Cyclosporin-related nephrotoxicity in children with nephrotic syndrome

Ganesan, Varadarajan; Milford, David V.; Taylor, Carol M.; Hulton, Sally‐Anne; Parvaresh, S.; Ramani, Pramila

doi:10.1007/s00467-001-0810-1

Cited by 19 publications

(15 citation statements)

References 3 publications

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“…Data published by other authors show a CsAN incidence varying from 17% to 79% of patients; most of these were treated with CsA for shorter periods. In two groups of patients with a mean duration of CsA treatment longer than 3 years (3.36 and 3.38 years, respectively) the CsAN incidence was significantly higher (75% and 79%, respectively) [12,13]. Moreover, in these patients CsAN was more severe than in our children.…”

Section: Discussioncontrasting

confidence: 63%

“…Numerous reports have shown CsA treatment to be effective in children with long-lasting NS [3,4,5,6,7,8,9,10,11,12,13] and to induce remission in steroid-resistant NS (SRNS) [14,15,16]. Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity.…”

Section: Introductionmentioning

confidence: 98%

“…Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. CsA-related lesions have been described with variable incidence (from 17% to 79%) in several series of pediatric and adult patients [6,7,10,12,13], and trough levels are commonly used to monitor the CsA blood concentration. The factors responsible for the development of CsAN remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

et al. 2004

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Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2-6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2-6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6-5.8) and 276.6 ng/ml (range 162-346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P <0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P <0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2-3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored.

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Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

et al. 2004

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“…Cyclosporine-related nephrotoxicity, which is characterized by arteriolopathy (arteriolar hyalinosis and hyperplasia), with or without striped interstitial fibrosis and tubular atrophy [23,24], is the most important factor limiting the long-term or high-dose use of cyclosporine [25][26][27][28][29]. One study reported that 2 years of treatment with cyclosporine in a dose that maintained the trough level at 100 ng/ml caused tubulointerstitial changes in seven of 13 patients with steroid-dependent nephrotic syndrome [29].…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome

et al. 2009

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We conducted a prospective, multicenter trial to evaluate the efficacy and safety of a 12-month course of cyclosporine in children with steroid-resistant nephrotic syndrome (SRNS). Thirty-five patients were enrolled, of whom 28 had minimal change or diffuse mesangial proliferation (MC/DMP), and seven had focal segmental glomerulosclerosis (FSGS). All patients received cyclosporine and prednisolone; patients with FSGS additionally received methylprednisolone pulse therapy (MPT). The dose of cyclosporine was adjusted to maintain a trough level of 120-150 ng/ml during the initial 3 months of treatment, followed by 80-100 ng/ml during months 4-12. The primary end point was the remission rate at month 12. Remission was achieved in 23 of 28 (82.1%) patients in the MC/DMP group and in six of the seven (85.7%) patients in the FSGS group. Follow-up renal biopsies were performed in 26 patients (nine at month 12, 17 at month 24), and cyclosporine-related nephrotoxicity was detected in one (3.8%). Major adverse events comprised severe bacterial infections (two patients) and posterior reversible encephalopathy syndrome (one patient). In conclusion, a high remission rate was achieved in our patient cohort using a combined cyclosporine/ prednisolone treatment regimen in children with SRNS who had MC/DMP and a combined cyclosporine/prednisolone plus MPT regimen in children who had FSGS.

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“…Numerous studies have documented the prevalence of CsAN in patients who were treated for idiopathic nephrotic syndrome. Since 1986, Ͼ200 follow-up biopsies in patients who were treated with CsA for SDNS have been reported in the literature (1,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). These studies are difficult to compare because they vary in the number of biopsies, underlying renal pathology, duration of follow-up, dosages of CsA, and criteria to define CsAN.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Cyclosporin A Nephrotoxicity in Children with Steroid-Dependant Nephrotic Syndrome

Kengne-Wafo¹,

Massella²,

Diomedi-Camassei

et al. 2009

Clinical Journal of the American Society of Nephrology

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Cyclosporin-related nephrotoxicity in children with nephrotic syndrome

Cited by 19 publications

References 3 publications

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome

Risk Factors for Cyclosporin A Nephrotoxicity in Children with Steroid-Dependant Nephrotic Syndrome

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