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.

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.

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).

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.

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.

Optical method for cardiovascular risk marker uric acid removal assessment during dialysis.

The aim of this study was to estimate the concentration of uric acid (UA) optically by using the original and processed ultraviolet (UV) absorbance spectra of spent dialysate. Also, the effect of using several wavelengths (multi-wavelength algorithms) for estimation was examined. This paper gives an overview of seven studies carried out in Linköping, Sweden, and Tallinn, Estonia. A total of 60 patients were monitored over their 188 dialysis treatment procedures. Dialysate samples were taken and analysed by means of UA concentration in a chemical laboratory and with a double-beam spectrophotometer. The measured UV absorbance spectra were processed. Three models for the original and three for the first derivate of UV absorbance were created; concentrations of UA from the different methods were finally compared in terms of mean values and SD. The mean concentration (micromol/L) of UA was 49.7 ± 23.0 measured in the chemical laboratory, and 48.9 ± 22.4 calculated with the best estimate among all models. The concentrations were not significantly different (P ≥ 0.17). It was found that using a multi-wavelength and processed signal approach leads to more accurate results, and therefore these approaches should be used in future.

Concentration of uric acid removed during dialysis. Estimated by multi wavelength and processed ultra violet absorbance spectra.

The aim of this study was to estimate the concentration of uric acid (UA) optically by using original and processed ultra violet (UV) absorbance spectra's of the spent dialysate. Also the effect of using several wavelengths for estimation was examined.

HPLC study of uremic fluids related to optical dialysis adequacy monitoring.

PURPOSE: The aim of this study was to investigate uremia-related high-performance liquid chromatography (HPLC) ultraviolet (UV) absorbance profiles of serum and spent dialysate and to study the removal of uremic retention solutes in connection with optical dialysis adequacy monitoring. METHODS: 10 uremic patients were investigated using online spectrophotometry at a wavelength of 280 nm over the course of 30 hemodialysis treatments. The dialysate and blood samples were taken and analyzed simultaneously using standard biochemical methods and reversed-phase HPLC. Filters with cutoff at 3 kDa and 70 kDa were used for the pre-treatment of the serum. The chromatographic peaks were detected by a UV detector at wavelengths of 254 and 280 nm. RESULTS: This study indicated that the main solute responsible for UV absorbance in the spent dialysate is a low-molecular-weight, water-soluble, non-protein-bound compound uric acid (UA). Three additional uremic retention solutes - creatinine (CR), indoxyl sulphate (IS) and hippuric acid (HA) - were identified from the HPLC profiles. The number of detected HPLC peaks was not significantly different for a serum filtered through the 3 kDa or 70 kDa cutoff filters, and was lower for the spent dialysate, indicating that the molecular weight (MW) of the main UV chromophores in the uremic fluids did not exceed 3 kDa. The reduction ratio (RR) estimated by the total area of HPLC peaks at 254 nm and 280 nm in the serum and by the online UV absorbance at 280 nm was best related to the removal of small water-soluble non-protein bound solutes like urea (UR), CR and UA. CONCLUSIONS: The present study contributes new information on the removal of uremic retention solutes during hemodialysis and on the origin of the optical dialysis adequacy monitoring signal.

Optical online monitoring of uric acid removal during dialysis.

This study estimates the total removal of uric acid (TR(UA)) by online UV absorbance measurements in the spent dialysate in two different dialysis centers in Estonia and Sweden. Sixteen dialysis patients were included. All dialysate was collected that gave the reference for TR(UA). Two regression models were investigated: one for each patient (UV1) and one for the entire material (UV2). TR(UA) from the three methods was in the same order but showed a statistically significant difference when the UV2 model was built on data from both centers together. TR(UA), (n = 56) was (mean +/- SD, micromol): 5,854 +/- 1,377 for reference, 6,117 +/- 1,795 for UV1 and 5,762 +/- 1,591 for UV2. Six patients were monitored 1 year after the first study session, using the same models as the previous year, still having a nonsignificant difference. The results show the possibility of estimating TR(UA) by using UV absorbance. The method appeared to be reliable also in long-term patient monitoring.

A multicentre study of an enhanced optical method for measuring concentration of uric acid removed during dialysis.

The aim of this study was to compare concentration measurements of uric acid (UA) removed during dialysis by two algorithms based on UV-absorbance and the 1st derivate of UV absorbance. Ten uremic patients from Tallinn and ten from Linköping, during 30+40 haemodialysis treatments, were followed at the Departments of Dialysis and Nephrology at North-Estonian Medical Centre and at Linköping University Hospital. The dialysate samples were taken and analyzed by means of UA concentration at the chemical laboratory and with a double-beam spectrophotometer. UV absorbance and derivate of UV absorbance was transformed into UA concentration in the spent dialysate using the regression models from the calibration set of material, noted as UV-absorbance (UV_A) and the 1st derivate of UV absorbance (UV_D) method. These models were tested on validation set of material and concentrations of UA from the two methods were compared regarding mean values and SD. Mean concentration of UA were 52.7 +/- 25.0 micromol/l measured at the chemical laboratory (UA_Lab), 54.9 +/- 23.8 micromol/l determined by UV_A and 52.9 +/- 23.0 micromol/l determined by UV_D. The results of mean concentrations were not significantly different (p > or = 0.54). The systematic errors were -7.8 % and -3.3% and random errors were 15.8 % and 10.4 % using UV_A and UV_D respectively. The systematic and random errors were significantly different (p < 0.05) indicating that the new algorithm enables more accurate UA estimation.

Optical dialysis adequacy sensor: wavelength dependence of the ultra violet absorbance in the spent dialysate to the removed solutes.

A need for dialysate-based, on-line, continuous monitoring systems for the control of dialysis efficiency and the prevention of dialysis-associated complications is arisen due to increasing number of dialysis patients and related treatment quality requirements. The aim of this study was to investigate the wavelength dependence between the the ultra-violet (UV) absorbance in the spent dialysate and the retained solutes removed during the hemodialysis in order to explain possibilities to estimate removal of the solutes by the optical dialysis adequacy sensor. Ten uremic patients, during 30 hemodialysis treatments, were followed at the Department of Dialysis and Nephrology, North-Estonian Regional Hospital. The dialysate samples were taken and analyzed with spectrophotometer to get absorbance spectra. The results confirm previous studies considering similarity for the UV-spectrum on the spent dialysate samples during a single dialysis session indicating presence of the same type of chromophores in the spent dialysate removed from the patient's blood for different patients groups. At the same time the highest correlation in the spent dialysate for urea, creatinine, potassium, and phosphate was obtained at the wavelength 237 nm that is a new finding compared to earlier results. The highest correlation between the UV-absorbance and uric acid in the spent dialysate was obtained at the wavelength 294 nm. Presence of at least two different wavelength ranges may add selectivity for monitoring several compounds. Our study indicates that the technique has a potential to estimate the removal of retained substances.

Optical dialysis adequacy sensor: contribution of chromophores to the ultra violet absorbance in the spent dialysate.

Several on-line methods have been developed to standardize the assessment of dialysis adequacy. Earlier studies have demonstrated that on-line monitoring of total ultra violet (UV) absorbance in spent dialysate can be utilized to follow continuously a single hemodialysis session. The aim of this study was to investigate the contribution of different compounds, acting as chromophores, to the UV-absorbance in the spent dialysate in order to explain origin of the cumulative and integrated UV-absorbance measured by the optical dialysis adequacy sensor. Four uremic patients, during 12 hemodialysis treatments, were followed by the optical dialysis adequacy sensor using the wavelength of 280 mn. The dialysate samples were taken and analyzed using reversed phase high performance liquid chromatography (HPLC). The total number of detected peaks from the HPLC gradient separation profiles measured at the wavelength 280 nm for the samples collected 10 mm after the start of hemodialysis (Mean +/- SD) was 38 +/- 6. The relative contribution from the area of 10 main peaks to the total area of all detected peaks in percentage was 91.01 +/- 2.52 %. The optical dialysis adequacy sensor provides continuous, on-line hemodialysis measurements and may immediately identify and alert to any deviations in the dialysis. Our study indicates that there exists a number of prevalent compounds that are the main cause of the cumulative and integrated UV- absorbance.