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Experience with tacrolimus in children with steroid-resistant nephrotic syndrome.

Butani L, Ramsamooj R - Pediatr. Nephrol. (2009)

Bottom Line: There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings.In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS.Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California Davis Children's Hospital, 2516 Stockton Boulevard, Sacramento, CA 95817, USA. Lavjay.butani@ucdmc.ucdavis.edu

ABSTRACT
Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-beta immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-beta tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels.

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Related in: MedlinePlus

Flow-chart depicting outcomes in study population. CR Complete remission, SRNS steroid-resistant nephrotic syndrome
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Fig2: Flow-chart depicting outcomes in study population. CR Complete remission, SRNS steroid-resistant nephrotic syndrome

Mentions: Final disposition The Tac doses were increased over time as necessary to achieve CR if the patients did not show any acute rise in serum creatinine levels. Dose escalation was at the discretion of the treating nephrologist. At last follow-up, the median (range) Tac doses and trough levels were 0.15 (0.06–0.38) mg/kg per day and 5 (1.8–12.3) ng/mL, respectively. No significant differences were seen in Tac dosing/trough among ethnicities. The mean final Tac trough level in children of Caucasian, Asian, Hispanic and African-American ethnicities was 5.5, 5.6, 7.3 and 4.3 ng/mL, respectively (p = 0.17); the final Tac dose in these same ethnic groups was 0.12, 0.22, 0.14 and 0.08 mg/kg per day, respectively (p = 0.87). Of the 15 children who responded to Tac, nine were able to come off steroids; six remained on steroids due to steroid-responsive relapses (n = 3) or as part of their initial steroid-taper (n = 3), only two of whom were receiving daily prednisolone. The longest steroid-free interval for the nine children who were taken off steroids was a median (range) of 28.5 (0.1–54) months. Seven of the 15 children (47%) had relapses during attempted steroid-taper, of whom six had steroid-responsive relapses. One child, with FSGS, did not go into remission despite daily prednisolone therapy and was taken off Tac. At last follow-up, of the 15 children, 13 were still receiving Tac. The two who were taken off Tac had frequent relapses and were transitioned to other regimens. Figure 2 depicts the outcomes in the children in the form of a flow-diagram.Fig. 2


Experience with tacrolimus in children with steroid-resistant nephrotic syndrome.

Butani L, Ramsamooj R - Pediatr. Nephrol. (2009)

Flow-chart depicting outcomes in study population. CR Complete remission, SRNS steroid-resistant nephrotic syndrome
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697358&req=5

Fig2: Flow-chart depicting outcomes in study population. CR Complete remission, SRNS steroid-resistant nephrotic syndrome
Mentions: Final disposition The Tac doses were increased over time as necessary to achieve CR if the patients did not show any acute rise in serum creatinine levels. Dose escalation was at the discretion of the treating nephrologist. At last follow-up, the median (range) Tac doses and trough levels were 0.15 (0.06–0.38) mg/kg per day and 5 (1.8–12.3) ng/mL, respectively. No significant differences were seen in Tac dosing/trough among ethnicities. The mean final Tac trough level in children of Caucasian, Asian, Hispanic and African-American ethnicities was 5.5, 5.6, 7.3 and 4.3 ng/mL, respectively (p = 0.17); the final Tac dose in these same ethnic groups was 0.12, 0.22, 0.14 and 0.08 mg/kg per day, respectively (p = 0.87). Of the 15 children who responded to Tac, nine were able to come off steroids; six remained on steroids due to steroid-responsive relapses (n = 3) or as part of their initial steroid-taper (n = 3), only two of whom were receiving daily prednisolone. The longest steroid-free interval for the nine children who were taken off steroids was a median (range) of 28.5 (0.1–54) months. Seven of the 15 children (47%) had relapses during attempted steroid-taper, of whom six had steroid-responsive relapses. One child, with FSGS, did not go into remission despite daily prednisolone therapy and was taken off Tac. At last follow-up, of the 15 children, 13 were still receiving Tac. The two who were taken off Tac had frequent relapses and were transitioned to other regimens. Figure 2 depicts the outcomes in the children in the form of a flow-diagram.Fig. 2

Bottom Line: There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings.In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS.Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California Davis Children's Hospital, 2516 Stockton Boulevard, Sacramento, CA 95817, USA. Lavjay.butani@ucdmc.ucdavis.edu

ABSTRACT
Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-beta immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-beta tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels.

Show MeSH
Related in: MedlinePlus