Optical Real-Time Cardiorenal Toxin Uric Acid Measurement During Hemodialysis Using a Miniaturized Optical Sensor.

Patients with chronic kidney disease (CKD) are at higher cardiovascular risk than the general population. Cardiovascular diseases, vascular calcification among them, are the leading cause of death in these patients. Factors influencing vascular calcification are oxidative stress, inflammation, and accumulation of uremic toxins during CKD. Uric acid is a cardiorenal toxin that accumulates in the case of kidney malfunction. The primary therapy for replacing kidney function and removing toxins from end-stage renal disease patients is hemodialysis. Effective removal of toxins can be estimated by blood or dialysate lab analysis or optical monitoring. In this study, the authors tested a miniaturized optical sensor for monitoring uric acid levels and removal for the first time in a more extensive clinical study, including Hemodialysis (HD) and Post-dilutional online hemodiafiltration (HDF) procedures with different settings in Tallinn, Estonia. The results (Mean±SD, Lab vs. Sensor) of the uric acid concentration 57.20±34.05 vs. 57.22±33.09 µmol/L, reduction ratio 68.72±10.91 vs. 67.89±12.48 %, and total removed amount 7.00±2.10 vs. 7.33±2.29 mmol did not differ significantly from the values obtained from the clinical laboratory (p<0.05).Clinical Relevance-During this study, a miniaturized optical sensor was tested for the first time in the clinic in different dialysis settings. The results confirm that the sensor is reliable for regularly monitoring cardiorenal toxin uric acid removal during hemodialysis.

Time-averaged concentration estimation of uraemic toxins with different removal kinetics: a novel approach based on intradialytic spent dialysate measurements.

Background: Kt/Vurea 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 ß2-microglobulin (ß2M) 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, ß2M and IS were 10.4 ± 3.8 mmol/L, 191.6 ± 48.1 µmol/L, 13.3 ± 4.3 mg/L and 82.9 ± 43.3 µmol/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 µmol/L (R 2 = 0.79), 13.0 ± 3.2 mg/L (R 2 = 0.59) and 82.7 ± 40.0 µmol/L (R 2 = 0.85)] and from MlnD [10.7 ± 3.7 mmol/L (R 2 = 0.92), 191.6 ± 43.8 µmol/L (R 2 = 0.80), 12.9 ± 3.2 mg/L (R 2 = 0.63) and 82.2 ± 38.6 µmol/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.

Treatment with Paracetamol Can Interfere with the Intradialytic Optical Estimation in Spent Dialysate of Uric Acid but Not of Indoxyl Sulfate.

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.

A Novel Physical Fatigue Assessment Method Utilizing Heart Rate Variability and Pulse Arrival Time towards Personalized Feedback with Wearable Sensors.

This paper proposes a novel method for physical fatigue assessment that can be applied in wearable systems, by utilizing a set of real-time measurable cardiovascular parameters. Daylength measurements, including a morning test set, physical exercise during the day, and an afternoon test set were conducted on 16 healthy subjects (8 female and 8 male). To analyze cardiovascular parameters for physical fatigue assessment, electrocardiography, pulse wave and blood pressure were measured during the test sets. The fatigue assessment questionnaire score, reaction time, countermovement jump height and hand grip strength were also measured and used as reference parameters. This study demonstrates that (i) the compiled test battery can selectively assess the rested vs. physically-fatigued states; (ii) the obtained linear support-vector machine, trained using the heart rate variability based parameter (F-score 0.842, accuracy 0.813) and pulse arrival time based parameter (F-score 0.875, accuracy 0.875) shows a promising ability to classify between the physically mildly fatigued and significantly fatigued states. Despite the somewhat limited study group size, the results of the study are unique and provide a significant advancement on the existing physical fatigue assessment methods towards a personalized and continuous real-time fatigue monitoring system with wearable sensors.

Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin ß2-Microglobulin in Spent Dialysate.

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of ß2-microglobulin (ß2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of ß2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated ß2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of ß2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin ß2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

Data Sharing Under the General Data Protection Regulation: Time to Harmonize Law and Research Ethics?

The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.

Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients.

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.

Removal of Urea, ß2-Microglobulin, and Indoxyl Sulfate Assessed by Absorbance and Fluorescence in the Spent Dialysate During Hemodialysis.

In this study, simultaneous removal assessment of marker molecules from three uremic toxin groups was performed during different hemodialysis treatment modalities using optical characteristics of spent dialysate. Results from optical measurements were compared with the results from chemical laboratory. Ten chronic dialysis patients, mean age 59 ± 15 years, were included in the study during 40 hemodialysis sessions. Low-flux hemodialysis (HD), high-flux hemodialysis (HF), and postdilutional online hemodiafiltration (HDF) with different settings were used. The reduction ratio (RR) and total removed solute (TRS) of three uremic solutes were determined: small molecular weight urea, middle molecular ß2-microglobulin (B2M), and protein-bound indoxyl sulfate (IS). Concentrations of these solutes in the spent dialysate were measured by laboratory (lab) and optical (opt) methods, in the serum by laboratory methods, and calculated RR values in percentage were compared accordingly. Total removed solute was obtained from the total dialysate collection (TDC) using lab and opt methods. The highest RR values were found for urea and B2M, and the lowest for IS. The difference between RR of lab and opt results estimated as mean accuracy (BIAS) was ≤8.1% for all three solutes. Good correspondence between TRS lab vs. opt was achieved, resulting in strong linear correlation values R from 0.727 for urea to 0.971 for IS. Accuracy for TRS values as BIAS ± standard error (SE), comparing lab vs. opt, showed no statistical difference for any of the observed uremic solutes (P > 0.05). The accuracy of the optical method was not influenced by the dialysis modality (HD, HF, and HDF).

Free Pentosidine Assessment Based on Fluorescence Measurements in Spent Dialysate.

The aim of this study was to primarily explore the relationship between free pentosidine and the fluorescence properties of spent dialysate, and also to develop a model to assess the levels of free pentosidine in spent dialysate based on the fluorescence measurements. First, 40 patients (20 females and 20 males) were examined during 40 dialysis sessions. High-pressure liquid chromatography (HPLC) was used to measure the free pentosidine concentrations from the spent dialysate. The full fluorescence spectra of the spent dialysates were recorded and single- and multi-wavelength (MW) models were developed. The average free pentosidine concentrations in the spent dialysate measured by HPLC at the start and end of the dialysis session were (mean ± SD) 4.25 ± 3.11 and 0.94 ± 0.69 µg/L respectively. The removal ratios (RRs) between RR_lab and RR_MW were statistically similar (p > 0.2). The concentration of free pentosidine and the RR can therefore be estimated from the spent dialysate when utilising fluorescence measurements.

4-Pyridoxic Acid in the Spent Dialysate: Contribution to Fluorescence and Optical Monitoring.

AIM: In this work we estimated the contribution of the fluorescence of 4-pyridoxic acid (4-PA) to the total fluorescence of spent dialysate with the aim of evaluating the on-line monitoring of removal of this vitamin B-6 metabolite from the blood of patients with end-stage renal disease (ESRD). METHODS: Spectrofluorometric analysis of spent dialysate, collected from hemodialysis and hemodiafiltration sessions of 10 patients receiving regularly pyridoxine injections after dialysis treatment, was performed in the range of Ex/Em 220-500 nm. 4-PA in dialysate samples was identified and quantified using HPLC with fluorescent and MS/MS detection. RESULTS: Averaged HPLC chromatogram of spent dialysate had many peaks in the wavelength region of Ex320/Em430 nm where 4-PA was the highest peak with contribution of 42.2±17.0% at the beginning and 47.7±18.0% in the end of the dialysis. High correlation (R = 0.88-0.95) between 4-PA concentration and fluorescence intensity of spent dialysate was found in the region of Ex310-330/Em415-500 nm, respectively. CONCLUSION: 4-PA elimination from the blood of ESRD patients can be potentially followed using monitoring of the fluorescence of the spent dialysate during dialysis treatments.

Is Fluorescence Valid to Monitor Removal of Protein Bound Uremic Solutes in Dialysis?

The aim of this study was to evaluate the contribution and removal dynamics of the main fluorophores during dialysis by analyzing the spent dialysate samples to prove the hypothesis whether the fluorescence of spent dialysate can be utilized for monitoring removal of any of the protein bound uremic solute. A high performance liquid chromatography system was used to separate and quantify fluorophoric solutes in the spent dialysate sampled at the start and the end of 99 dialysis sessions, including 57 hemodialysis and 42 hemodiafiltration treatments. Fluorescence was acquired at excitation 280 nm and emission 360 nm. The main fluorophores found in samples were identified as indole derivatives: tryptophan, indoxyl glucuronide, indoxyl sulfate, 5-hydroxy-indoleacetic acid, indoleacetyl glutamine, and indoleacetic acid. The highest contribution (35 ± 11%) was found to arise from indoxyl sulfate. Strong correlation between contribution values at the start and end of dialysis (R2 = 0.90) indicated to the stable contribution during the course of the dialysis. The reduction ratio of indoxyl sulfate was very close to the decrease of the total fluorescence signal of the spent dialysate (49 ± 14% vs 51 ± 13% respectively, P = 0.30, N = 99) and there was strong correlation between these reduction ratio values (R2 = 0.86). On-line fluorescence measurements were carried out to illustrate the technological possibility for real-time dialysis fluorescence monitoring reflecting the removal of the main fluorophores from blood into spent dialysate. In summary, since a predominant part of the fluorescence signal at excitation 280 nm and emission 360 nm in the spent dialysate originates from protein bound derivatives of indoles, metabolites of tryptophan and indole, the fluorescence signal at this wavelength region has high potential to be utilized for monitoring the removal of slowly dialyzed uremic toxin indoxyl sulfate.

Optical Estimation of Beta 2 Microglobulin during Hemodiafiltration ­ Does It Work?

BACKGROUND: Currently, urea reduction seems to be the most widely used dialysis dose parameter. The aim of this study was to investigate the possibility to monitor beta 2-microglobulin (ß2-M) elimination by utilizing the ultraviolet (UV) absorbance of spent dialysate. METHODS: Blood and spent dialysate were collected during two week's sessions in 8 patients, one week in hemodialysis (HD) and one in hemodiafiltration (HDF). Correlation analysis between UV-wavelengths and concentrations of solutes in spent dialysate was performed. The reduction ratio (RR) of concentrations in blood, dialysate and UV-absorbance were compared. RESULTS: Differences between HD and HDF were discovered in wavelength correlation maxima for the solutes. Relative error in RR (%) was larger (p < 0.05) for ß2-M than for the other solutes. The most reasonable explanation is that ß2-M does not absorb UV-radiation; instead, the absorbance of surrogate substances is measured. CONCLUSION: A high correlation between UV-absorbance and ß2-M can be achieved for HDF but not for HD. Still, UV-absorbance could perhaps be used in solely HDF mode for estimation of ß2-M removal.

Lean body mass assessment based on UV absorbance in spent dialysate and dual-energy x-ray absorptiometry.

PURPOSE: The aim of the study was to explore the possibility of assessing lean body mass (LBM) based on UV absorbance measurements in spent dialysate. METHODS: 9 patients on chronic three-times-a-week HD (4 female, 5 male, mean age 58.8 ± 8.6 years) were studied. Blood and spent dialysate samples were collected for 3 consecutive hemodialysis (HD) sessions from every patient. A double-beam spectrophotometer was used for the determination of UV absorbance in the collected spent dialysate samples. Dual-energy x-ray absorptiometry (DXA) scans were performed on an interdialytic day. LBM was calculated based on creatinine concentration in blood (LBMblood) and UV absorbance in spent dialysate (LBMa) and assessed by DXA (LBMDXA). Also, in vitro experiments were carried out to investigate the effect of tissue hydration on DXA measurements. RESULTS: Although LBMa was slightly lower compared to LBMblood, the estimates based on UV absorbance in spent dialysate presented greater accuracy and precision compared to LBMDXA. The significant difference between LBMblood and LBMDXA was with high probability caused by the altered tissue hydration of HD patents. CONCLUSIONS: In summary, the results show that it is possible to asses LBM based on UV absorbance in spent dialysate.

An optical method for serum calcium and phosphorus level assessment during hemodialysis.

Survival among hemodialysis patients is disturbingly low, partly because vascular calcification (VC) and cardiovascular disease are highly prevalent. Elevated serum phosphorus (P) and calcium (Ca) levels play an essential role in the formation of VC events. The purpose of the current study was to reveal optical monitoring possibilities of serum P and Ca values during dialysis. Twenty-eight patients from Tallinn (Estonia) and Linköping (Sweden) were included in the study. The serum levels of Ca and P on the basis of optical information, i.e., absorbance and fluorescence of the spent dialysate (optical method) were assessed. Obtained levels were compared in means and SD. The mean serum level of Ca was 2.54 ± 0.21 and 2.53 ± 0.19 mmol/L; P levels varied between 1.08 ± 0.51 and 1.08 ± 0.48 mmol/L, measured in the laboratory and estimated by the optical method respectively. The levels achieved were not significantly different (p = 0.5). The Bland-Altman 95% limits of agreement between the two methods varied from -0.19 to 0.19 for Ca and from -0.37 to 0.37 in the case of P. In conclusion, optical monitoring of the spent dialysate for assessing the serum levels of Ca and P during dialysis seems to be feasible and could offer valuable and continuous information to medical staff.

Urea Rebound Assessment Based on UV Absorbance in Spent Dialysate.

The aim of the study was to examine the possibility of postdialysis urea rebound assessment using UV-absorbance measurements in spent dialysate. Twenty-six patients on chronic three-times-a-week hemodialysis (HD) were studied in two separate studies. Double-beam spectrophotometer was used for the determination of UV absorbance in the collected spent dialysate samples. Also, on-line UV absorbance was monitored. The equilibrium concentration (C(eq)) of urea at the end of the rebound phase was calculated based on urea concentration in blood and dialysate and UV absorbance in spent dialysate. Based on C(eq), urea rebound was expressed relative to urea concentration at the end of HD (R1) and relative to the decrease in urea concentration during HD (R2). Estimates based on UV-absorbance values in spent dialysate (R(1_a), R(2_a)) slightly over assess postdialysis rebound compared with results based on the blood sample drawn 30 min after HD (R(1_30post), R(2_30post)), but R(1_a) and R(2_a) presented greater consistency and accuracy compared with the estimates based on the intradialytic blood sample (R(1_b), R(2_b)). In summary, the results show that it is possible to assess postdialysis urea rebound in blood based on UV-absorbance measurements in spent dialysate.

Estimation of removed uremic toxin indoxyl sulphate during hemodialysis by using optical data of the spent dialysate.

The aim of this study was to explore the possibility to determine the amount of total removed Indoxyl Sulphate (TR_IS) during dialysis session, an optical method utilizing absorbance and fluorescence spectral data of the spent dialysate was used. Eight uremic patients from Linköping, Sweden and 10 from Tallinn, Estonia, were studied during dialysis treatments. Dialysate samples were taken during each treatment and analyzed at a laboratory. Fluorescence and absorbance spectra of the spent dialysate were measured with spectrofluorophotometer and spectrophotometer. The spectral values were transformed into IS concentration using multiple linear regression model from the total material noted as optical method (Opt). IS concentration was estimated using high-performance liquid chromatography (HPLC) method as a reference. TR_IS values were calculated. Achieved results were compared regarding mean values and SD and collated with the amount of total removed urea value (TR_Urea) for the same dialysis procedures. Mean TR value ± SD (mg) for urea was 28 947 ± 9 241; TR for IS was 151.4 ± 87.3 estimated by HPLC and 149.4 ± 84.9 estimated by Opt. The TR_IS values were not significantly different (p ≤ 0.05). This study indicates, that it is possible to estimate TR_IS using only spectral values of the spent dialysate and the parameter can be used for quantifying the elimination of protein bound uremic toxins during the dialysis procedure.

Accurate dialysis dose evaluation and extrapolation algorithms during online optical dialysis monitoring.

The aim of this study was to propose an improved method for accurate dialysis dose evaluation and extrapolation by means of Kt/ V from online UV-absorbance measurements for real time and continuous treatment monitoring. The study included a total of 24 treatments from ten uremic patients, seven of whom were male and three females. All patients were on chronic thrice-weekly hemodialysis therapy. The study included both stable and unstable treatments. A known signal processing algorithm, Levenberg-Marquardt, and the newly developed SMART were utilized for the removal of disturbances not relevant for dialysis dose evaluation. Finally, the results were compared with the Kt/ V values based on the blood samples. The new data processing algorithm, SMART, removes disturbances, helps estimate the online Kt/ V with significant precision increase and without any time delay, and more effectively predicts the end Kt/ V for the treatment than the known algorithms.

Optical measurement of creatinine in spent dialysate.

AIM: The aim of the study was to develop an optical method for the estimation of creatinine (Cr) removal during dialysis using UV-absorbance. MATERIAL AND METHODS: 29 hemodialysis patients on chronic 3-times-a-week hemodialysis were studied in 6 separate studies. Double-beam pectrophotometer was used for the determination of UV-absorbance in the collected spent dialysate samples. A single wavelength (SW) and a multi-wavelength (MW) model were developed using stepwise regression utilizing Cr values from the laboratory as the dependent parameter. The reduction ratio (RR) and total removed Cr (TRCr) were estimated. RESULTS: For blood-Cr RRb (mean ± SD) was 60.9 ± 5.0% (calibration set) and 58.1 ± 6.0% (validation set), for SW UVabsorbance RR_SW was 61.5 ± 5.9% and 57.3 ± 6.0%, and for MW UV-absorbance RR_MW was 65.8 ± 5.8% and 61.7 ± 6.4% respectively. RR_SW and RRb were not statistically different. RR_MW was higher compared to RRb (p < 0.05). TRCr_lab was 13.8 ± 3.8 mmol, TRCr_SW 14.5 ± 2.5 mmol and TRCr_MW 13.8 ± 2.6 mmol, being not statistically different. CONCLUSION: In summary, creatinine removal during dialysis can be estimated as reduction ratio and total removed creatinine with the UV-absorbance technique.

Paracetamol interference in uric Acid levels in uremic patients revealed by monitoring spent dialysate.

The aim of this study was to assess removal dynamics of paracetamol (PAR), as an extraordinary chromophore in spent dialysate, upon the optical monitoring of dialysis of end-stage renal disease patients with inflammation complications. Seven dialysis sessions of different patients were followed to whom PAR was used as a pain reliever or antipyretic. Spent dialysate was sampled hourly and analyzed using HPLC with MS/MS and UV detection. Quantitative calculations were made on the basis of the peak areas on the chromatograms at 280 nm for uric acid (UA) and 254 nm for PAR and its metabolites (PAR-M). Peaks of UA, PAR, PAR-glucuronide, and PAR-sulphate were identified on the basis of specific mass spectra. Removal of PAR was found to be proportional to that of uric acid if intake of the drug by patient occurred half a day before dialysis. But disturbances of the UV-absorbance curves at 280 nm were observed related to rise of UA concentration in spent dialysate when PAR was taken by patients in the course of dialysis. The mechanism of such relation remains unknown. It was concluded that possible benefits and risks of treatment of uremic patients with paracetamol-containing drugs may need to be reassessed.

Do only small uremic toxins, chromophores, contribute to the online dialysis dose monitoring by UV absorbance?

The aim of this work was to evaluate the contributions of the main chromophores to the total UV absorbance of the spent dialysate and to assess removal dynamics of these solutes during optical on-line dialysis dose monitoring. High performance chromatography was used to separate and quantify UV-absorbing solutes in the spent dialysate sampled at the start and at the end of dialysis sessions. Chromatograms were monitored at 210, 254 and 280 nm routinely and full absorption spectra were registered between 200 and 400 nm. Nearly 95% of UV absorbance originates from solutes with high removal ratio, such as uric acid. The contributions of different solute groups vary at different wavelengths and there are dynamical changes in contributions during the single dialysis session. However, large standard deviation of the average contribution values within a series of sessions indicates remarkable differences between individual treatments. A noteworthy contribution of Paracetamol and its metabolites to the total UV absorbance was determined at all three wavelengths. Contribution of slowly dialyzed uremic solutes, such as indoxyl sulfate, was negligible.