Secondary resistance to cyclosporin A in children with nephrotic syndrome

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.

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“…None of our patients developed the secondary resistance to CyA that has been reported in patients with NS [17].…”

Section: Discussionmentioning

confidence: 65%

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

Ronkainen

Autio–Harmainen

Nuutinen

2003

Pediatric Nephrology

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“…In these patients, CyA administration results in remission of proteinuria. However, because of the nephrotoxic properties of CyA, the treatment should be carefully monitored by measuring its serum level [2,4].…”

Section: Discussionmentioning

confidence: 99%

“…It also activates the sympathetic system, stimulates production of thromboxane and endothelin-1, and reduces prostaglandin production. This leads to increased arterial pressure [3,4,5]. Angiotensin II in the kidneys stimulates the production of transforming growth factor (TGF-b1) both by local parenchymal cells and by lymphoid tissue [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Another important application of CyA is in steroid-dependent (SDNS) or steroid-resistant nephrotic syndrome. In children it is used in focal segmental glomerulosclerosis (FSGS) with proteinuria [3,4]. CyA decreases the pressure inside the renal glomerulus by contracting the afferent arteriole, which results in improvement of the bioelectric properties of the basement membrane and reduction in proteinuria [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor-?1 in nephrotic syndrome treated with cyclosporine and ACE inhibitors

Wasilewska

Zoch-Zwierz

2004

Pediatr Nephrol

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The aim of the study was to assess urinary transforming growth factor (TGF)-beta1 in children with steroid-dependent nephrotic syndrome (SDNS) treated with cyclosporine A (CyA) and ACE inhibitors (ACEI). The study involved 24 children (14 boys and 10 girls) with SDNS and signs of focal segmental glomerulosclerosis. The children were treated with prednisone, CyA, and ACEI. All children were examined four times: A during relapse of proteinuria, before treatment with CyA and ACEI, and B after 3 months, C 6 months, and D 12 months of treatment. The control group consisted of 20 healthy children of the same age. The urinary TGF-beta1 level was determined by ELISA (R and D Quantikine). The serum CyA level was measured by monoclonal antibody fluorescence polarization immunoassay. Prior to CyA treatment, the urinary TGF-beta1 level was the highest (135.61+/-38.31 pg/mg creatinine). During CyA treatment, TGF-beta1 was reduced to 117.96+/-81.57 after 3 months, to 80.26+/-49.52 after 6 months, and to 44.00+/-31.83 pg/mg creatinine after 12 months, but it was still higher than in the control group. At 3 months there was a positive linear correlation between urinary TGF-beta1 and proteinuria (r=0.654, P<0.01). These results indicate that the urinary TGF-beta1 level increases in proportion to proteinuria during relapse of NS. Treatment with CyA and ACEI also influences urinary TGF-beta1, which is still higher after 12 months of treatment than in healthy children.

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“…Kemper et al reported that SDNS can recur in patients despite CSA maintenance therapy [36], and despite its efficacy, the majority of patients relapse if CSA is stopped [12,[37][38][39].…”

Section: Cyclophosphamide or Cyclosporine A For Treatment?mentioning

confidence: 99%

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

et al. 2008

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A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6 +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.

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Secondary resistance to cyclosporin A in children with nephrotic syndrome

Cited by 20 publications

References 23 publications

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

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

Transforming growth factor-?1 in nephrotic syndrome treated with cyclosporine and ACE inhibitors

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

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