Depression's Implied Bilateral Link With Chronic Kidney Disease Progression

Depression has a substantial effect on patients with chronic kidney disease (CKD), with new research suggesting it may accelerate disease progression, particularly in the early stages.1

Additionally, the findings highlight a disproportionate diagnosis of depression in patients with end-stage kidney disease, with investigators suggesting there may be an increased psychological burden as kidney function declines.1

“From a clinical standpoint, implementing systematic depression screening could meaningfully change CKD care pathways,” wrote study investigator Abdullah Al-Mamun, PhD, an Assistant Professor in the Department of Pharmaceutical Systems and Policy from the West Virginia University School of Pharmacy, and colleagues.1

The previous literature in CKD has linked the disease burden to increased depression instances, and, in turn, adverse health outcomes. A recent study paired CKD and social frailty, especially in patients in advanced stages undergoing hemodialysis, with an increased risk of depression. Meanwhile, another study found CKD patients with depressive symptoms were more likely to initiate dialysis or experience all-cause mortality, pointing to a potential link between mental health and disease trajectory. Another study observed an association of depressive symptoms with a 2.25-fold higher risk of progression to dialysis over 3 years.1,2,3,4

In this retrospective cohort analysis, Al-Mamun and colleagues aimed to further evaluate the association between depression and CKD, especially beginning with early stages. They extracted data from the TriNetX electronic medical record database of patients with a CKD diagnosis. The primary objective included key independent variables such as diagnosis of depression or anxiety, identified by ICD codes. Secondary objectives were CKD stages ≥ 3, 4, and 5, as defined by Kidney Disease Improving Global Outcomes (KDIGO).1

The primary outcome was progression to kidney disease, with an eGFR < 60 ml/min/bsa and > 40% decline in eGFR from the initial screening, while the secondary outcome was diagnosis of depression.1

The study included adults ≥ 18 years of age with baseline CKD at > 1 year of follow-up data. The primary objective cohort was dichotomized into depression or no depression, and the secondary objective cohort was categorized by CKD stages.1

In Kaplan-Meier curve analysis, investigators found faster kidney disease progression in patients with depression compared to patients without (P <.0001). In the adjusted Cox model, depression was significantly associated with an increased risk of kidney disease progression 1.94 (95% Confidence Interval [CI], 1.77–2.11, P < .05).1

Among the 3 CKD stage groups, the survival probability decreased most rapidly for patients in stage 5, followed by stage 4, and then stage ≤3, with investigators positing it indicates patients in more advanced stages of CKD are more likely to develop depression earlier. Additionally, the differences between the survival curves for the CKD stages were statistically significant (P <.0001), suggesting a strong association between CKD stage and the time to depression onset.1

Furthermore, investigators reported an increased risk of developing depression in patients in stage 4 compared to those in stage ≤3 (Hazard Ratio [HR], 1.26 [1.17–1.35]; P < .05), and those in Stage 5 had an even higher increase in risk (HR, 1.38 [1.23–1.54]; P <.05).1

“The findings of this study underscore a significant association between depression and CKD progression, particularly in the earlier stages,” concluded investigators. “Our results show that patients with a diagnosis of depression following their CKD diagnosis had a higher likelihood of kidney disease progression compared to those without depression.”1

References

1. Jeun KJ, Brothers T, Khaled Shawwa, Al-Mamun MA. A retrospective cohort study on the bidirectional association between depression and chronic kidney disease. Frontiers in Nephrology. 2026;5. doi:https://doi.org/10.3389/fneph.2025.1743594

2. Gabriela D, Luma Geraigire, Ferreira S, et al. Predictors of Social Frailty and Depression in Brazilian Patients With Chronic Kidney Disease: A Cross‐Sectional Study. Geriatrics and gerontology international/Geriatrics & gerontology international. Published online January 1, 2026. doi:https://doi.org/10.1111/ggi.70317

3. Shen Y, Chen Y, Huang S, Yao X, Kanwar YS, Zhan M. The Association between Symptoms of Depression and Anxiety, Quality of Life, and Diabetic Kidney Disease among Chinese Adults: A Cross-Sectional Study. International Journal of Environmental Research and Public Health. 2023;20(1):475. doi:https://doi.org/10.3390/ijerph20010475

4. Zhang Z, He P, Liu M, et al. Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function. Clinical Journal of the American Society of Nephrology. 2021;16(6):889-897. doi:https://doi.org/10.2215/cjn.18441120