Depression in chronic kidney disease: Particularities, specific mechanisms and therapeutic considerations, a narrative review

Abstract

Introduction: Depression is highly prevalent during chronic kidney disease (CKD) with studies suggesting prevalence rates ranging from approximately one-quarter to half of CKD patients. CKD and depression have a bidirectional relationship, each disorder aggravating the other, leading to more complex and challenging patient management. Depression during CKD is multifactorial and is associated with increased risk of adverse events and hospitalization. Methods: We conducted a narrative review of experimental and observational studies in animals and humans, as well as meta-analyses, to explore specific mechanisms of depression in CKD and its treatment. Results: In depression the gut-brain axis is central. CKD leads to an accumulation of gut-derived uremic toxins. One key factor is the accumulation of tryptophan-derived uremic toxins like kynurenines or indoxyl sulfate, whose serum concentration increases progressively with the stage of CKD (up to 100-fold in stage 5), and which plays an important role in depression mechanisms, by activating aryl hydrocarbon receptor, decreasing brain concentrations of serotonin by approximately 40 %, increasing brain inflammation, via activation of microglia and astrocytes and release of TNFα, IL-6 and NO. Randomized controlled studies found limited or no benefits of antidepressants for depressive symptoms in CKD and hemodialysis patients. Conclusion: Chronic inflammation, in relation to uremic toxin accumulation during CKD, seems to be a complex but important mechanism for treatment resistance in depression. Future research should consider inhibitors of uremic toxins inhibitors and anti-inflammatory molecules as potential therapeutic agents, to improve the prognosis of depression in CKD patients.