Three decades of progress in treating childhood-onset lupus nephritis.

Background And Objectives: Childhood-onset lupus nephritis (LN) carries a worse renal prognosis compared with adults. Controlled treatment trials in children are lacking. We compared renal and patient survival in a cohort of pediatric patients followed over 3 decades.

Design, Settings, Participants, & Measurements: A retrospective analysis was conducted on 138 patients with childhood-onset systemic lupus erythematosus from 1980 to 2010. The core cohort included 95 with severe LN: 28 progressed to end-stage renal disease (ESRD group) whereas 67 did not (no-ESRD group). Patients were stratified into four "eras" according to the introduction of the primary immuno-suppressive drug: era 1: triple oral therapy with corticosteroids (CS), cyclophosphamide (CYC), and azathioprine (AZA); era 2: intravenous CYC; era 3: mycophenolate mofetil (MMF) ± CYC; era 4: rituximab (RTX) ± CYC ± MMF.

Results: Mean age at diagnosis was 12.3 ± 2.9 years with median follow-up of 5 years. Poor renal function (estimated GFR < 60 ml/min per 1.73 m(2)) and nephrotic proteinuria at diagnosis imparted a poor prognosis. Increasing proteinuria correlated with progression of kidney disease. The addition of MMF in era 3 improved 5-year renal survival from 52% to 91% and overall patient survival from 83% to 97%. African-American ethnicity was associated with significant risk for progression to ESRD whereas Hispanic ethnicity conferred an advantage. Infection and cardiovascular disease were the primary causes of patient demise.

Conclusions: Renal and patient survival in childhood-onset LN has improved during the past 3 decades with progressive treatment regimens. Future trials in children are very much warranted.