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Abstract
Objectives 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.
Methods Single centre review of surveillance renal histology of children who received tacrolimus to treat nephrotic syndrome between 2002–2015.
Duration on tacrolimus and nephrotoxicity.
Average trough 12 hours tacrolimus levels from starting tacrolimus to first biopsy. Toxicity associated with higher levels: 0/10 showed toxicity with levels of 4.36 to 5.54 μg/L vs. 9/15 (60%) with levels 5.69 to 7.36 μ/L (p < 0.0001)
Results 25 children (16 male, 1 non-caucasian, 21 minimal change, 4 FSGS) commenced tacrolimus at median age 4.0 years (range 1.4–8.9). 9/25(35%) 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 of 4.36 to 5.54 µg/L vs. 9/15 (60%) 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. Eight patients without initial CNI toxicity underwent second biopsy at a median time of 4.9 (range, 4.0–5.4) years later. Two 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 (See Figures 1 and 2).
Conclusion 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.