Ivo Fridolin

On-line monitoring of solutes in dialysate using absorption of ultraviolet radiation: technique description.

Purpose The aim of this work was to describe a new optical method for monitoring solutes in a spent dialysate using absorption of UV radiation. Method The method utilises UV-absorbance determined in the spent dialysate using a spectrophotometrical set-up. Measurements were performed both on collected dialysate samples and on-line. During on-line monitoring, a spectrophotometer was connected to the fluid outlet of the dialysis machine, with all spent dialysate passing through a specially-designed cuvette for optical single-wavelength measurements. The concentrations of several substances of various molecular sizes, electrical charge, transport mechanism, etc. were determined in the dialysate and in the blood using standard laboratory techniques. The correlation coefficient between UV-absorbance of the spent dialysate and concentration of the substances in the spent dialysate and in the blood was calculated from data based on the collected samples. Results The obtained on-line UV-absorbance curve demonstrates the possibility to follow a single hemodialysis session continuously and to monitor deviations in the dialysator performance using UV-absorbance. The experimental results indicate a very good correlation between UV-absorbance and several small waste solutes removed such as urea, creatinine and uric acid in the spent dialysate and in the blood for every individual treatment at a fixed wavelength of 285 nm. Moreover, a good correlation between the UV-absorbance and substances like potassium, phosphate and β2-microglobulin was obtained. The lowest correlation was achieved for sodium, calcium, glucose, vitamin B12 and albumin. Conclusions A technique for on-line monitoring of solutes in the spent dialysate utilising the UV-absorbance was developed. On-line monitoring during a single hemodialysis session exploiting UV-absorbance represents a possibility to follow a single hemodialysis session continuously and monitor deviations in dialysis efficiency (e.g. changes in blood flow and clearance). The UV-absorbance correlates well to the concentration of several solutes known to accumulate in dialysis patients indicating that the technique can be used to estimate the removal of retained substances.

Estimation of delivered dialysis dose by on-line monitoring of the ultraviolet absorbance in the spent dialysate

BACKGROUND Several methods are available to determine Kt/V, from predialysis and postdialysis blood samples to using on-line dialysate urea monitors or to ionic dialysance using a conductivity method. The aim of this study is to compare Kt/V calculated from the slope of the logarithmic on-line ultraviolet (UV) absorbance measurements, blood urea Kt/V, dialysate urea Kt/V, and Kt/V from the Urea Monitor 1000 (UM; Baxter Healthcare Corp, Deerfield, IL). METHODS Thirteen uremic patients on chronic thrice-weekly hemodialysis therapy were included in the study. The method uses absorption of UV radiation by means of a spectrophotometric set-up. Measurements were performed on-line with the spectrophotometer connected to the fluid outlet of the dialysis machine; all spent dialysate passed through a specially designed cuvette for optical single-wavelength measurements. UV absorbance measurements were compared with those calculated using blood urea and dialysate urea, and, in a subset of treatments, the UM. RESULTS Equilibrated Kt/V (eKt/V) obtained with UV absorbance (eKt/Va) was 1.19 +/- 0.23; blood urea (eKt/Vb), 1.30 +/- 0.20, and dialysate urea (eKt/Vd), 1.26 +/- 0.21, and Kt/V in a subset measured by the UM (UM Kt/V) was 1.24 +/- 0.18. The difference between eKt/Vb and eKt/Va was 0.10 +/- 0.11, showing a variation similar to the difference between eKt/Vb and eKt/Vd (0.03 +/- 0.10) and in a subset between eKt/Vb and UM Kt/V (-0.02 +/- 0.11). CONCLUSION The study suggests that urea Kt/V can be estimated by on-line measurement of UV absorption in the spent dialysate.

On-line monitoring of solutes in dialysate using wavelength-dependent absorption of ultraviolet radiation

The aim of the study was to assess the wavelength dependence of the UV absorbance during monitoring of different compounds in the dialysate. UV absorbance was determined by using a double-beam spectrophotometer on dialysate samples taken at pre-determined times during dialysis, over a wavelength range of 180–380 nm. Concentrations of several removed substances, such as urea, creatinine, uric acid, phosphate andβ2-microglobulin, were determined in the blood and in the spent dialysate samples using standard laboratory techniques. Millimolar extinction coefficients, for urea, creatinine, monosodium phosphate and uric acid were determined during laboratory bench experiments. The correlation between UV absorbance and substances both in the dialysate and in the blood was calculated at all wavelengths. A time-dependent UV absorbance was determined on the collected dialysate samples from a single dialysis session over a wavelength range of 200–330 nm. The highest contribution from observed compounds relative to the mean value of the absorbance was found around 300 nm and was approximately 70%. The main contribution to the total absorbance from uric acid was confirmed at this wavelength. The highest correlation for uric acid, creatinine and urea was obtained at wavelengths from 280 nm to 320 nm, both in the spent dialysate and in the blood. The wavelength region with the highest correlation for phosphate andβ2-microglobulin, with a suitable UV-absorbance dynamic range, was from 300 to 330 nm. In the wavelength range of 220–270 nm the highest absorbance sensitivity for the observed substances was obtained. A suitable wavelength range for instrumental design seems tobe around 290–330 nm. The relatively high correlation between UV absorbance and the substances in the spent dialysate and in the blood indicates that the UV-absorbance technique can estimate the removal of several retained solutes known to accumulate in dialysis patients.

Optical non-invasive technique for vessel imaging: I. Experimental results

This paper investigates some prerequisites for vessel imaging based on diffuse reflectance measurements in order to develop an optical non-invasive method for the imaging and monitoring of vessels. The method utilizes near-infrared (NIR) radiation (890 nm) from a light emitting diode. The light is guided into the tissue via an optical fibre (diameter 1.0 mm). The backscattered light is collected by an optical fibre of the same type and detected by an optical power meter. The fibres are moved over the skin in two directions with the aid of two motors operated by a microcomputer. Spatially resolved reflectance at the skin surface could be presented as a vessel-map in a colour-coded form on a computer screen. Experimental results indicate that the vessel imaging facility depends upon source-detector separation, relative position and vessel depth, and does not depend essentially on the radiant power from the light source. It is shown that, by a proper choice of probe parameters, one can improve the vessel identification ability. After vessel imaging the technique can potentially be used to monitor several physiological parameters on a selected vascular bed or to distinguish between injured and healthy tissue by monitoring local blood flow, oxygen saturation and the recirculation, pre- and post-operatively.

Optical non-invasive technique for vessel imaging:II. A simplified photon diffusion analysis

The purpose of this paper is to explain theoretically the origin of previously presented experimental results by an optical non-invasive method using NIR for imaging blood vessels based on a specific combination of several physical parameters. The theoretical model is based on the diffusion approximation derived from the transport theory deep in a bulk tissue. An analytical solution was obtained describing photon behaviour under certain conditions during vessel identification. The modelled results indicate that the vessel identification facility depends upon source-detector separation and vessel depth, and does not depend essentially on the radiant power from the light source. The solution offers a relatively simple theoretical explanation of the experimental results and can be applied to several other clinical applications using similar technical solutions.

Optical Online Monitoring of Uric Acid Removal during Dialysis

This study estimates the total removal of uric acid (TRUA) 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 TRUA. Two regression models were investigated: one for each patient (UV1) and one for the entire material (UV2). TRUA 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. TRUA, (n = 56) was (mean ± SD, µmol): 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 TRUA by using UV absorbance. The method appeared to be reliable also in long-term patient monitoring.

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.

Dialysis dose and nutrition assessment by optical on-line dialysis adequacy monitor.

AIM In light of the variability of dialysis sessions, on-line monitoring could improve hemodialysis (HD) adequacy. A new optical Dialysis Adequacy Monitor (DIAMON) prototype enables to estimate dialysis dose and protein nitrogen appearance (PNA) at every dialysis session. The aim of this study was to compare the adequacy of dialysis treatment and the patients nutritional status by pre-and post-dialysis blood samples, the DIAMON prototype and Total Dialysate Collection (TDC). MATERIAL AND METHODS Ten patients were monitored during three consecutive hemodialysis sessions during one week. Blood samples were drawn before the start of dialysis and at the end of dialysis. The DIAMON prototype was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through during the on-line experiments, and TDC was performed for all dialysis treatments. Equilibrated Kt/V (eKt/V) values were estimated from blood-urea (eKt/Vb) and from DIAMON (eKt/Va), and normalized PNA (nPNA) values from TDC and DIAMON, respectively. The variable volume single pool urea kinetic modeling (VVSP UKM) was also utilized for single-pool Kt/V (spKt/V) and nPNA estimation. RESULTS The mean +/- SD given by eKt/Vb was 1.08 +/- 0.22 (n = 30), and eKt/Va 1.05 +/- 0.21 (n = 28). The mean +/- SD of nPNA was 0.73 +/- 0.15 g/kg/day (n = 29) from TDC, and 0.73 +/- 0.14 g/kg/day (n = 28) using DIAMON prototype. The mean values of eKt/V from blood samples and nPNA from TDC were not statistically different from the corresponding values estimated by DIAMON (p < 0.05). Generally the delivered dialysis dose and dietary protein intake of the patients observed during the study using the DIAMON prototype was very similar to that obtained by TDC and VVSP UKM. CONCLUSION The optical dialysis adequacy sensor, DIAMON, provides continuous, on-line measurements of dialysis adequacy and permits longitudinal analysis of the delivered dialysis dose and patients nutritional status, and can immediately identify, and alert to, any deviations in dialysis treatment.

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.

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.