**4.2 Multi-component uremic toxins' intradialytic optical monitoring of spent dialysate**

Several *in vitro* and online studies towards optical multi-component uremic toxins' monitoring have been published by our group during the last 10 years [9, 95–98] *Optical Online Monitoring of Uremic Toxins beyond Urea DOI: http://dx.doi.org/10.5772/intechopen.110080*

**Figure 7.** *Example of a chromatogram of a spent dialysate sample, where peak 9 is indoxyl sulphate. [Reprinted from [92]].*

and by a group from Taiwan [99]. The studies demonstrate that optical dialysis monitoring, based on UV absorbance and fluorescence of spent dialysate, can simultaneously reveal removal patterns of, for example, urea, β2M and IS during various dialysis treatment modalities without any blood or dialysate sampling, **Figure 8**.

A good agreement between chemically and optically estimated solute removal parameters, RR and total removed solute, was achieved. Dialysis modality did not affect the accuracy of optical method, taking into account that β2M was excluded from the analysis in the case of dialysis with low-flux dialyzer [9]. **Figure 9** shows the agreement in RR (%) for urea, β2M and IS between measurements from laboratory and the developed online optical dialysis adequacy sensor (OLDIAS).

#### *4.2.1 Drug interference during the optical dialysis monitoring in spent dialysate*

There have been indications that the administration of some drug chromophores, for example paracetamol (Par), to dialysis patients could disturb the accuracy of the

#### **Figure 8.**

*An example representing real-time concentration profiles for urea, β2M (B2M) and IS during a single dialysis from optical measurements in the spent dialysate in parallel with the discrete concentration values estimated from the laboratory analyses of spent dialysate samples at different time moments.*

#### **Figure 9.**

*A comparison presenting the agreement in RR for urea (Urea), β2M (B2M) and indoxyl sulphate (IS) between measurements from laboratory and the online optical dialysis adequacy sensor (OLDIAS).*

optical methods since a noteworthy contribution of Par and its metabolites to the total UV absorbance was determined at three wavelengths 210, 254 and 280 nm [100], where the latter is used in the commercial monitor [56]. Adoberg et al. confirmed that the administration of Par in large amounts increased the UV absorbance of spent dialysate, which can result in overestimation of concentration and the RR of uric acid (UA) when evaluated by UV absorbance of spent dialysate, using the UV region that overlaps with the Par-absorption spectrum [101]. At the same time, the correlation between the IS concentration and fluorescence in the spent dialysate is not affected by Par administration to dialysis patients, neither is the optical assessment of the RR of IS on the basis of the fluorescence of spent dialysate. **Figure 10** illustrates a representative chromatogram of the spent dialysate of a patient with high Par intake (twice 1 g of Par before dialysis, 1 g during the dialysis session and four times 1 g on the previous day) and the UV absorbance spectra of Par, Par metabolites and UA peaks on the insert.

These limitations could be overcome by using multiparametric optical models that incorporate several UV wavelengths in order to evaluate the removal of UA, and also urea, or using the UV region, such as 295 nm, to minimize the influence of Par.

#### **Figure 10.**

*Characteristic HPLC UV 295 nm chromatogram of spent dialysate of one patient with high Par intake. Insert: UVabsorbance spectra of peaks of uric acid (UA), paracetamol glucuronide (ParG), paracetamol (Par), paracetamol sulphate (ParS), and indoxyl sulphate (IS) [Reprinted from [101]].*

Conventionally prescribed drugs in connection with dialysis treatment did not interfere with the optical monitoring of the treatment [101].

#### *4.2.2 Future directions in optical monitoring*

The future vision of the dialysis optical monitoring technology is moving towards the ability to estimate efficacy measures of several important uremic toxins, for example, **Figure 8** that are linked to morbidity and survival for dialysis patients.

Attempts of optical intradialytic monitoring of AGE's have also been carried out within our group, showing no difference between average of free pentosidine concentrations in the spent dialysate measured by HPLC and models, developed from the full fluorescence spectra [102]. Tryptophan, which originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes, may also be a target for future monitoring. Paats et al. evaluated serum levels and removal during HD and haemodiafiltration (HDF) of tryptophan and tryptophan-derived uremic toxins, indoxyl sulphate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings [103]. High-efficiency HDF resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high-efficiency HDF increased Trp losses [103]. Furthermore, by adding chemical displacers, combining ibuprofen and furosemide, during HDF, the removal of protein-bound uremic toxins can be enhanced [104, 105].

Finally, the technology will be integrated into the dialysis machines of the future for simple handling and easy monitoring over time, **Figure 11**.

#### **Figure 11.**

*An example of a future display on the dialysis machine where multiple performance measures (removal ratio, total removed amount, Kt/V) for β2M (B2M) (Courtesy of Optofluid Technologies OÜ, Estonia, with permission).*
