Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Abstract

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins’ putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.

Oral hygiene practice, dental profile and dental service utilization of chronic kidney disease patients

“…CKD patients have been reported to present with xerostomia (dry mouth), candidiasis, alteration in taste, periodontitis, dental caries and tooth loss [6,36]. Taste alteration is commonly reported among CKD patients although the underlying mechanism is not well understood.…”

“…The occurrence of dry mouth may be as a result of fluid restriction, electrolyte imbalance and use of drugs that have xerostomia as side effects. Halitosis has been attributed to poor oral hygiene and uremic smell [36].…”

Tissue Factor, Thrombosis, and Chronic Kidney Disease

“…More than 100 uremic toxins have been identified thus far [ 39 ], and the pathological roles of protein-bound uremic toxins, such as indoxyl sulfate, have been actively studied. Accumulated uremic toxins are involved in CKD progression and complications, including cardiac dysfunction, sarcopenia, and cognitive function [ 19 , 40 , 41 ]. Notably, the relationship between the hemostasis system and uremic toxins in CKD pathogenesis has recently received considerable attention [ 17 , 18 , 19 , 20 ] ( Figure 1 ).…”

Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease

“…Recently, kidney disease has been proposed as a new modifiable risk factor for dementia [2]. It is reported that uremic toxins may have direct neurotoxic (astrocyte activation and neuronal death) and/or indirect action through vascular effects (cerebral endothelial dysfunction, calcification, and inflammation) [3,4]. Due to the endothelial dysfunction, small-vessel pathology has been used to clarify the link between kidney and cerebral microvasculature that share similar anatomical and physiologic features.…”

“…In patients with CKD stages III to V, the relation between kidney and cognitive function was evaluated independently of the vascular risk factors. Among the other factors, the retention of uremic toxins, especially phosphate, has been again presented as a CKDspecific factor, accountable for structural and functional cerebral changes in patients with CKD [3,29]. Finally, the high phosphate level was associated with inflammation, stress, depression, and dementia, including Alzheimer's disease [30].…”