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Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use.
Kelly D Smith1, Lucile E Wrenshall, Roberto F Nicosia
1Department of Pathology, University of Washington Medical Center, Seattle, Washington , USA.
Journal of the American Society of Nephrology : JASN
|March 28, 2003
Summary
Rapamycin use increases the risk of delayed graft function (DGF) in kidney transplant recipients. This immunosuppression may cause tubular injury and unique cast nephropathy, suggesting potential toxicity.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Delayed graft function (DGF) affects 15-25% of cadaveric and up to 9% of living donor kidney transplants.
- Immunosuppression choice is a potential factor influencing DGF development.
Purpose of the Study:
- To investigate the impact of immunosuppression, specifically rapamycin, on the incidence and characteristics of DGF in kidney transplant recipients.
Main Methods:
- Retrospective analysis of 144 first kidney allograft recipients transplanted between November 1999 and September 2001.
- Comparison of donor, recipient, procedural factors, and biopsy results between patients with and without DGF.
- Histologic, immunohistochemical, and ultrastructural examination of biopsies from patients with DGF.
Main Results:
- DGF occurred more frequently in patients treated with rapamycin (25%) compared to those without (8.9%) (P=0.02).
- Rapamycin dose positively correlated with DGF incidence (P=0.008).
- Biopsies in DGF patients showed acute tubular injury; 12 patients on rapamycin and tacrolimus developed intratubular cast formation composed of degenerating tubular cells.
Conclusions:
- Rapamycin therapy may increase tubular epithelial cell toxicity or retard healing, leading to a higher incidence of DGF.
- Combined rapamycin and calcineurin inhibitor treatment may cause significant tubular injury and a unique cast nephropathy.