Depressive symptoms in chronic kidney disease: the hidden role of uremic toxins

By
Hélène Levassort
Sophie Liabeuf
Julie Boucquemont
Gaye Hafez
Solene M Laville
Celine Lange
Luc Frimat
Christian Combe
Denis Fouque
Maurice Laville
Christian Jacquelinet
Yves-Edouard Herpe
Lucile Montalescot
Islam Amine Larabi
Natalia Alencar de Pinho
Ziad A Massy
Jean-Claude Alvarez
Marion Pépin
on behalf of CKD-REIN
June 24, 2026
0 min

Bmj Mental Health

Overview

This study investigates the relationship between uremic toxins and depressive symptoms in patients with chronic kidney disease (CKD).

Background

Depression is prevalent in chronic kidney disease (CKD) patients, with rates significantly higher than the general population. The accumulation of uremic toxins (UTs) in CKD may contribute to neuroinflammation and depressive symptoms.

Data Highlights

Parameter	Value
Median Age	68 years
Mean eGFR	35 mL/min/1.73 m²
Median Baseline CESD Score	7
Mean Follow-Up Time	4.0 years
CESD Score Increase per Year	0.11 (0.04 to 0.18)
PAG Score Increase per Doubling	0.06 (0.01 to 0.18)
IS Score Increase per Doubling	0.20 (0.01 to 0.39)
IAA Score Increase per Doubling	0.28 (0.05 to 0.50)

Key Findings

2165 patients were included in the study with a median age of 68 years.
The CESD score increased by 0.11 points per year after adjusting for confounders.
A doubling in phenylacetylglutamine (PAG) levels was associated with an additional increase of 0.06 points in the CESD score per year.
Higher levels of indoxyl sulfate (IS) and indole-3-acetic acid (IAA) were linked to higher mean CESD scores.
PAG was significantly associated with changes in CESD scores over time.

Clinical Implications

Further research is needed to clarify the role of uremic toxins in relation to depressive symptoms in CKD patients.

Conclusion

Further studies are needed to confirm these results and to determine whether lowering serum uremic toxin levels would help manage depressive symptoms in patients with CKD.