ESPN 50th Annual Meeting

ESPN 2017


 
Surveillance biopsies of tacrolimus effect in childhood nephrotic syndrome
CHARLES PICKLES 1 ANDREW HARRIS 1 DENISE CHISHOLM 1 BEN REYNOLDS 1 SALLY JOHNSON 1 MORDI MUORAH 1 MILOS OGNJANOVIC 1 KATRINA WOOD 1 YINCENT TSE 1

1- GREAT NORTH CHILDRENS HOSPITAL, Newcastle
 
Introduction:

Tacrolimus is increasingly advocated as a steroid sparing agent in the management of nephrotic syndrome. As concerns exist about long term nephrotoxicity, interval renal biopsies have been advocated to detect early changes. Associations between histological changes and patient factors are not well established.

 

Material and methods:

Single centre review of surveillance renal histology of children who received tacrolimus to treat nephrotic syndrome between 2002 - 2015. For consistency a single histologist independently re-analysed all histology.

 

Results:

26 children (16 male, 1 non-caucasian, 25 minimal change, 1 FSGS) commenced tacrolimus at median age 4.9 years (range 1.4 - 8.9). 7/26 (27%) of first biopsy taken after median duration 4.7 years (range 1.9 to 6.9) demonstrated features of calcineurin inhibitor (CNI) nephrotoxicity. Toxicity was associated with higher mean 12-hour trough serum tacrolimus levels: 0/11 showed toxicity with levels o 4.36 to 5.54 µg/L vs. 7/15 (47%) with levels 5.69 to 7.36 µg/L (p <0.0001). No association was found with number of relapses, gender or duration of time on tacrolimus. Nephrotoxicity was mainly globally sclerosis or minimal chronic tubular changes.

 

10/19 patients without initial CNI toxicity underwent second biopsy at a median time of 5.0 (range, 1.8 – 6.7) years later. One developed toxicity. Estimated glomerular filtration rate in those who developed toxicity was normal. We attempted tacrolimus weaning in 20 patients: 11 patients relapsed, 4 within 2 months, further 5 within 1 year after dose reduction.

 

Conclusions:

Significant number of children on tacrolimus showed histological nephrotoxicity after a short duration of therapy. In this small single centre experience, toxicity correlated with tacrolimus level rather than duration. A high number relapsed shortly following dose reduction. We suggest maintaining tacrolimus levels ≤5.5 µg/L to minimise nephrotoxicity.