Cognitive Function and Uremic Toxins after Kidney Transplantation: An Exploratory Study

Abstract

Background: Cognitive functions are altered in patients with chronic kidney disease. However it is suggested that cognitive functions, at least partially, improve after kidney transplantation. A possible cause for this improvement could be the reduction of uremic retention solutes after transplantation. This study assessed the association between the changes in uremic toxin concentration with the changes in cognitive function in patients after kidney transplantation. Methods: 10 kidney transplant recipients were included and compared to 18 controls (9 patients on hemodialysis, and 9 patients with CKD stage 4 or 5 (eGFR < 30ml/min/1.73m 2 not on dialysis). An extensive neuropsychological assessment, covering the five major cognitive domains, that is, memory, attention and concentration, information processing speed, abstract reasoning, and executive function, was done before, at one week and three months after transplantation. Similarly assessments of the 18 matched control patients were performed longitudinally over a period of three to five months. Concentrations of sixteen uremic retention solutes namely indoxylglucuronide, pcresylglucuronide, phenylglucuronide, CMPF, indoxyl sulphate, p-cresyl sulphate, hippuric acid, phenyl sulphate, kynurenine, tryptophan, kynurenic acid, tyrosine, indole-3-acetic acid, phenylalanine, trimethylamine N-oxide (TMAO), and phenylacetylglutamine were measured in serum samples collected at the time of the neuropsychological assessments. Results: A significant improvement in cognitive function was only found in the processing speed domain, and observed in both transplant patients as well as CKD patients. No significant differences between transplant patients and the control groups were seen in the other cognitive domains. As expected, the serum concentration of most uremic toxins decreased significantly within one week after kidney transplantation. Conclusions: There was no significant improvement in cognitive function that could be specifically related to kidney transplantation in the first 3 months after the procedure. These data do not support the notion that uremic toxins exert an immediate effect on cognitive function.

Psychosocial Burden of Itch among Renal Transplant Recipients

“…Its prevalence and intensity does not seem to be influenced by graft function, electrolyte disturbances, chronic inflammation, or comorbidities [ 9 ]. Moreover, it was also proven that successful kidney transplantation with good renal function may significantly lower the levels of uremic toxins often responsible for itch development [ 39 , 41 ]. Due to unclear pathogenesis, the treatment of CKD-aI remains an important challenge and its outcome is frequently unsatisfactory both for patients and clinicians.…”

“…Their accumulation and major impact on both large vessels and brain microcirculation may favor the occurrence of cerebrovascular diseases, leading to cognitive disorders and dementia [ 44 ]. Although successful renal transplantation with a functioning graft would significantly lower the level of uremic toxins [ 41 ], it is still unclear if the cerebral changes are reversible [ 41 ]. Moreover, Hsu et al [ 45 ] described a higher prevalence of depression in CKD patients with lower albumin and indoxyl sulfate (IS) levels.…”

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

“…The small number of patients might explain the lack of a significant change. However, the researchers observed clear changes in the serum levels of uraemic toxins after transplantation—even within 3 days [ 72 ], when previously reported a marked reduction after 1 month after kidney transplantation [ 52 , 53 ].…”

Uremic encephalopathy

“…Kidney transplantation also effectively reduces the concentrations of a multitude of uremic toxins as demonstrated in 10 recipients of a living-kidney transplant. 120 Most changes were observed within three days after surgery with reductions in the concentrations of indoxyl sulfate, hippuric acid and p-cresyl sulfate. The study also evaluated cognitive function in five domains, including memory, attention, information processing speed, J o u r n a l P r e -p r o o f abstract reasoning, and executive function.…”