Journal Article

Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome

Catherine Morgan, Banu Sis, Maury Pinsk and Verna Yiu

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 9, pages 2860-2865
Published in print September 2011 | ISSN: 0931-0509
Published online February 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq813
Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome

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Background. Steroid-dependent, steroid-resistant or frequently relapsing nephrotic syndrome carries a poor prognosis, including progression to renal failure. There are a number of studies confirming the efficacy of FK506 in steroid-resistant or steroid-dependent nephrotic syndrome. Although the use of this medication is becoming more common, we know very little about the potential nephrotoxicity when used in nephrotic syndrome.

Method. We retrospectively reviewed the characteristics and biopsy findings of 11 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with FK506. Two sequential biopsies were evaluated for the change in interstitial fibrosis, measured by a quantitative stereological method, and the change in arteriolar hyaline thickening, tubular atrophy and interstitial fibrosis, graded according to Banff criteria.

Results. There was an increase in interstitial fibrosis (P = 0.005), with a median absolute change in the per cent volume density between initial and follow-up biopsies of 1.8% [interquartile range (IQR) 3.9%]. Median percentage change in volume density of interstitial fibrosis, relative to volume density of interstitial fibrosis prior to initiating FK506, was 93% (IQR 138%). Banff scores for interstitial fibrosis and tubular atrophy also increased following tacrolimus therapy (P = 0.04 for both). Average FK506 trough level over the treatment period was significantly associated with change in fibrosis (Spearman's rho = 0.67 and P = 0.02).

Conclusions. This is some of the first histological data concerning tacrolimus nephrotoxicity in childhood nephrotic syndrome. Although the role of the natural progression of the underlying disease in the observed change is not definitively clear, the changes seen are in keeping with the known nephrotoxic effects of FK506 demonstrated in renal transplant. This increase is small when presented as a median change. However, there were a number of children who had a larger change in fibrosis. The factors predictive of interstitial fibrosis while on FK506 are not well defined; the findings from this study suggest that FK506 level may be a factor. Given the observations and limitations of the few published studies, there is an obvious need for further study in a large multicenter prospective trial.

Keywords: calcineurin toxicity; FK506; FSGS; interstitial fibrosis; treatment-resistant nephrotic syndrome

Journal Article.  4057 words.  Illustrated.

Subjects: Nephrology

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