The Limits of the Dichotomy Between Responders and Nonresponders in Chronic Kidney Disease
8 affiliations
- 1Nephrology and Dialysis Unit, “Cannizzaro” Emergency Hospital, 95126 Catania, Italy
- 2Advanced School of Ultrasound in Nephrology, Italian Society for Ultrasound in Medicine and Biology (SIUMB), 00192 Catania, Italy
- 3Nephrology and Dialysis Unit, “St. Antonio Abate” Hospital, 91016 Trapani, Italy
- 4Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “A. Moro”, 70121 Bari, Italy
- 5Department of Medicine, University of Verona, 37131 Verona, Italy
- 6Nephrology and Dialysis Unit, Department of Internal Medicine, “C. e G. Mazzoni” Hospital, 63100 Ascoli Piceno, Italy
- 7Department of Medicine and Health Sciences, University of Trento, 38122 Trento, Italy
- 8Nephrology and Dialysis Unit, Santa Chiara Hospital, ASUIT, 38122 Trento, Italy
Abstract
Background/Objectives: In contemporary chronic kidney disease care, determining whether an individual patient is benefiting from treatment is increasingly complex. Disease-modifying therapies may influence multiple clinical domains, and these effects may emerge with different magnitudes and time courses. Nevertheless, treatment response is frequently summarized using binary labels such as ‘responder’ and ‘nonresponder’, often on the basis of a single biomarker at a single time point. Such classifications are useful when associated with a clearly defined outcome, threshold, and assessment window, but may be misleading when interpreted as the patient’s overall response to therapy. Methods: This study examines the limitations of responder–nonresponder dichotomy, considering biological and analytical variability, treatment exposure, adherence, concomitant therapy, intercurrent events, and layered treatment. A domain-by-time framework for interpreting treatment-associated trajectories is proposed. Results: The framework first considers the nature and timing of observed changes, then assesses their interpretability considering treatment exposure and clinical context, and finally evaluates the strength of their attribution to treatment. It provides a conceptual, patient-level reporting and research framework that complements existing estimands principles, validated surrogate endpoints, and disease-specific response criteria. Conclusions: The proposed framework aims to improve the description and interpretation of treatment-associated trajectories without implying individual causal treatment effects. Its reproducibility and clinical utility require prospective evaluation.
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BibTeX
@article{granata2026limits,
title = {{The Limits of the Dichotomy Between Responders and Nonresponders in Chronic Kidney Disease}},
author = {Antonio Granata and Rosario Maccarrone and Alfio Edoardo Giuffrida and Leonardo Spatola and Francesco Pesce and Settimio Di Gregorio and Matthias Zeiler and Yuri Battaglia},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15208095},
url = {https://www.mdpi.com/2077-0383/15/20/8095},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Limits of the Dichotomy Between Responders and Nonresponders in Chronic Kidney Disease
AU - Antonio Granata
AU - Rosario Maccarrone
AU - Alfio Edoardo Giuffrida
AU - Leonardo Spatola
AU - Francesco Pesce
AU - Settimio Di Gregorio
AU - Matthias Zeiler
AU - Yuri Battaglia
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15208095
UR - https://www.mdpi.com/2077-0383/15/20/8095
AB - Background/Objectives: In contemporary chronic kidney disease care, determining whether an individual patient is benefiting from treatment is increasingly complex. Disease-modifying therapies may influence multiple clinical domains, and these effects may emerge with different magnitudes and time courses. Nevertheless, treatment response is frequently summarized using binary labels such as ‘responder’ and ‘nonresponder’, often on the basis of a single biomarker at a single time point. Such classifications are useful when associated with a clearly defined outcome, threshold, and assessment window, but may be misleading when interpreted as the patient’s overall response to therapy. Methods: This study examines the limitations of responder–nonresponder dichotomy, considering biological and analytical variability, treatment exposure, adherence, concomitant therapy, intercurrent events, and layered treatment. A domain-by-time framework for interpreting treatment-associated trajectories is proposed. Results: The framework first considers the nature and timing of observed changes, then assesses their interpretability considering treatment exposure and clinical context, and finally evaluates the strength of their attribution to treatment. It provides a conceptual, patient-level reporting and research framework that complements existing estimands principles, validated surrogate endpoints, and disease-specific response criteria. Conclusions: The proposed framework aims to improve the description and interpretation of treatment-associated trajectories without implying individual causal treatment effects. Its reproducibility and clinical utility require prospective evaluation.
SN - 2077-0383
ER -