The Limits of the Dichotomy Between Responders and Nonresponders in Chronic Kidney Disease

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.