Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome.

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.

Long-term linear growth of children with severe steroid-responsive nephrotic syndrome.

The present study was designed to evaluate the risk of permanent linear growth impairment in a selected group of 42 children with steroid-dependent nephrotic syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome (FRNS). Longitudinal height measurements were available in all patients from the onset of the disease for a mean follow-up of 11.7+/-3.5 years. During the prepubertal period, patients lost 0.49+/-0.6 height SD score (HtSDS) ( P<0.001). Twenty-three patients have reached their final height with an average loss of 0.92+/-0.8 HtSDS from the onset of their disease ( P<0.001) and 0.68+/-0.7 from their target HtSDS ( P<0.001). The pubertal growth spurt was mildly delayed in male but not female patients. Steroid therapy, calculated as the mean duration of prednisone (PDN) treatment or as the average cumulative PDN dose, was the only predictor of poor growth evolution. Partial catch-up growth occurred after PDN withdrawal. Children with early onset NS and adolescent patients, who were still receiving PDN after the age of 9 years in girls and 11 years in boys, were at higher risk for HtSDS loss. In conclusion, children with severe steroid-responsive NS are at risk of permanent growth retardation secondary to prolonged courses of steroid treatment.