Table 2.

Clinical risk factors for the development of calcineurin inhibitor nephrotoxicity

Risk Factors for Calcineurin Inhibitor Nephrotoxicity
Systemic overexposure to cyclosporine and tacrolimus
Local exposure to cyclosporine and tacrolimus
    interactions with drugs interfering with ABCB1-mediated transport in the tubular epithelial cells (e.g., mTOR inhibitors)
    ABCB1 genotype of the kidney
    ABCB1 expression in renal tubular epithelial cells
Exposure to metabolites of cyclosporine and tacrolimus
    CYP3A4/5 genotype of the patient
    CYP3A5 expression in renal tubular epithelial cells
    interactions with other drugs which lead to altered exposure to calcineurin inhibitor metabolites (e.g. ketoconazole)
Older kidney age
Use of nonsteroidal anti-inflammatory drugs
Salt depletion and diuretic use
Genetic polymorphisms of other genes (e.g., TGF-β, ACE)
  • ABCB1, ATP-binding cassette subfamily B, member 1; TGF-β, transforming growth factor β; ACE, angiotensin converting enzyme.