Renal transplantation is considered a cost-effective treatment compared to dialysis and represents a significant percentage of public health resources. Post-transplant treatment requires the use of three immunosuppressive drugs. The immunosuppressive regimens consists of a corticosteroid, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antiproliferative agent (azathioprine or mycophenolate) and also by sirolimus or everolimus. In Brazil, the Unified Health System (as known as Sistema Único de Saúde - SUS) is responsible for 95 percent of all kidney transplants performed, as well as ensuring access to immunosuppressive drugs. Therefore, there is a huge and growing economic impact caused by the distribution of these drugs in SUS. We evaluated the factors associated with kidney graft loss in patients who received deceased donor organ and used maintenance immunosuppressive regimens in SUS, in fifteen years.
We analyzed a nationwide cohort of kidney transplant recipients from January 2000 to December 2015 developed through deterministic-probabilistic linkage of SUS administrative databases: Hospital Information System (SIH/SUS); Subsystem for High Complexity Procedures (SIA/SUS) and the Mortality Information System (SIM). Graft loss was defined as death or dialysis for more than three months. All regimens included corticosteroid. We used Cox proportional hazards model to evaluate the factors associated with progression to graft loss.
In total, 18,333 patients were included; 58.5 percent used tracolimus+mycophenolate, 11.7 percent cyclosporine+mycophenolate, 8.9 percent tacrolimus+azathyoprine, 5.5 percent cyclosporine+azathyoprine and 15.4 percent received other immunosuppressive regimens (sirolimus+mycophenolate, everolimus+mycophenolate, tacrolimus, mycophenolate, cyclosporine, azathyoprine) . Most patients were male with a median age of 46 years. A higher risk of graft loss was associated with the use of tracolimus+mycophenolate (HR = 1.069; 95% CI, 0.999–1.146), sirolimus+mycophenolate (HR1.395;95% CI, 1 .150–1.692), tracolimus (monotherapy) (1.468;1.239–1.739); mycophenolate (monotherapy) (1.297;1.126–1.493), male gender (1.144; 1.072–1.221), an additional year of age (1.010; 1.007–1.013), a median dialysis period greater than 38 months (1.266; 1.182–1.356), a diagnosis of diabetes (1.211; 1.071–1.367) and a diagnosis of arterial hypertension (1.209; 1.134–1.288) (HR=1.468;95% CI,1.239 −1.739); mycophenolate (monotherapy) (HR = 1.297; 95% CI, 1.126–1.493), male gender (HR = 1.144; 95% CI 1.072–1.221), an additional year of age (HR = 1.010; 95% CI, 1.007–1.013), a median dialysis period greater than 38 months (HR = 1.266; 95% CI, 1.182–1.356), a diagnosis of diabetes (HR = 1.211; 95% CI, 1.071–1.367) and a diagnosis of arterial hypertension (HR = 1.209; 95% CI, 1.134–1.288)as the primary cause of chronic kidney disease.
In Brazil, the use of regimens mycophenolate, tacrolimus, tacrolimus+mycophenolate was associated a higher risk of graft loss, among other factors. The choice of drug therapy is one of the few factors that influence survival amenable to direct action by health professionals. Therefore, the results of this study are important and should be disseminated aiming to better outcomes for kidney transplant patients.