CLINICAL CORRELATIONS OF CYCLOSPORINE-SPECIFIC AND CYCLOSPORINE-NONSPECIFIC ASSAYS IN STABLE RENAL-TRANSPLANTS, ACUTE REJECTION, AND CYCLOSPORINE NEPHROTOXICITY

Accurate and early diagnosis of the cause of renal transplant dysfunct ion is important in successful patient management. Controversy exists as to whether a cyclosporine-specific or -nonspecific method is more p redictive of clinical events. In an attempt to answer this question, a ll episodes of acute renal dysfunction were reviewed in 322 stable ren al transplant recipients over a 20-month period. To diagnose the cause of each episode of renal dysfunction, an analysis was made of patient demographics; weight; serum creatinine; cyclosporine dose; cyclospori ne level, using a specific method-high-performance liquid chromatograp hy (HPLC)-and a nonspecific method fluorescent polarization immunoassa y (FPIA); changes in cyclosporine dose; renal biopsy; and response to any therapeutic intervention. There were 138 patients, who developed 2 79 episodes of renal dysfunction. Causes of renal dysfunction were cyc losporine-related (n = 103), acute rejection (n = 63), extracellular f luid volume depletion (n = 27), other (n = 59), and unknown (n = 27). The mean HPLC cyclosporine level was significantly different in patien ts with acute cyclosporine toxicity (p < 0.001) and patients with acut e rejection (p < 0.001) when compared to those with stable renal funct ion; the mean FPIA cyclosporine levels were not significantly differen t between the three groups. However, a larger percentage of patients w ith rejection were subtherapeutic when measured by HPLC, while a highe r proportion of patients with nephrotoxicity were above the therapeuti c range measured by FPIA. These results indicate that parent cyclospor ine is most important for immunosuppressive activity and suggests that cyclosporine metabolites may play a role in toxicity.