**2. Optical online monitoring of dialysis dose**

#### **2.1 Background of optical dialysis dose monitoring**

Optical methods in dialysis dose monitoring started approximately 40 years ago with the development of the HPLC technique, which utilizes UV/Visible (Vis) spectroscopic data for analysis [13–16]. HPLC was utilized for molecule separation and identification of contents in plasma, urine and spent dialysate [17–20]. The "era of uremic toxins search" was born.

Applying standard laboratory photometers to measure solute removal during haemodialysis (HD) was first introduced by Boda and coworkers [21] who demonstrated an exponential decline of UV absorption in spent dialysate at wavelength 210 nm. The introduction of light-fiber optics and the developments of monochromator-detector in the mid-1980s and early-1990s, respectively, entailed near infrared spectroscopy (NIRS) becoming more powerful for scientific research. First, at the end of the 20th century, both UV- and NIRS-techniques were developed forward as practical tools applied for HD dose monitoring.

A Hungarian group published the first report about how UV transmittance of the spent dialysate can be measured at 254 nm, believed to be the best wavelength to

#### *Optical Online Monitoring of Uremic Toxins beyond Urea DOI: http://dx.doi.org/10.5772/intechopen.110080*

monitor the efficacy of HD, [22]. Besides, there was concluded that the hardly diffusible components had a higher elimination rate compared to the removal rate of small, more freely diffusible constituents. Nearly two decades later, a work aiming to monitor the dialysis liquid during HD by UV absorbance was presented by Vasilevski et al. [23]. They also discussed UV extinction as an indicator of nucleic acid metabolism [24]. Almost simultaneously, in 2001, independent studies about online monitoring of solutes in dialysate using UV absorbance were published [6, 25], studying the possibility to monitor removal of different uremic solutes in the spent dialysate, and further firstly describing, as an illustrative example, how to estimate urea Kt/V from UV absorbance. The first clinical study, incorporating the UV-technology with a real clinical application, Kt/V calculation, was reported by Uhlin et al. [7]. A fruitful and exciting collaboration between Uhlin, Fridolin and co-workers within the field of optical dialysis dose monitoring has been followed. During the last decade, in connection with commercialization of the UV-technology for dialysis dose monitoring, new interest has appeared in the optical field. Some works, by the groups from Japan, related to spectroscopic analysis of uremic substances in dialysate have been presented [26, 27] and additionally some papers from St. Petersburg [28]. Validation of a clinical prototype device [29] and the commercially available UV absorbance dialysis dose monitor have been also presented [30]. The UV absorbance method as an alternative method to measure small-solute clearance is mentioned in DOQI clinical practice guideline for haemodialysis adequacy [31]. Moreover, the clinical care guidelines are available to interpret the real-time haemodialysate UV absorbance patterns to optimize solute clearance, troubleshoot problematic absorbance patterns and intervene during an individual treatment as needed [32].

#### **2.2 Overview of optical principles in spectroscopy**

Optical dialysis monitoring techniques utilize mostly phenomena described by the optics of biological fluids. Biological fluids include all kinds of fluids made by living organisms like urine, lymph, saliva blood, semen, mucus, gastric juice, aqueous humor, etc. Spent dialysate can also be categorized as a biological fluid derived by filtering the compounds usually less in size than 50,000 Dalton from blood through a dialyzer membrane into the pure dialysate containing water and electrolytes.

From the perspective of optics, biological tissues and fluids can be divided into two large classes: strongly scattering (opaque) tissues and fluids, such as skin, brain, vessel walls, blood, milk lymph and eye sclera, and weakly scattering (transparent) tissues and fluids such as crystalline lens, cornea, vitreous humor, aqueous humor of the front chamber of the eye [33] and spent dialysate. For the second class, the Beer–Lambert law is often applicable [34]. In this section, we will present a short description of the electromagnetic spectrum, some basic principles about photon propagation in biological fluids, Beer–Lambert law and examples of how this could be utilized as a measurement.

#### *2.2.1 Electromagnetic radiation*

Electromagnetic (EM) radiation used to be classified by wavelength into radio-, microwave, infrared, visible region, ultraviolet and x- and gamma-rays. The characteristics of EM radiation depend on its wavelength. An illustration of the EM spectrum range is shown in **Figure 1**. Infra-red (IR) is per definition EM radiation with a wavelength range between 760–0.5 mm, Vis 390–770 nm and UV 100–400 nm. The

#### **Figure 1.**

*Illustration of the EM spectrum range.*

EM spectrum of UV can be subdivided in a number of ways. The draft ISO standard on determining solar irradiances [35, 36] describes the following ranges relevant to dialysis optical monitoring:


"Light" is usually defined as visible EM radiation of the entire EM spectrum where the human eye is sensitive [37–40], but the term light is often extended to adjacent wavelength ranges that the eye cannot detect [40]. Spectroscopy can detect a much wider region of the EM spectrum than the Vis range and a common laboratory spectrophotometer can detect wavelengths from 200 to 2500 nm.
