Proteinuria as a useful clinical marker of cyclosporine nephrotoxicity in renal transplant patients

Abstract

A SIGNIFICANT improvement in the success of organ transplantation during the last 20 years has been observed mainly due to the introduction of drugs like cyclosporine (CyA). Although nephrotoxicity (NT) is the major dose-limiting adverse event for this drug, most of immunosuppressive regimens continue to depend on CyA. CyA trough blood levels must be monitored to ensure that the concentration of this drug remains within its narrow therapeutic range. However, it has been questioned because of its inability to adequately reflect systemic exposure in terms of area under the curve. Unfortunately, drug monitoring may not always detect or prevent NT. NT is difficult to distinguish from chronic allograft rejection, which is a particular problem in renal transplantation. Although morphologic criteria for the differential diagnosis between chronic rejection (CR) and CyA-associated NT have been proposed, the risk of biopsy is limiting. Early biopsies are strongly recommended for patients whose serum creatinine levels increase from baseline values. When biopsies are performed too late, after months or years of severe impairment of renal function, they offer little change to decipher the morphologic lesions. CR is frequently associated with development of proteinuria. Because tubulointerstitial damage is one of the most important adverse effects when CyA is administrated chronically, proteinuria should not be present. The aim of the study was to analyze whether the development of proteinuria could be a useful clinical hallmark to distinguish CR from CyA NT.