Cyclosporine in patients with steroid-resistant nephrotic syndrome: An open-label, nonrandomized, retrospective study

Gian Marco Ghiggeri, Paolo Catarsi, Francesco Scolari, Gianluca Caridi, Roberta Bertelli, Alba Carrea, Simone Sanna-Cherchi, Francesco Emma, Landino Allegri, Giovanni Cancarini, Gian Franco Rizzoni, Francesco Perfumo

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Steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis has emerged as a leading cause of end-stage renal failure (ESRF) in children and adults. In the past decade, immunosuppressive drugs such as cyclosporine (CsA) and cyclophosphamide have been introduced for the treatment of SRNS, but data on long-term clinical outcome (over years) are lacking. The current study considered the clinical outcome of patients with SRNS who had been treated with CsA for >2 years. The primary objective was to evaluate renal function after years of treatment compared with nontreated or CsA-resistant patients. A secondary objective was to identify renal effects related to the use of CsA, with a major emphasis on renal fibrosis. In this open-label, nonrandomized, retrospective study, the outcomes of patients of all ages with sporadic SRNS who had been followed up for >2 years (between 1970 and 2002) at 4 Italian clinical institutions were evaluated. Preliminary molecular screenings for genes encoding proteins of the slit-diaphragm (eg, podocin, nephrin, α-actinin) were performed to exclude inherited forms of sporadic SRNS. A total of 157 patients were studied; mutations were found in 18 patients (11%). Of the remaining 139 patients (84 men, 55 women; median [interquartile range (IQR)] age at onset of proteinuria, 12 [4-32] years), 84 (60%) were nontreated and 55 (40%) were treated with CsA. Of these 55 treated patients, 35 (64%) were found to be resistant (ie, persistence of proteinuria after 2 months) or intolerant (ie, malignant hypertension or worsening of renal function), and CsA was withdrawn. The median (IQR) durations of follow-up for CsA-resistant and nontreated patients were 41 (23-92) and 48 (28-106) months, respectively. Twenty patients (36%) were responsive to CsA and were followed up for a median (IQR) of 81 (47-115) months. Progression Lo ESRF occurred in 10% of CsA-responsive patients versus 60% of CsA-resistant patients and 62% of nontreated patients (P = 0.002). No sign of renal fibrosis related to drug toxicity was observed in renal biopsies performed at 5-year intervals. This retrospective analysis of SRNS documented a persistent antiproteinuric effect of long-term CsA (>2 years) in the absence of renal fibrosis. Although sensitivity to CsA was associated with normal renal function, resistance or intolerance was associated with progression to ESRF These data suggest that CsA may have a role in the treatment of patients with SRNS.

Original languageEnglish
Pages (from-to)1411-1418
Number of pages8
JournalClinical Therapeutics
Issue number9
Publication statusPublished - Sep 2004


  • cyclophosphamide
  • cyclosporine
  • end-stage renal failure
  • focal segmental glomerulosclerosis
  • nephrotic syndrome

ASJC Scopus subject areas

  • Pharmacology

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