Effect of Low-Dose Cyclosporine A in the Treatment of Refractory Proteinuria in Childhood-Onset Lupus Nephritis

Abstract

We performed a prospective study to evaluate the efficacy and safety of low-dose cyclosporine A (CSA) treatment in paediatric lupus nephritis refractory to conventional therapy. Seven children with biopsy-proven Class III-IV lupus nephritis were treated with CSA (2-4 mg/kg/day) combined with low-dose prednisone for one year. All patients had failed to achieve sustained proteinuria remission with corticosteroids and cytotoxic drugs. Proteinuria decreased from median value of 2.5 g/24 hours (range, 1.2-4.9) to 0.14 g/24 hours (range, 0.0-0.84) after treatment (P = 0.018). Median values of creatinine clearance and serum creatinine did not change significantly. Median systemic lupus erythematosus disease activity index score decreased from 12 (range, 6-16) to 4 (range, 0-8) at end of treatment (P = 0.027). However, two patients experienced flares of extrarrenal manifestations and complement levels did not improve. Moreover, most patients relapsed with proteinuria within a few months of stopping CSA therapy. Side effects were not significant. In conclusion, low-dose of CSA combined with steroids appears to be useful to reduce proteinuria in paediatric proliferative lupus nephritis refractory to steroids and cytotoxic drugs; however, relapses are common after CSA discontinuation. Further studies are needed to define the precise role of CSA in paediatric lupus nephritis.

Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis

“…As CD154 over-expression has a crucial role in the pathogenesis of SLE, our demonstration that NFAT mediates this over-expression in children renders CsA an attractive potential agent in the treatment of lupus. To date, the published experience with this agent in childhood SLE consists of two prospective studies (44, 45) and an open-randomized comparison of CsA versus corticosteroids plus cyclophosphamide (46), all of which showed varying degrees of improvement in disease manifestations, particularly proteinuria. The lack of a controlled clinical trial of this medication in lupus likely reflects its adverse effect profile, which consists of nephrotoxicity and reversible hypertension.…”

Juvenile systemic lupus erythematosus: Review of clinical features and management

“…Some studies have also shown improvement in proliferative nephritis with the use of cyclosporine and tacrolimus. However, relapses were found to be common after discontinuation [44,45].…”

Pediatric Lupus—Are There Differences in Presentation, Genetics, Response to Therapy, and Damage Accrual Compared with Adult Lupus?

“…HLA DRB1*03:01, DQA1*05:01, and DQB1*02:01 are more common in Caucasians with SLE, again independent of age at disease onset121. Non-MHC loci that have been associated with pediatric SLE and aSLE are the 1858T single nucleotide polymorphism (SNP) of PTPN22, a gene which encodes for the enzyme lymphocyte phosphatase (Lyp) and inhibits T-cell activation116, 122–123. A polymorphism (−28C/G polymorphism) of the RANTES (also CCL5) gene also has been associated with aSLE, and its importance was confirmed in a study of Chinese children with SLE124.…”