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.

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

“…Our study has few limitations, including that none of the patient had NIH-CI scores > 6. Nonetheless, our cohort is representative of other pediatric LN cohorts [51, 52], and all biomarker relationships and changes observed in our cohort were very likely due to LN, rather than comorbid conditions affecting the kidney. This is different from studies in adults with LN, who often suffer from other chronic system diseases that promote renal scarring, such as hypertension, diabetes, and atherosclerosis.…”

Advances in the care of children with lupus nephritis

“…A prospective randomized trial showed comparable outcomes between CSA and CYC in children (50). Retrospective data in children support the efficacy of sequential induction therapy with MMF followed by CSA for proliferative LN (51).…”

“…While 90% of cSLE patients with class V LN in cSLE achieve renal remission, only 76% can maintain remission despite low dose oral corticosteroids and/or maintenance immunosuppression such as AZA or MMF (88,89). The rate of kidney flares due to SLE is 25-50% on therapy (51,84,89). Besides class IV LN, risk factors for development of ESKD include male gender, black race, hypertension, nephrotic syndrome, anti-phospholipid antibodies, high glomerular staining for MCP-1, chronicity on biopsy, poor response to induction therapy, and occurrence of nephritic kidney flare (23,87).…”

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study

“…18,28 The MPA-cyclosporine combination was demonstrated to be an effective induction therapy with a satisfactory safety profile. [29][30][31][32] Owing to unsatisfactory remission rates of standard management for LN endorsed by the ACR/EULAR, prospective studies are still required to verify the efficacy of MPA combination therapy. 22,27 In the present study, renal pathologic findings were not predictive of clinical remission.…”