Three Decades of Progress in Treating Childhood-Onset Lupus Nephritis

Abstract

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. 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. 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. 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.