Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy-proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.
The role of multidrug resistance and P-glycoprotein (P-gp) in the development of drug-resistant tumor cells has been extensively studied. As more knowledge on the physiological functions of P-gp has accumulated, the effects of P-gp modulation on the pharmacokinetics and the pharmacodynamics of many drugs have become apparent. Solid organ transplant recipients receive numerous medications that are substrates for P-gp. The objective of this review is to discuss the effects of P-gp modulation on the pharmacokinetics and the pharmacodynamics of immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus, and corticosteroids. Pharmacokinetic alterations may occur in drug absorption since P-gp is in the small bowel, in drug distribution since P-gp functions in the blood-brain barrier, in drug metabolism since P-gp and cytochrome P450 3A have linked functions, and in drug elimination since P-gp is in the bile canaliculi and renal tubules. A link between P-gp and organ rejection has been speculated since upregulation of the P-gp pump may restrict immunosuppressant drug entry into immunocompetent cells. A further understanding of P-gp regulation upon chronic exposure to P-gp substrates and inhibitors and the potential administration of selective P-gp inhibitors will enhance our ability to use potent immunosuppressive drugs in organ transplant patients.
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