Cyclosporin A for the treatment of severe Henoch-Sch�nlein glomerulonephritis

Abstract

We evaluated the efficacy of cyclosporin A (CyA) for treating pediatric patients with severe Henoch-Schönlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria. Seven pediatric HSP-GN patients (5 boys, 2 girls) were treated with CyA, with a mean age of 10.6 years at diagnosis (range 7.2-15.2 years) and mean follow-up times of 6.0 years (range 4.4-8.9 years) from diagnosis and 5.2 years (range 3.4-7.7 years) from the beginning of the CyA treatment. All had developed nephrotic-range proteinuria within 1-3 months of the HSP diagnosis. A renal biopsy was performed on all the patients, and two showed rapidly progressive glomerulonephritis. They all received additional angiotensin converting enzyme inhibitor medication and one to three types of immunosuppressive treatment had been tried in five of the seven patients before CyA was initiated at a mean interval of 0.7 years after diagnosis (range 0.1-2.0 years). All the patients responded to the CyA treatment within a mean of 1.4 months (range 1 week to 4 months). Four patients achieved a stable remission and had been without CyA treatment for a mean of 3.7 years (range 2.9-5.3 years) by the end of the follow-up. Three patients seemed to become CyA dependent, since they developed proteinuria when the treatment was stopped. CyA treatment had been started significantly earlier ( P=0.045) in the former group (mean 0.2 years, range 0.1-0.3 years) than in the latter (mean 1.5 years, range 1.2-2.0 years). Renal function was preserved in all patients, the glomerular filtration rate, plasma cystatin C, serum albumin, and serum creatinine being within normal limits at the end of the follow-up. We conclude that CyA treatment for severe treatment-resistant HSP-GN is promising, since four of the seven patients enjoy stable remission and all have retained their renal function after a mean follow-up of 6.0 years. However, some patients seem to develop CyA-dependent nephritis.

Cyclosporin A therapy for Henoch–Schönlein nephritis with nephrotic-range proteinuria

“…In our study, like those of Ronkainen et al and Shin et al [6,7], all patients responded to the CyA treatment at a mean of 1.8 months (range 1 week to 3.5 months). Our study's protocol was somewhat different from those of other previous studies because we did not use methylprednisolone pulse therapy or other immunosuppressive agents such as cyclophosphamide or azathioprine.…”

“…All our patients were carefully followed during the treatment, in which the blood CyA level was maintained at 50-150 ng/ml during the entire period. This level of CyA is the safest and lowest trough level compared with other studies [6,7]. The ideal duration of CyA treatment for HSN patients is not known.…”

“…According to Ronkainen et al [6], among 7 pediatric HSN patients (nephrotic-range proteinuria) treated with CyA, 4 patients achieved stable remission after a mean follow-up of 6.0 years. According to Shin et al [7], 6 of their 7 patients with nephrotic syndrome achieved stable remission after a mean follow-up of 5.5 years.…”

“…However, to date, the management of severe Henoch-Schönlein nephritis (HSN) has remained controversial. A few recent studies have suggested that cyclosporin A (CyA) might have a beneficial effect in children with severe HSN, but the numbers of patients included are limited [6][7][8]. We analyzed clinical outcomes of 29 HSN patients with nephrotic-range proteinuria treated with CyA.…”

Treatment of Different Types of Vasculitis

“…cyclophosphamide, cyclosporin A), plasmapheresis, anticoagulant agents and antiplatelet agents is controversial. Glucocorticoids in combination with each of these treatments can be effective in patients with severe nephritis (Flynn JT et al, 2001;Hattori M et al, 1999;Kawasaki Y et al, 2004;Ronkainen J et al, 2003;Scharer K et al, 1999;Someya T et al, 2004;Tanaka H et al, 2003;Tarshish P et al, 2004;Wyatt RJ & Hogg RJ, 2001;Zaffanello M et al, 2007). Administration of Factor XIII, tonsillectomy, and dapsone may be useful for the patients with Henoch-Schönlein purpura, but the evidence concerning efficacy is insufficient.…”