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

BACKGROUND

Depression is closely linked to neuroinflammation, and in chronic kidney disease, the accumulation of uremic toxins (UTs) may promote neuroinflammatory processes through the activation of inflammatory pathways.

OBJECTIVE

The objective of this longitudinal study was to evaluate the association between UTs and depressive symptoms in a large, well-characterised cohort of non-dialysed adults with chronic kidney disease, a population in which this relationship had not yet been investigated.

METHODS

The Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort comprised 3033 CKD stage 2-5 patients with 5 years of follow-up. Changes over time in depressive symptoms were assessed on the Center for Epidemiologic Studies Depression (CESD) scale. Mixed models were used to examine associations between the change in the CESD score and baseline levels of the UTs phenylacetylglutamine (PAG), indoxyl sulphate (IS), indole-3-acetic acid (IAA), p-cresyl sulphate, kynurenine, kynurenic acid and trimethylamine N-oxide.

FINDINGS: 2165 patients were included (median age: 68 years; mean estimated glomerular filtration rate (eGFR): 35 mL/min/1.73 m²; median baseline CESD score: 7; mean follow-up time: 4.0 years). After adjustment for confounders, the CESD score was found to have increased by 0.11 (0.04 to 0.18) points per year. A doubling in PAG level was associated with an additional increase of 0.06 (0.01 to 0.18) points per year in the CESD. A doubling in IS and IAA levels was associated with a higher mean CESD score (0.20 (0.01 to 0.39) for IS and 0.28 (0.05 to 0.50) for IAA) but not with the score's change over time.

CONCLUSION

PAG was significantly associated with changes in CESD score over time. Higher IS and IAA levels were linked to higher mean scores. Further studies are needed to confirm these results and to determine whether lowering serum UT levels would help to manage depressive symptoms in patients with CKD.

CLINICAL IMPLICATIONS: Further research is needed to clarify the role of UTs; a better understanding could uncover novel metabolic pathways and inform new therapeutic strategies to complement the management of depressive symptoms.