. ; 16:4, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- Background Kt/V-urea is the most used marker to estimate dialysis adequacy; however, it does not reflect the removal of many other uraemic toxins, and a new approach is needed. We have assessed the feasibility of estimating intradialytic serum time-averaged concentration (TAC) of various uraemic toxins from their spent dialysate concentrations that can be estimated non-invasively online with optical methods. Methods Serum and spent dialysate levels and total removed solute (TRS) of urea, uric acid (UA), indoxyl sulphate (IS) and beta 2-microglobulin (beta 2M) were evaluated with laboratory methods during 312 haemodialysis sessions in 78 patients with four different dialysis treatment settings. TAC was calculated from serum concentrations and evaluated from TRS and logarithmic mean concentrations of spent dialysate (MlnD). Results Mean (+/- standard deviation) intradialytic serum TAC values of urea, UA, beta 2M and IS were 10.4 +/- 3.8 mmol/L, 191.6 +/- 48.1 mu mol/L, 13.3 +/- 4.3 mg/L and 82.9 +/- 43.3 mu mol/L, respectively. These serum TAC values were similar and highly correlated with those estimated from TRS [10.5 +/- 3.6 mmol/L (R-2 = 0.92), 191.5 +/- 42.8 mu mol/L (R-2 = 0.79), 13.0 +/- 3.2 mg/L (R-2 = 0.59) and 82.7 +/- 40.0 mu mol/L (R-2 = 0.85)] and from MlnD [10.7 +/- 3.7 mmol/L (R-2 = 0.92), 191.6 +/- 43.8 mu mol/L (R-2 = 0.80), 12.9 +/- 3.2 mg/L (R-2 = 0.63) and 82.2 +/- 38.6 mu mol/L (R-2 = 0.84)], respectively. Conclusions Intradialytic serum TAC of different uraemic toxins can be estimated non-invasively from their concentration in spent dialysate. This sets the stage for TAC estimation from online optical monitoring of spent dialysate concentrations of diverse solutes and for further optimization of estimation models for each uraemic toxin.
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| 4. |
- Vanholder, Raymond, et al.
(författare)
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A bench to bedside view of uremic toxins.
- 2008
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Ingår i: Journal of the American Society of Nephrology : JASN. - 1533-3450. ; 19:5, s. 863-70
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Tidskriftsartikel (refereegranskat)abstract
- Reviewing the current picture of uremic toxicity reveals its complexity. Focusing on cardiovascular damage as a model of uremic effects resulting in substantial morbidity and mortality, most molecules with potential to affect the function of a variety of cell types within the vascular system are difficult to remove by dialysis. Examples are the larger middle molecular weight molecules and protein-bound molecules. Recent clinical studies suggest that enhancing the removal of these compounds is beneficial for survival. Future therapeutic options are discussed, including improved removal of toxins and the search for pharmacologic strategies blocking responsible pathophysiologic pathways.
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| 5. |
- Vanholder, Raymond, et al.
(författare)
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The role of EUTox in uremic toxin research.
- 2009
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Ingår i: Seminars in dialysis. - 0894-0959 .- 1525-139X. ; 22:4, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- In this publication, we review the activities of the European Uremic Toxin Work Group (EUTox) in the field of uremic toxin research. Founded in 1999 under the umbrella of the European Society of Artificial Organs (ESAO), and active since 2000, this group focuses essentially on questions related to solute retention and removal during chronic kidney disease, and on the deleterious impact of those solutes on biological/biochemical systems. As of January 1, 2009, the group had met 28 times; it organized the third meeting, "Uremic Toxins in Cardiovascular Disease," which took place in October 2008 in Amiens, France. The current group is composed of 25 members belonging to 23 European research institutions. As of November 1, 2008, in total 69 papers had been published to which at least two different research groups belonging to EUTox have contributed in a collaborative effort. Of these, 40 papers were on original research and eight were specific EUTox reviews or position statements. A website (http://www.eutox.info) summarizes all relevant information concerning the work group. EUTox also developed an interactive uremic toxin database, where concentrations of known toxins are displayed, to be used by researchers in the field. In the future, EUTox intends to continue its focus on bench to bedside research with specific consideration of proteomics, metabonomics, secretomics, and genomics.
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| 6. |
- Vollmer, Tino, et al.
(författare)
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An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the key toxic players within an in-vivo toxic syndrome is crucial to develop targeted therapies. Here, we established a novel method that characterizes the effect of single substances by means of an ex-vivo incubation set-up. We found that primary human spermatozoa elicit a distinct motile response on a (uremic) toxic milieu. Specifically, this approach describes the influence of a bulk toxic environment (uremia) as well as single substances (uremic toxins) by real-time analyzing motile cellular behavior. We established the human spermatozoa-based toxicity testing (HSTT) for detecting single substance-induced toxicity to be used as a screening tool to identify in-vivo toxins. Further, we propose an application of the HSTT as a method of clinical use to evaluate toxin-removing interventions (hemodialysis).
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