title: Long-term outcomes with multi-targeted immunosuppressive protocol in children with severe proliferative lupus nephritis.
abstract: We have previously reported the one-year outcomes of 16 children with severe proliferative lupus nephritis (LN) who were treated using a multi-targeted induction protocol based on intravenous (IV) pulse methylprednisolone (MP), mycophenolate mofetil (MMF) and cyclosporine (CSA). This study examined the long-term renal outcomes of these 16 children, followed up for a median duration of 9.2 years (range 5.8-14.2 years). Primary treatment outcome was complete renal remission. Secondary outcomes included patient and renal survival as well as relapse-free and event-free survival. All patients achieved complete renal remission within 24 months (median 8.7 months, range 4.0-24.0 months). Comparing clinical and laboratory parameters at induction and last follow-up, respectively, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (25.4 ± 8.7 vs. 0.4 ± 0.8), serum complement C3 (47 ± 21 vs. 107 ± 27 mg/dL), estimated glomerular filtration rate (eGFR) (72 ± 57 vs. 109.7 ± 43 ml/min/1.73 m2) and urine protein (6.97 ± 7.09 vs. 0.2 ± 0.02 g/day/1.73 m2) improved significantly (p < 0.05). Kaplan-Meier survival analysis showed a cumulative ten-year renal relapse-free survival of 73.3% when considering relapses with severe proteinuria >1 g/day/1.73 m2. Cumulative probability that hospitalization would not be required was 93.8% at one year, and 71.4% at ten years. Our multi-targeted protocol for induction and maintenance therapy in Asian children with severe proliferative LN resulted in good long-term patient survival and renal preservation, with a good safety profile.
authors.affiliation: Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: E
authors.initials: E
authors.lastname: Aragon
authors.affiliation: Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: L P
authors.initials: LP
authors.lastname: Resontoc
authors.affiliation: Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chan
authors.affiliation: Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.
authors.forename: Y W
authors.initials: YW
authors.lastname: Lau
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: P H
authors.initials: PH
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: H L
authors.initials: HL
authors.lastname: Loh
authors.affiliation: Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore Department of Pediatrics Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: K H
authors.initials: KH
authors.lastname: Ng
authors.affiliation: Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore Department of Pediatrics Yong Loo Lin School of Medicine, National University of Singapore, Singapore hui_kim_yap@nuhs.edu.sg.
authors.forename: H K
authors.initials: HK
authors.lastname: Yap
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008181:Lupus Nephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D020551:Pulse Therapy, Drug; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D012720:Severity of Illness Index; D012846:Singapore; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008775:Methylprednisolone
keywords: Systemic lupus erythematosus; children; cyclosporine; mycophenolate mofetil; proliferative lupus nephritis; renal survival