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Article

Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention

by
Michail Evgeniou
1,
Paul Perco
2,3,
Fabian Eibensteiner
1,
Markus Unterwurzacher
1,
Andreas Vychytil
4,
Rebecca Herzog
1,*,† and
Klaus Kratochwill
1,2,*,†
1
Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
2
Delta 4 GmbH, Alserstrasse 23, 1080 Vienna, Austria
3
Department of Internal Medicine IV, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
4
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2025, 14(11), 3733; https://doi.org/10.3390/jcm14113733
Submission received: 16 April 2025 / Revised: 15 May 2025 / Accepted: 23 May 2025 / Published: 26 May 2025

Abstract

Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in PD and to identify novel drug combinations that may target dysregulated molecular mechanisms associated with PD’s pathophysiology. Methods: We analyzed clinical records from 702 PD patients spanning 30 years, encompassing over 5500 prescription points. Using network-based modeling techniques, we assessed drug co-prescription patterns, clinical outcomes, and longitudinal treatment trends. To explore potential drug repurposing opportunities, we constructed a molecular network model of PD based on a consolidated transcriptomics dataset and integrated this with drug–target interaction information. Results: We found commonly prescribed drugs such as furosemide, sucroferric oxyhydroxide, calcitriol, darbepoetin alfa, and aluminum hydroxide to be integral components of PD patient management, prescribed in over 30% of PD patients. The molecular-network-based approach found combinations of drugs like theophylline, fluoxetine, celecoxib, and amitriptyline to possibly have synergistic effects and to target dysregulated molecules of PD-related pathomechanisms. Two further distinct categories of drugs emerged as particularly interesting in our study: selective serotonin reuptake inhibitors (SSRIs), which were found to modulate molecules implicated in peritoneal fibrosis, and vascular endothelial growth factor (VEGF) inhibitors, which exhibit anti-fibrotic properties that are potentially useful for PD. Conclusions: This comprehensive exploration of drug co-prescriptions in the context of PD-related pathomechanisms provides valuable insights for opening future therapeutic strategies and identifying new targets for drug repurposing.
Keywords: peritoneal dialysis; drug combination; network analysis; biological networks; drug repurposing peritoneal dialysis; drug combination; network analysis; biological networks; drug repurposing

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MDPI and ACS Style

Evgeniou, M.; Perco, P.; Eibensteiner, F.; Unterwurzacher, M.; Vychytil, A.; Herzog, R.; Kratochwill, K. Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention. J. Clin. Med. 2025, 14, 3733. https://doi.org/10.3390/jcm14113733

AMA Style

Evgeniou M, Perco P, Eibensteiner F, Unterwurzacher M, Vychytil A, Herzog R, Kratochwill K. Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention. Journal of Clinical Medicine. 2025; 14(11):3733. https://doi.org/10.3390/jcm14113733

Chicago/Turabian Style

Evgeniou, Michail, Paul Perco, Fabian Eibensteiner, Markus Unterwurzacher, Andreas Vychytil, Rebecca Herzog, and Klaus Kratochwill. 2025. "Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention" Journal of Clinical Medicine 14, no. 11: 3733. https://doi.org/10.3390/jcm14113733

APA Style

Evgeniou, M., Perco, P., Eibensteiner, F., Unterwurzacher, M., Vychytil, A., Herzog, R., & Kratochwill, K. (2025). Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention. Journal of Clinical Medicine, 14(11), 3733. https://doi.org/10.3390/jcm14113733

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