Feasibility of Ratio-Based Biomarkers in Peritoneal Dialysis Effluent for Non-invasive Monitoring

 

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Feasibility of Ratio-Based Biomarkers in Peritoneal Dialysis Effluent for Non-invasive Monitoring

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Xin
Wang
Xiaoling Wang xiaoling.wang@rriny.com Fresenius Medical Care Clinical Research New York United States *
Nadja Grobe Nadja.Grobe@rriny.com Fresenius Medical Care Clinical Research New York United States -
Hasib Absar hasib.absar@rriny.com Fresenius Medical Care Clinical Research New York United States -
Mark Kakembo mark.kakembo@rriny.com Fresenius Medical Care Clinical Research New York United States -
Xin Wang xin.wang@rriny.com Fresenius Medical Care Clinical Research New York United States *
Lela Tisdale lela.tisdale@rriny.com Fresenius Medical Care Clinical Research New York United States -
Manuela Stauss-Grabo manuela.stauss-grabo1@freseniusmedicalcare.com Fresenius Medical Care Clinical Research New York United States -
Peter Kotanko peter.kotanko@mssm.edu Icahn School of Medicine at Mount Sinai Department of Medicine and Nephrology New York United States -
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Peritoneal dialysis (PD) effluent is a readily accessible biofluid enriched with patient-derived biomolecules that may reflect peritoneal and systemic physiology. However, interpreting absolute biomolecule concentrations is often confounded by multiple factors, including PD modality, dialysate glucose concentration, dwell volume and duration, body position, ultrafiltration volume (UFV), peritoneal membrane transport characteristics, and more. To mitigate these variabilities, we explored the feasibility of ratio-based biomarkers in PD effluent, which may offer a normalization-inherent and robust strategy to monitor biological and treatment-related dynamics in PD patients.

We analyzed 110 non-peritonitis PD effluent samples from 17 patients (2 to 21 samples each). Initial dialysate glucose ranged from 1.5% to 2.5%, with dwell times between 60 to 720 minutes. Twenty samples from nine patients were obtained during standardized peritoneal equilibration tests; others were self-collected at home. Metabolomic profiling was performed using untargeted liquid chromatography tandem mass spectrometry (LC–MS/MS; Agilent 6546 Q-TOF). Albumin and total protein were measured by a chemical analyzer (Horiba Pentra C400). Longitudinal trajectories were analyzed to evaluate intra-patient stability, and coefficients of variation (CV) were calculated across all patients to assess inter-patient variability.

We identified and semi-quantified 150 metabolites in PD effluent. Together with albumin and total protein, seven clinically relevant ratios were derived: kynurenine/tryptophan (Kyn/Trp), arginine/asymmetric dimethylarginine (Arg/ADMA), arginine/citrulline (Arg/Cit), octanoylcarnitine/carnitine (C8/C0), glutamine/alanine (Glu/Ala), cystine/cysteine (CySS/CyS), and albumin/globulin (Alb/Glob). Among these, Alb/Glob is an absolute concentration ratio, whereas the others were calculated from relative MS intensities and serve as semi-quantitative indices. Collectively, these ratios reflect pathways including tryptophan degradation, nitric oxide metabolism, fatty acid oxidation, amino acid transamination, and redox balance.

Despite changes in PD prescription, dwell time, modality, glucose concentration, and UFV, most ratios remained stable within individuals. Representative longitudinal trends (Figure 1A–B) show minimal fluctuations over 400–800 days in both APD and CAPD patients. At the cohort level (Figure 1C), median CVs were <25% for most ratios, indicating strong temporal consistency. Glu/Ala and Kyn/Trp showed the lowest CV, suggesting robustness against effluent variability. C8/C0 and CySS/CyS showed moderate dispersion, possibly reflecting oxidative stress influences.

figure 1

This study demonstrates the feasibility of ratio-based biomarker analysis in PD effluent. Despite procedural variability, metabolite and protein ratios remained stable, supporting their potential as reliable, non-invasive indicators of metabolic, redox, and nutritional status in PD patients. Further validation against ratio-based biomarkers and clinical outcomes is warranted to establish their value for longitudinal monitoring and personalized PD management.

Kewords