ORIGINAL RESEARCH article
Front. Nephrol.
Sec. Clinical Research in Nephrology
A Retrospective Cohort Study on the Bidirectional Association Between Depression and Chronic Kidney Disease
Provisionally accepted
- 1West Virginia University, Morgantown, United States
- 2University of Rhode Island, Kingston, United States
- 3University of Rhode Island College of Pharmacy, Kingston, United States
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Rationale and Objectives: Depression has been associated with worse clinical outcomes in individuals with chronic kidney disease (CKD), yet its influence on kidney disease progression in earlier CKD stages remains underexplored. Thus, this study investigates the role of depression on CKD progression by stages, and bidirectional relationship using real-world data. Methods: This was a retrospective cohort analysis. Data was extracted from the TriNetX EMR database from 2007 to 2022. Patients (>18 years of age) with diagnosis of CKD were selected for the study. Key independent variables were diagnosis of depression or anxiety, identified by ICD codes, for the primary objective, and CKD stages (i.e., >3, 4, and 5) defined by KDIGO for the secondary objective. Primary outcome was progression to kidney disease (eGFR < 60 ml/min/bsa and > 40% decline in eGFR from the initial screening), and the secondary outcome was diagnosis of depression. Kaplan-Meier analysis and Cox proportional hazards model were used to evaluate the relationship between the dependent and independent variables while adjusting for covariates (sex, race, ethnicity, and age). Results: Depression was significantly associated with a higher risk of kidney disease progression (HR=1.94 [1.77–2.11], p<0.001). Among patients with CKD, patients with CKD stages 4 and 5 had significantly higher risks (HR=1.26 [1.17–1.35] and 1.38 [1.23–1.54], p<0.001) of new diagnosis of depression than those in stage ≤3, respectively. These associations remained statistically significant after matching and adjusting for age, sex, race, and comorbidities. Conclusion: Depression significantly accelerates CKD progression and patients with stage 5 CKD had the highest risk of developing depression. Our study advocates for integrating frequent mental health screenings for patients with CKD. This could improve patient outcomes and minimize negative consequences associated with depression.
Keywords: Anxiety, Chronic kidnel disease, Depression, disease progression, electronic healt records
Received: 10 Nov 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Jeun, Brothers, Shawwa and Al-Mamun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Todd N Brothers
Mohammad Al-Mamun
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