## 2 Results  
### Removal of IS and PCS by DVB-PVP and Cellulose Resins: In Vitro Study  
At first, resin adsorption capacity towards IS and PCS was assessed in vitro (Figure 1). DVB-PVP resin adsorbed total IS and PCS to a greater extent than cellulose resin. Indeed, after 6 hours of perfusion, DVB-PVP removed a mean of \(40.9\pm 1.6\) mg of total IS compared to cellulose (\(19.0\pm 6.8\) mg; \(p=0.04\)) and a mean of \(62.6\pm 9.8\) mg of total PCS compared to cellulose (\(38.7\pm 4.8\) mg; \(p=0.04\)) starting from a total amount of \(75.4\) mg of IS and \(115.7\) mg of PCS in the solution (Figure 2 and Table 1).  
Likewise, free portions of IS and PCS were also more efficiently absorbed by DVB-PVP resin compared to cellulose. Indeed, after 6 hours perfusion, DVB-PVP removed a mean of \(8.17\pm 0.48\) mg of free IS and \(10.41\pm 1.30\) mg of free PCS compared to cellulose (\(1.79\pm 0.55\) mg of free IS and \(2.30\pm 0.71\) mg of free PCS, respectively; \(p=0.04\) for both. Table 1). In terms of percentage of the IS and PCS initial amounts removed from the experimental solution, DVB-PVP resin adsorbed, after 6 hours of perfusion, a mean of \(53.7\pm 2.0\%\) of \(0.1\)mM IS, and a mean of \(56.0\pm 4.7\%\) of \(0.177\) mM PCS compared to cellulose resin (\(25.0\pm 9.0\%\) total IS and \(31.7\pm 3.7\%\) total PCS, respectively; \(p=0.04\) for both) (Figure 2, Table 1). Considering the free fractions, DVB-PVP resin reduced free IS of \(66.0\%\pm 4.0\%\) (mean) and free PCS of \(70.0\pm 8.5\%\) (mean) compared to \(15.3\pm 4.9\%\) (mean) reduction in both free IS and PCS by cellulose.  
Figure 1: In vitro experiment. Recirculation of an experimental solution in a closed circuit containing the resin sorbent to be tested. Solution samples to be tested were collected after passing through the resins after 1, 3, and 6 hours.  
In addition, we evaluated the effect of the resins on the variation of IS and PCS albumin binding, and we found that the percentage of IS and PCS albumin binding (%PB) increased during the six hours of perfusion through DVB-PVP, while decreased during six hours of perfusion through cellulose, corresponding to the pH values. Data are reported in Supplementary Materials (Table S1: %PB of IS and PCS, and pH values registered in the experimental solution at start condition and at the end of the considered time points).  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Solutes**} & \multicolumn{4}{c}{**Total Amount**} \\ \cline{2-5}  & & **At start** & **Removed by DVB-PVP** & **Removed by Cellulose** \\ \hline \multirow{2}{*}{Indoxyl sulfate MB, mg-(RR\%)} & Total & 75.4 & 40.9-(54\%) & 19.1-(25\%) \\  & Free & 11.8 & 8.2-(66\%) & 1.7-(15\%) \\ \multirow{2}{*}{p-cresyl sulfate MB, mg-(RR\%)} & Total & 115.7 & 62.6-(56\%) & 38.7-(31\%) \\  & Free & 14.7 & 10.4-(70\%) & 2.3-(15\%) \\ \multirow{2}{*}{BSA MB, g-(RR\%)} & & 126 & 17.7-(14\%) & 10.6-(8\%) \\ \hline \hline \end{tabular}
\end{table}
Table 1: Mean value of the total mass removal after 6 hours passing through the cartridge containing the resin. MB: Mass Balance = (Cfinal-Cinitial) \(\times\) Total Volume – RR (%): Removal Rate = (Cfinal – Cinitial)/Cinitial \(\times\) 100. BSA, bovine serum albumin.  
Figure 2: Amount of total IS and PCS removed from the experimental solution after passing through the cartridge containing the DVB resin and cellulose, respectively, at different time points. Data are expressed as median \(\pm\) SD for Mass Balance = (Cfinal-Cinitial) \({}^{*}\) Total Volume and for RR: Removal Rate = (Cinitial – Cfinal)/Cinitial \({}^{*}\) 100.