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Variability in tacrolimus blood levels increases the risk of late rejection and graft loss after solid organ transplantation in older children
Author(s) -
PollockBarZiv Stacey M.,
Finkelstein Yaron,
Manlhiot Cedric,
Dipchand Anne I.,
Hebert Diane,
Ng Vicky L.,
Solomon Melinda,
McCrindle Brian W.,
Grant David
Publication year - 2010
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2010.01409.x
Subject(s) - tacrolimus , medicine , immunosuppression , hazard ratio , transplantation , organ transplantation , risk factor , kidney , liver transplantation , kidney transplantation , urology , surgery , gastroenterology , confidence interval
Pollock‐BarZiv SM, Finkelstein Y, Manlhiot C, Dipchand AI, Hebert D, Ng VL, Solomon M, McCrindle BW, Grant D. Variability in tacrolimus blood levels increases the risk of late rejection and graft loss after solid organ transplantation in older children.
Pediatr Transplantation 2010: 14:968–975. © 2010 John Wiley & Sons A/S. Abstract: Late graft rejection impairs the long‐term function of organ transplants in children. Previous studies suggest patients with wide variation in tacrolimus levels may have higher rates of late kidney and liver graft rejection. The reproducibility of this finding and impact on graft and recipient survival have not been reported. We investigated factors associated with late rejection >6 months post‐transplant in 144 heart, kidney, liver, and lung transplant recipients (ages 8–18, ≥1‐yr survivors, receiving tacrolimus‐based immunosuppression), comparing late rejectors (n = 61, 42%) to non‐rejectors (no rejection >6 months); groups had similar mean tacrolimus concentrations ≤6 months post‐transplant. For all organ types, increased standard deviation in intrapatient tacrolimus blood levels was an independent risk factor for late rejection (OR 1.6 [CI 1.1–2.1]; p = 0.02). Each 1‐point increase in s.d. > 2 of tacrolimus level >6 months post‐transplant associated with 1.58 increase in hazard of graft loss (p = 0.003). Graft survival (conditional on one‐yr survival) was significantly better for those with s.d. < 2 at >6 months post‐transplant: 98% at three and five yr, versus 88%, 70%, at three and five yr, in patients with s.d. > 2 (p = 0.003). In conclusion, high s.d. in serial tacrolimus concentrations associated with increased risk of late rejection and graft loss in pediatric organ transplant recipients, providing opportunities for screening and interventions.