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  • 1.
    Andersson, Roger
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Fridolin, Ivo
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Magnusson, M.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Measurements of solutes in dialysate using UV-absorption: analysis of the factors influencing correlation between UV-absorption and solutes in the spent dialysate2002Other (Other (popular science, discussion, etc.))
  • 2.
    Andersson, Roger
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Fridolin, Ivo
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Magnusson, Martin
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Ask, Per
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Analysis of the relationship between UV-absorbance of solute contents during a dialysis sessionManuscript (preprint) (Other academic)
    Abstract [en]

    In this paper, the influence from patient anamnesis and haemodialysis session specifications onto the relationship between obtained ultra violet (UV) absorbance and urea concentration in the spent dialysate were discussed. A characterisation of the relationship was done by an intercept value and a slope. Recently, a new a dialysate monitoring device, using UV- absorbance, been developed by our group which has found a relationship between the UV- absorbance and waste products in the dialysate but this relationship vary between patients. In the present investigation, 13 patients performing totally 84 sessions were characterised using 31 possible affecting parameters. Using a multi-regression analysis 11 parameters were found significant as affecting parameters. In a novel mathematical model approach the obtained UV- absorbance and incorporating possible affecting parameters we could predict urea concentration from the UV-absorption in the spent dialysate in the total material of patients and dialysis sessions. For all the 84 sessions R2 between 0.938 and 0.996 were obtained. A performed analysis of variance rejects the assumption of equal conditions for the relationship between diabetics and non-diabetics patients in the material (F=5.2 for intercept and F=14.4 for slope). The urea concentration could be estimated with an accuracy of 11% (one standard deviation) which is normally clinically sufficient. The non-invasive UV -absorption method therefore seems to have great potential for monitoring and control haemodialysis sessions.

  • 3.
    Arund, Jürgen
    et al.
    Tallinn University of Technology, Estonia.
    Tanner, Risto
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Do Only Small Uremic Toxins, Chromophores, Contribute to the Online Dialysis Dose Monitoring by UV Absorbance?2012In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 4, no 10, p. 849-861Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Fridolin, Ivo
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Photon propagation in tissue and in biological fluids: applied for vascular imaging and haemodialysis monitoring2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on the photon propagation in tissue and in biological fluids in two main areas: (1) optical vessel imaging and (2) monitoring solutes removed in haemodialysis.

    The aim of the optical vessel imaging study was to design and assess a new optical scanning technique for vessel imaging using NIR radiation. The results indicated that veins could be determined at three vascular levels (superficial, intermediate and deep) down to 3 mm. Moreover, experimental results demonstrated 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. After vessel imaging the technique can potentially be used to monitor several physiological parameters on a selected vascular bed (e.g. local blood flow, oxygen saturation).

    The theoretical model, based on the diffusion approximation, was developed to explain theoretically the origin of experimental results. An analytical solution was obtained describing photon propagation under certain conditions during vessel identification. The modelled results confirmed previously obtained experimental results.

    A new optical method for monitoring solutes in a spent dialysate using absorption of UV-radiation was developed. The obtained on-line UV-absorbance curve demonstrates the possibility to follow a single haemodialysis session continuously and to monitor deviations in the dialysator performance using UV-absorbance. The experimental results indicated that 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.

    Furthermore, a clinical study suggested that the delivered dialysis dose in terms of the traditional urea Kt/V could be estimated by on-line measurement of the UV-absorption in the spent dialysate. This means that the UV-method may add a new methodology for improvement of the quality and adequacy of the dialysis.

    An investigation of the wavelength dependence of the UV-absorbance when monitoring different compounds in the dialysate showed that the UV-absorbance correlates well to several small molecular weight solutes ( < 200 D), around 290-310 nm. The highest contribution to the total absorbance from the observed compounds was confirmed in this wavelength region. The results indicated, that it might be possible to measure the elimination of several substances that are retained in the uraemic patients and with potential clinical significance. From thisviewpoint, the UV-absorbance monitoring technique may become a more universal method to ensure the quality and adequacy of the dialysis.

    List of papers
    1. Optical non-invasive technique for vessel imaging: I. Experimental results
    Open this publication in new window or tab >>Optical non-invasive technique for vessel imaging: I. Experimental results
    2000 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 12, p. 3765-3778Article in journal (Refereed) Published
    Abstract [en]

    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.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-54930 (URN)10.1088/0031-9155/45/12/318 (DOI)
    Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2017-12-12
    2. Optical non-invasive technique for vessel imaging: II. A simplified photon diffusion analysis
    Open this publication in new window or tab >>Optical non-invasive technique for vessel imaging: II. A simplified photon diffusion analysis
    2000 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 12, p. 3779-3792Article in journal (Refereed) Published
    Abstract [en]

    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.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-32636 (URN)10.1088/0031-9155/45/12/319 (DOI)18553 (Local ID)18553 (Archive number)18553 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
    3. On-line monitoring of solutes in dialysate using adsorption of ultraviolet radiation: technical description
    Open this publication in new window or tab >>On-line monitoring of solutes in dialysate using adsorption of ultraviolet radiation: technical description
    2002 (English)In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 25, no 8, p. 748-761Article in journal (Refereed) Published
    Abstract [en]

    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 beta2-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.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-54937 (URN)12296459 (PubMedID)
    Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2017-12-12
    4. Estimation of delivered dialysis dose by on-line monitoring of the ultraviolet absorbance in the spent dialysate
    Open this publication in new window or tab >>Estimation of delivered dialysis dose by on-line monitoring of the ultraviolet absorbance in the spent dialysate
    2003 (English)In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 41, no 5, p. 1026-1036Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keywords
    Hemodialysis (HD), dialysis monitoring, dialysis dose, spectrophotometry, absorption, ultraviolet (UV), solute removal, spent dialysate, dialysis adequacy, dialysis efficiency, urea, Kt/V
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14191 (URN)10.1016/S0272-6386(03)00200-2 (DOI)
    Available from: 2007-01-04 Created: 2007-01-04 Last updated: 2017-12-13
    5. On-line monitoring of solutes in dialysate using wavelength-dependent absorption of ultraviolet radiation
    Open this publication in new window or tab >>On-line monitoring of solutes in dialysate using wavelength-dependent absorption of ultraviolet radiation
    2003 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 41, no 3, p. 263-270Article in journal (Refereed) Published
    Abstract [en]

    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 and β 2-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 and β 2-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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24476 (URN)10.1007/BF02348430 (DOI)6592 (Local ID)6592 (Archive number)6592 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
  • 5.
    Fridolin, Ivo
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Hansson, Kurt
    Linköping University, Department of Mathematics. Linköping University, The Institute of Technology.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Optical non-invasive technique for vessel imaging: II. A simplified photon diffusion analysis2000In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 12, p. 3779-3792Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Fridolin, Ivo
    et al.
    Tallinn University, Estonia.
    Holmar, Jana
    Tallinn University, Estonia.
    Arund, Jürgen
    Tallinn University, Estonia.
    Tanner, Risto
    Tallinn University, Estonia.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Optical dialysis dose estimation for B2-microglubulin by fluorescencein the spent dialysate2011Conference paper (Refereed)
  • 7.
    Fridolin, Ivo
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    On-line monitoring of solutes in dialysate using wavelength-dependent absorption of ultraviolet radiation2003In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 41, no 3, p. 263-270Article in journal (Refereed)
    Abstract [en]

    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 and β 2-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 and β 2-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.

  • 8.
    Fridolin, Ivo
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Optical non-invasive technique for vessel imaging: I. Experimental results2000In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 45, no 12, p. 3765-3778Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Fridolin, Ivo
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Lindberg, Lars-Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Scanner for vessel identification and monitoring (SVIM)1998In: BIOs Conference,1998, 1998Conference paper (Other academic)
  • 10.
    Fridolin, Ivo
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Magnusson, M.
    Lindberg, Lars-Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Measurement of solutes in dialysate using UV absorption2001In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 4263, p. 40-47Conference paper (Other academic)
    Abstract [en]

    The aim of this work was to describe a new method for optical monitoring of solutes in a spent dialysate. The method utilizes UV light absorption employing a commercially available spectrophotometer. Measurements were performed both on collected dialysate samples and on-line. The concentration of several removed solutes and electrolytes in the serum and in the dialysate was determined simultaneously using standard laboratory techniques. During on-line monitoring the spectrophotometer was connected to the fluid outlet of the dialysis machine. On-line measurements during a single hemodialysis session demonstrated a possibility to monitor deviations in the dialysator performance (e.g. dialysator in bypass). The experimental results indicated a good correlation between UV absorption and several removed solutes (urea, creatinine) in the spent dialysate. The correlation coefficient for urea and creatinine concentrations in the dialysate was very high for every individual treatment. The UV absorbance correlates well to the concentrations of several solutes thought to be uremic toxins. The results indicate that the technique can be used as a continuous, on-line method for monitoring deviations in the dialysator performance and may estimate the removal of the overall toxins. In the future, the new method will be used to evaluate parameters describing delivery of the prescribed treatment dose such as KT/V and Urea Reduction Rate (URR).

  • 11.
    Fridolin, Ivo
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Magnusson, Martin
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    On-line monitoring of solutes in dialysate using adsorption of ultraviolet radiation: technical description2002In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 25, no 8, p. 748-761Article in journal (Refereed)
    Abstract [en]

    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 beta2-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.

  • 12.
    Holmar, Jana
    et al.
    Tallinn University of Technology, Estonia.
    Arund, Jürgen
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Tanner, Risto
    Tallinn University of Technology, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    New optical method for estimation of protein bound uremic toxins elimination2012Conference paper (Refereed)
    Abstract [en]

    The aim of this study was to investigate the possibility to determine the amount of removed Indoxyl Sulphate (IS) during dialysis session. An optical method using fluorescence spectra was used.

    Eight uremic patients were studied during three dialysis treatments per patient in one week at the Department of Nephrology at Linköping University Hospital. Dialysate samples were taken during each treatment and analyzed at laboratory. IS concentration was estimated using HPLC method, and fluorescence spectra was measured with spectrofluorophotometer. The fluorescence spectral values were transformed into IS concentration using regression model from the total material noted as fluorescence method (F). Removal ratio (RR) was calculated for both. Achieved results were compared regarding mean values and SD and collated with urea reduction ratio (URR) of same dialysis procedures.

    Mean RR value (%) for urea was 74.55±8.11. RR for IS estimated by HPLC was 54.01±8.44 % and by F 58.95±10.94 %. The values were not significantly different (p≤0.05).

    This study indicates, that it is possible to estimate RR of IS using only fluorescence values of the spent dialysate and achieved parameter can be used for describing the elimination of protein bound uremic toxins during the dialysis procedure.

  • 13.
    Holmar, Jana
    et al.
    Tallinn University of Technology, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Luman, Merike
    Estonian Medical Centre, Tallinn, Estonia.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Serum uric acid level and long term survival in dialysis patients2013In: 50th ERA-EDTA Congress, Istanbul, 2013, 2013Conference paper (Other academic)
  • 14.
    Holmar, Jana
    et al.
    Tallinn University of Technology, Estonia .
    Uhlin, Fredrik
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Ferenets, R
    Tallinn University of Technology, Estonia.
    Lauri, K
    Tallinn University of Technology, Estonia.
    Tanner, R
    Tallinn University of Technology; Estonia.
    Arund, J
    Tallinn University of Technology, Estonia.
    Luman, M
    Tallinn University of Technology, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Estimation of removed uremic toxin indoxyl sulphate during hemodialysis by using optical data of the spent dialysate2013In: IEEE Engineering in Medicine and Biology Society Conference Proceedings, IEEE , 2013, p. 6707-6710Conference paper (Refereed)
    Abstract [en]

    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.

  • 15.
    Lindberg, Lars-Göran
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Fridolin, Ivo
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Magnusson, M
    Non-invasive optical dialysate monitoring1999In: Congress of the European Renal Association, European Dialysis and Transplant Association,1999, 1999Conference paper (Refereed)
  • 16.
    Tomson, R
    et al.
    Tallinn University of Technology, Estonia .
    Fridolin, Ivo
    Tallinn University of Technology, Estonia .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Holmar, Jana
    Tallinn University of Technology, Estonia .
    Lauri, K.
    Tallinn University of Technology, Estonia .
    Luman, M.
    Estonian Medical Centre, Tallinn, Estonia.
    Development of the model for the optical monitoring of urea in spent dialysate2012In: Electronics Conference (BEC), 2012, 2012, p. 179-182Conference paper (Refereed)
    Abstract [en]

    The aim of the study was to develop a mathematical model suitable for the estimation of urea concentration removed during dialysis through UV-absorbance. 29 haemodialysis patients on chronic three-times-a-week haemodialysis were studied in 6 separate studies. Double-beam spectrophotometer 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 urea values from the laboratory as the dependent parameter. For SW model R2 was 0.656 (calibration set) and 0.729 (validation set), for MW model R2 was 0.696 and 0.764, respectively. In summary, the urea concentration removed during dialysis can be estimated with UV-absorbance technique.

  • 17.
    Tomson, Ruth
    et al.
    Tallinn University of Technology, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Holmar, Jana
    Tallinn University of Technology, Estonia.
    Lauri, Kai
    Tallinn University of Technology, Estonia.
    Luman, Merike
    North Estonia Medical Center, Tallinn, Estonia.
    Optical measurement of creatinine in spent dialysate2013In: Clinical Nephrology, ISSN 0301-0430, Vol. 79, no 2, p. 107-117Article in journal (Refereed)
    Abstract [en]

    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.

  • 18.
    Tomson, Ruth
    et al.
    Tallinn University of Technology, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Holmar, Jana
    Tallinn University of Technology, Estonia.
    Lauri, Kai
    Tallinn University of Technology, Estonia.
    Luman, Merike
    North Estonia Medical Centre, Tallinn, Estonia.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Development of a method for optical monitoring of creatinine in the spent dialysate2011In: Estonian Journal of Engineering, ISSN 1736-6038, Vol. 17, no 2, p. 140-150Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to develop a method suitable for the estimation of the amount of creatinine, removed during dialysis through UV-absorbance. Sixteen uremic patients, seven females and nine males, on chronic thrice-weekly hemodialysis were included in the study. Double-beam spectrophotometer was used for the determination of UV-absorbance in the collected spent dialysate samples. Due to differences in independent variables, two multi-wavelength models (m1 and m2) were developed using stepwise regression, utilizing creatinine values from the laboratory as the dependent parameter. The coefficient of determination, R2 was 0.8690 for the first and 0.9103 for the second model. The systematic error, estimated as BIAS, was zero for both models compared to the creatinine values from the laboratory. The standard errors were 10.06 µmol/l and 15.24 µmol/l for m1 and m2, respectively. The average reduction ratio (RR) from creatinine blood values was 59.8 ± 5.4% (N = 50), average RR from m1 was 63.7 ± 7.3% (N = 50) and average RR from m2 was 64.8 ± 6.4% (N = 48). In summary, the amount of creatinine removed as well as the reduction ratio of creatinine during dialysis can be estimated with UV-absorbance technique.

  • 19.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia.
    Optical monitoring of dialysis dose2013In: Modeling and control of dialysis systems: Volume 2: Biofeedback systems and soft computing techniques of dialysis / [ed] Ahmad Taher Azar, Springer Berlin/Heidelberg, 2013, p. 867-928Chapter in book (Other academic)
    Abstract [en]

    Utilizing optics in hemodialysis estimating quality parameters for dialysis dose has been developed during the last ten years. In principle, two optical techniques have made progress toward clinical use, namely the ultraviolet (UV) absorbance- and the near infrared (NIR) techniques. Both methods have shown reliable results of estimating urea in the spent dialysate resulting in the possibility to calculate urea-based quality parameters of dialysis dose in terms of Kt/V and URR. Even nutrition parameters derived from optical urea estimations has been provided to be possible using the UV absorbance method. The UV absorbance method cannot measure urea as a single solute; instead the high correlation between urea concentration and UV absorbance in spent dialysate is utilized when estimating urea parameters. The NIR-method can measure urea directly using signal processing of the raw NIR spectra. Predicted urea concentrations from the NIR measurement show an excellent agreement to urea concentrations measured by the standard chemical assays. The UV-method has recently been commercialized as a monitoring tool for dialysis dose in terms of the urea-based parameters, Kt/V and URR. On-going research is now focusing to monitor even other waste solutes than urea in spent dialysate. This aims to move towards a more comprehensive picture of the dialysis clearance process that is strongly linked to morbidity and survival of the dialysis patients compared with current dialysis dose calculations.

  • 20.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Fridolin, Ivo
    Centre of Biomedical Engineering, Tallinn Technical University, Tallinn, Estonia.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Magnusson, Martin
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Estimating total urea removal and protein catabolic rate by monitoring UV absorbance in spent dialysate2005In: Nephrology Dialysis Transplantation, ISSN 0931-0509, Vol. 20, no 11, p. 2458-2464Article in journal (Refereed)
    Abstract [en]

    Background. Dialysate-based, on-line measurements of Kt/V and protein catabolic rate (PCR) in dialysis patients have been considered more accurate compared with measurements on the blood side during dialysis. The primary aim of this study was to compare total removed urea (TRU) and PCR, normalized to body weight (nPCRw), obtained by three dialysate-based methods: (i) on-line ultraviolet (UV) absorbance of the spent dialysate; (ii) total dialysate collection (TDC), as reference method; and (iii) Urea Monitor 1000 (UM) from Baxter Healthcare Corp.

    Methods. We studied 10 uraemic patients on chronic, thrice-weekly haemodialysis. We made absorption measurements (UV radiation) on-line with a spectrophotometer connected to the fluid outlet of the dialysis machine, with all spent dialysate passing through an optical cuvette for single-wavelength measurements. UV absorbance measurements were compared with TDC and the UM.

    Results. nPCRw obtained with UV absorbance was 0.82±0.17, that from TDC 0.81±0.18, and that measured by UM 0.87±0.18, which was significantly higher than the results of the other methods. The difference between nPCRw calculated by TDC and by UM was –0.05±0.06, showing a slightly lower SD than the difference between nPCRw by TDC and UV absorbance, –0.01±0.07.

    Conclusion. The study demonstrates that TRU, and consequently PCR, can be estimated by on-line measurement of the UV absorption in the spent dialysate.

  • 21.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Fridolin, Ivo
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Magnusson, Martin
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Estimation of delivered dialysis dose by on-line monitoring of the ultraviolet absorbance in the spent dialysate2003In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 41, no 5, p. 1026-1036Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Fridolin, Ivo
    Centre of Biomedical Engineering, Tallinn Technical University, Tallinn, Estonia.
    Magnusson, Martin
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Dialysis dose (Kt/V) and clearance variation sensitivity using measurement of ultraviolet-absorbance (on-line), blood urea, dialysate urea and ionic dialysance2006In: Nephrology Dialysis Transplantation, ISSN 0931-0509, Vol. 21, no 8, p. 2225-2231Article in journal (Refereed)
    Abstract [en]

    Background. An on-line monitoring system for dialysis dose calculations could make it possible to provide an adequate dialysis dose that is consistently given to haemodialysis (HD) patients. The aim of this study was to compare dialysis dose (Kt/V) using four different methods and their sensitiveness to a reduction in clearance.

    Methods. Six patients were monitored on-line with ultraviolet (UV)-absorbance at a wavelength of 297 nm in three consecutive dialysis sessions during 1 week. During the last treatment, the clearance was reduced by 25% by decreasing the blood flow. For the determination of UV-absorbance, a spectrophotometer was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through a flow cuvette. The equilibrated Kt/V (eKt/V) estimated by UV-absorbance was compared with eKt/V from the ionic dialysance method using the on-line clearance monitor (OCM) and the appurtenant software dose-calculation tool DCTool (Fresenius Medical Care, Germany), eKt/V calculated from the dialysate-urea slope and with eKt/V from pre- and post-dialysis blood-urea samples as reference.

    Results. The study demonstrates that the sensitiveness to clearance reduction is similar in the four methods compared for eKt/V. When the different methods were compared, the mean eKt/V of UV-absorbance was 1.21 ± 0.20, blood 1.30 ± 0.21, dialysate 1.32 ± 0.21 and OCM (using the DCTool) 1.31 ± 0.21. The standard deviation was of the same magnitude.

    Conclusion. The UV-method gives a similar response to clearance reduction compared with the other methods when comparing dialysis dose. The high sampling rate by continuous monitoring of UV-absorbance allows evaluation of the clearance process during dialysis and gives immediate feedback to on-line adjustments.

  • 23.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Fridolin, Ivo
    Centre of Biomedical Engineering, Tallinn Technical University, Tallinn, Estonia.
    Magnusson, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Ultra violet absorbance on-line measurement utilized to monitor clinical events during haemodialysis2006In: Journal of Renal Care, ISSN 1755-6678, E-ISSN 1755-6686, Vol. 32, no 3, p. 141-146Article in journal (Refereed)
    Abstract [en]

    Background: On-line monitoring systems of the spent dialysate, used to estimate dialysis dose, have been developed with different instrumentation during the last two decades. The routine use of an on-line monitoring system has been suggested to provide to give an adequate dialysis dose to the haemodialysis (HD) patients. The aim of this study was to show that monitoring the spent dialysate using UV-absorbance may bring new information about the clearance process. Methods: 108 HD treatments distributed among 16 clinical stable patients were monitored on-line using ultra violet (UV) absorbance. For the measurement of UV-absorbance a spectrophotometer was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through a flow cuvette. The UV-absorbance curves were examined in combination with the recorded observations of events that occurred during the studied treatments.Results: The study demonstrates that UV-absorbance visualizes different kind of events such as hypotension, conductivity alarms, restricted flow in artery needle blood pump stop that often occur during dialysis treatment.Conclusion: An on-line UV-monitoring system with a high sampling rate makes it possibility to identify variations in dialysis clearance of different origin and gives feedback after performing interventions during a dialysis session

  • 24.
    Uhlin, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Holmar, Jana
    Tallinn University of Technology, Estonia .
    Yngman-Uhlin, Pia
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Fridolin, Ivo
    Tallinn University of Technology, Estonia .
    DIALYSDOSEN UPPSKATTAD MED NY MARKÖR - BETA 2-MIKROGLOBULIN (β2M)2012Conference paper (Other academic)
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