Discordance Between Clinical and Pathologic Findings on Post-Induction Kidney Biopsy in Pediatric Patients with Proliferative Lupus Nephritis

Introduction Systemic lupus erythematosus (SLE) diagnosed during childhood is associated with higher rates of mortality and lupus nephritis compared to adult-onset SLE. Lupus nephritis (LN) itself is independently associated with higher mortality and proliferative lupus nephritis (ISN/RPS Class III and Class IV) is associated with an increased risk of progression to end stage kidney disease. Once a diagnosis of LN has been confirmed on initial kidney biopsy, the utility and optimal timing for subsequent biopsies in LN has not been established. There is known discordance between the clinical parameters used to diagnose LN and the histopathologic classification. Often clinicians are uncertain about the impact of titration in immunosuppression when relying solely on clinical parameters. Purpose To explore the utility of a subsequent kidney biopsy in guiding treatment of LN after induction therapy and to determine if the standard clinical signs of kidney disease can be used to target repeat kidney biopsy to the patients most likely to benefit from the information obtained. Methods This study was a single center retrospective cohort study of SLE patients who underwent kidney biopsy for lupus nephritis at Rady Children’s Hospital, San Diego (RCHSD). Subjects were stratified based on their Childhood Arthritis and Rheumatology Research Alliance (CARRA) renal response into complete renal response (CRR) and incomplete renal response (IRR) groups at the time of the second biopsy. Demographic data were not distributed normally, therefore a non-parametric Wilcoxon paired t-test was used for comparison of continuous variables. The Chi squared test was used for categorical data between remission groups. Single predictor and multiple predictor logistic regression models were utilized to assess the relationship between clinical factors and histologic findings on second biopsy. Results At the time of second biopsy, both groups had lower SLEDAI scores compared to first biopsy, and CRR group had significantly lower SLEDAI scores compared to IRR group. Of the other clinical markers assessed at time of second biopsy, including age, dsDNA, serum C3, change in C3 between biopsies, and serum C4, none were found to be significantly different between the two groups. Findings on second biopsy influenced immunosuppressive therapy decisions in both CRR and IRR groups. Conclusions Currently available clinical markers of disease remission in lupus nephritis after induction therapy are insufficient to identify children with ongoing evidence of persistent proliferative nephritis. Follow up kidney biopsy is low risk and can be used to guide therapy in children with SLE and nephritis.