Background/Purpose: Children with lupus nephritis (LN) are at risk for cognitive impairment due to effects on the brain from systemic inflammation and from potential effects of chronic kidney disease (CKD). We aimed to determine the risk for neurocognitive dysfunction for children with LN compared to children with other etiologies of glomerular CKD, hypothesizing a higher risk for those with LN, and examined the relationship of cognitive function to quality of life (QOL).

Methods: We conducted a cross-sectional analysis of the Chronic Kidney Disease in Children (CKiD) cohort, a 54-center prospective observational study of pediatric CKD patients with mild/moderate renal dysfunction. We determined neurocognitive outcomes using baseline measures after study entry for standardized tests of intelligence, academic achievement, attention/inhibitory control, memory, and executive function. QOL was measured using parent and child reports of the Pediatric Inventory of Quality of Life Core Scales 4.0. We used inverse probability weighting in a logistic model for propensity score analysis to achieve balance between children with LN and those with other glomerular CKD for the following variables: age, sex, height, race, ethnicity, maternal education, glomerular filtration rate, proteinuria, systolic blood pressure, and anemia. We used linear regression models to: i) compare neurocognitive outcomes between exposure groups, adjusting for prednisone use (yes/no), and testing for an interaction between prednisone use and LN, and ii) test for an association between cognitive function and QOL.

Results: Compared to subjects with other glomerular CKD (n=171), those with LN (n=34) had shorter median CKD duration (1.6 vs 4.0 years) and higher prednisone use (59% vs 23%). In adjusted analyses, subjects with LN had higher intelligence (p=0.07), academic achievement (p=0.03), and better performance for attention (p=<0.01) and inhibitory control (p=0.07) (Table). There were no differences for the other cognitive measures, and no significant interactions between prednisone use and LN. Prednisone use was independently associated with better achievement (p=0.05), but worse attention (p=0.01). Lower executive function was associated with worse parent (p<0.001) and child-reported QOL (p<0.001), and lower attention (p<0.01) and inhibitory control (p<0.01) with worse child-reported QOL.

Conclusion: Contrary to our hypothesis, children with LN early in their disease course have comparable or better cognitive function than their peers with other glomerular CKD, possibly due to shorter disease duration and/or more immunosuppressive treatment. Further study should examine the association of disease duration and immunosuppression in cognitive function for children with LN, as well as strategies to mitigate adverse effects of cognitive dysfunction on QOL in children with CKD.