Efficacy and safety outcomes among de novo renal transplant recipients managed by C2 monitoring of cyclosporine a microemulsion: results of a 12-month, randomized, multicenter study.

BACKGROUND: The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated, but C2 targets in renal transplant recipients during the first year require validation. METHODS: MO2ART was a prospective, multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C2 target ranges (months 4-6, 1,000-1,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12. RESULTS: A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C2, n=131; lower-C2, n=119). GFR at 12 months did not differ between the higher- and lower-C2 groups (65+/-17 mL/min vs. 66+/-14 mL/min). When patients were regrouped according to C2 achieved by months 8 to 12, those with the lowest C2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C2 group, n=2; lower-C2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months. CONCLUSION: Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.

Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion.

BACKGROUND: MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here. METHODS: MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 microg/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies. RESULTS: At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 micromol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 microg/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11). CONCLUSIONS: Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.

End-stage renal disease and its treatment in Latin America in the twenty-first century.

The Latin American Society of Nephrology and Arterial Hypertension's Dialysis and Transplant Registry was chartered in 1991. It collects information on ESRD and its treatment in 20 countries of the region. The prevalence of patients on renal replacement therapy (RRT) increased from 129 pmp in 1992 to 447 pmp in 2004; in 2004, 56% of the patients were on hemodialysis, 23% on peritoneal dialysis, and 21% had a functioning kidney graft. The highest rates of prevalence were reported in Puerto Rico (1027 pmp), Chile (686 pmp), and Uruguay (683 pmp). Hemodialysis was widely used, except in El Salvador, Mexico, Guatemala, Nicaragua, and the Dominican Republic, where peritoneal dialysis predominated. Incidence rate increased from 27.8 pmp to 147 pmp in the same period of observation; the lowest rate was reported in Guatemala (11.4 pmp) and the highest in Puerto Rico (337.4 pmp). Diabetes mellitus was the leading cause of renal failure in incident patients; the highest rates were reported in Puerto Rico (62.2%) and Mexico (60%). Forty-four percent of the incident population were older than 65 years. Access to renal replacement therapy was universal in Argentina, Brazil, Chile, Cuba, Puerto Rico, Uruguay, and Venezuela, while was restricted in other countries. Main causes of death in dialysis were cardiovascular (44%) and infectious disease (26%). The rate of renal transplantation increased from 3.7 pmp in 1987 to 14.5 in 2004; fifty-three percent of the organs came from cadavers. Overall, donation rate was 5.9 pmp. In conclusion, the prevalence and incidence rates have increased over the years, and diabetes mellitus has emerged as the leading cause of kidney disease in the region. Although the rate of kidney transplantation has increased, the number remains insufficient to match the growing demand. The implementation of renal health programs in the region is urgently needed.