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Abstract
Background In children with proliferative lupus nephritis, response to induction treatment is based on clinical parameters. The added benefit of repeat kidney biopsy in defining therapy response remains unclear. Emerging adult data suggests a discordancy between clinical and histological outcomes. In children, we hypothesize that histologic reassessment after induction therapy correlates better with clinical remission.
Methods A single-center retrospective observational cohort study was conducted in childhood-onset proliferative lupus nephritis with a repeat biopsy after 5-9 months of induction therapy from 2007 to 2019. LN response was determined clinically. Histologic activity and damage were calculated using National Institutes of Health activity and chronicity indices. Lupus nephritis class transformation and changes in the degree of immune complex deposition were determined. Descriptive statistics and comparison tests were used before and after induction treatment.
Results A total of 44 patients were identified. Complete clinical response was achieved in 43% (19/44) after induction and 69% (29/42) at one year. None of the complete responders after induction had histologic activity index of > 2 on repeat biopsy (figure 1). Activity index after induction in complete responders (median 1, range 0-2) was lower than in partial or non-responders (median 2, range 0-10) (p-value < 0.005). Complete clinical response was associated with transformation to a non-proliferative class in 79% (15/19) and a reduction in immune complex deposition in 68% (13/19) on repeat biopsy.
Conclusions Unlike adult-onset lupus nephritis, clinical and histologic remission are more congruent after induction therapy in childhood-onset disease. There was good correlation between clinical response and activity index.
Lay Summary Lupus nephritis can cause kidney failure. The need to balance risks and benefits of immunosuppression requires stringent monitoring. In adults with lupus, available diagnostics are insufficient to gauge response to initial ”induction” therapy and repeat biopsy studies are necessary to rigorously test novel biomarkers. Here we show that repeat biopsy in children performed 1/2 year into therapy correlates well with clinical response, but there is a subset of children with sub-clinical scarring that would be missed without repeat biopsy - this subset may be at risk long-term for kidney failure.
Findings at first biopsy (baseline, at time of nephritis diagnosis) and repeat biopsy (5-7 months into therapy) stratified by clinical response at time of repeat biopsy (CR, complete response; PR, partial response; NR, no response). Shown are medians (lines), means (large circles), and ranges (activity index scored 0 to 24 and chronicity index scored 0 to 12 based on ISN/RPS schema).
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