Neurocognitive Function in Pediatric Dialysis

Background

The association between neurologic dysfunction and kidney disease was recognized over 40 years ago when a correlation between the frequency of slow waves on EEG and serum creatinine was first described in adults with kidney failure. A decade later, numerous studies demonstrated that up to 65% of children with CKD show signs of developmental delay. The subsequent recognition of neurocognitive effects of aluminum-induced neurotoxicity was so important that it led to major modifications in the treatment regimens of these patients and resulted in the elimination of an important confounder in the relationship between CKD, its therapy and neurocognitive abnormalities. As management of neonatal and childhood-onset CKD with dialysis and renal transplant improved survival in children significantly, the presence and clinical significance of early-onset neurocognitive deficits in these patients became increasingly apparent.

It is well known that any chronic or significant clinical illness, including CKD, can seriously disrupt the normal process of neurocognitive development seen in children. However, kidney disease may represent a unique subset of chronic illness that leads to a profound impact on childhood neurocognitive development when compared to some other conditions. A systematic review of studies reporting the magnitude of the impact of chronic illness on neurocognitive development looked at children with cystic fibrosis, hemophilia A, ESRD, and end-stage liver disease. It showed that children with cystic fibrosis and hemophilia A did not appear disadvantaged by their illness when compared to children with chronic liver and kidney disease. The authors concluded that despite optimal management, the latter two cohorts show a mild cognitive deficit when compared to population norms.

Risk Factors

Not only is the uremic milieu unique in its ability to produce acute changes in mental status and cognitive functioning, but also numerous studies have demonstrated clinically a significant neurodevelopmental delay in children with CKD. The concurrent presence of severe electrolyte abnormalities, chronic metabolic acidosis, uncontrolled hypertension, renal osteodystrophy, chronic anemia, and malnutrition in CKD has a significant impact on growth and neurodevelopment in children. Other contributing risk factors include the age of onset of renal disease, the duration of illness, presence of genetic or chromosomal disorders, multisystem disease, the need for renal replacement therapy (RRT), as well as the modality used and the psychosocial environment at home. This was demonstrated in a study of 29 children with CKD, which showed that significantly lower IQ and memory function was associated with increased severity of disease, longer duration of illness, and younger age at onset.

Spectrum of Neurocognitive Abnormalities

The neurodevelopmental abnormalities associated with renal disease can range from severe disorders including seizures, hyper- and hypotonia, myoclonus, dyskinesia, microcephaly, and profound neurocognitive delays, to more subtle changes such as sleep disturbance, poor school performance, and changes in memory and executive function. In infants and toddlers who develop CKD at an early age, delays have been reported in both motor and cognitive domains. Studies have estimated that about 25% of patients of infants and toddlers who develop severe renal disease will demonstrate evidence of various developmental delays. In addition, in a prospective cohort study of 319 children with CKD, low total academic achievement was seen in about one-third of the children, with mathematics having the lowest distribution of achievement scores. Additionally, up to a third of children may experience various forms of sleep disturbances, including restless leg syndrome, insomnia, and excessive daytime somnolence.