C-MANNOSYL TRYPTOPHAN ASSOCIATED SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS ASSESSED USING SPENT DIALYSATE MEASUREMENTS

 

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https://storage.unitedwebnetwork.com/files/1099/05119f0f7e168cb970705c8aaf0fe057.pdf
C-MANNOSYL TRYPTOPHAN ASSOCIATED SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS ASSESSED USING SPENT DIALYSATE MEASUREMENTS

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Joosep
Paats
Joosep Paats joosep.paats@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia *
Liisi Leis liisi.leis@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia - North Estonia Medical Centre Centre of Nephrology Tallinn Estonia
Annika Adoberg annika.adoberg@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia - North Estonia Medical Centre Centre of Nephrology Tallinn Estonia
Jana Holmar jana.holmar@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
Kai Lauri kai.lauri@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
Kristjan Pilt kristjan.pilt@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
Jürgen Arund jurgen.arund@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
Merike Luman merike.luman@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia - North Estonia Medical Centre Department of Health Technologies Tallinn Estonia
Risto Tanner risto.tanner@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
Ivo Fridolin ivo.fridolin@taltech.ee Tallinn University of Technology Department of Health Technologies Tallinn Estonia -
 
 
 
 
 

Haemodialysis (HD) is the most common form of kidney replacement therapy prescribed for end-stage kidney disease (ESKD) patients. However, morbidity and mortality of ESKD patients on chronic HD is still high and of significant concern with five-year survival probability reported to be below 50 % in some studies. A novel biomarker C-mannosyl tryptophan (CMW), also sometimes referred to as C-glycosyltryptophan, has previously been strongly and independently associated with kidney disease progression, overall and cardiovascular mortality in different patient groups. Therefore, CMW could also be a valuable indicator of clinical outcomes for ESKD patients.

This study aimed to explore the potential of estimating pre-dialysis serum CMW concentrations (S_CMW) of chronic HD patients from CMW concentrations in spent dialysate (D_CMW) samples, collected in the beginning of HD treatment, and assessing survival probability of HD patients based on estimated S_CMW concentrations from spent dialysate.

In total, 76 ESKD patients were monitored during four dialysis sessions with pre-defined treatment settings. In all, we collected 304 predialysis serum samples from arterial lines of HD machine and 304 spent dialysate samples from the drain outlet of HD machine (7 min after the start of HD session) to determine and evaluate average baseline S_CMW concentration of each patient over four sessions. As a reference, high-performance liquid chromatography was used to determine CMW concentrations in serum and spent dialysate samples. Subsequently, a linear regression model was used to estimate S_CMW concentrations (S_CMW(D_HPLC)) from D_CMW concentrations, including prescribed blood flow rate and total spent dialysate flow rate as additional input parameters of the regression model. Next, ROC and Kaplan-Meier survival analyses were performed to study 5-year follow-up survival of patients based on estimated S_CMW concentrations (S_CMW(D_HPLC)) using MedCalc® Statistical Software version 22.020 (MedCalc Software Ltd, Ostend, Belgium).

A total of 76 ESKD patients undergoing HD, with a median age of 66.5 (interquartile range: 54.0-76.3) years, of whom 22% female, were monitored from 2018 to 2023. At the beginning of the study, the patients had an average ± SD S_CMW concentration of 2.70 ± 0.69 μmol/L, BMI of 26.1±5.3 kg/m2, median dialysis vintage of 35 (17-71) months. Of the patients 48 were anuric and 28 patients had median residual diuresis of 750 (350-1200) mL.

Out of the 76 patients, 34 (44.7 %) were deceased at follow-up of five years and 18 (23.7%) patients were excluded from the survival analysis due to receiving kidney transplantation during the follow-up period.

The predicted S_CMW concentrations from spent dialysate (S_CMW(D_HPLC)) were strongly (r2=0.845) correlated to HPLC determined S_CMW values (Figure 1).

Scatter plot for HPLC determined serum CMW concentrations (S_CMW) plotted against predicted serum CMW concentrations from spent dialysate CMW concentrations S_CMW (D_HPLC).

The predicted S_CMW concentrations from spent dialysate (S_CMW(D_HPLC)) had a statistically significant relationship with the 5-year survival of the HD patients (Figures 2 & 3) with the serum CMW cut-off levels at 2.17 μmol/L (Kaplan-Meier P = 0.0001). Hazard ratio with 95% CI in the group of patients with S_CMW (D_HPLC) > 2.17 μmol/L was identified to be 3.82 (1.92-7.59).

Receiver operating characteristic (ROC) curve for 5-year patients survival based on regression model estimated serum CMW concentrations , sensitivity = 73.5 specificity = 70.8.


In conclusion, this study demonstrates the possibility to assess C-mannosyl tryptophan associated survival of HD patients based on spent dialysate measurements. As it is feasible to optically monitor CMW levels in spent dialysate, implementation of this non-invasive monitoring approach could be possibly used to assess long-term outcomes of patients.


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