RESUMO
Patients with high tacrolimus clearance are more likely to experience transient under-immunosuppression in case of a missed or delayed dose. We wanted to investigate the association between estimated tacrolimus clearance and development of graft interstitial fibrosis and tubular atrophy (IFTA) in kidney transplant recipients. Associations between estimated tacrolimus clearance [daily tacrolimus dose (mg)/trough concentration (µg/l)] and changes in IFTA biopsy scores from week 7 to 1-year post-transplantation were investigated. Data from 504 patients transplanted between 2009 and 2013 with paired protocol biopsies (7 weeks + 1-year post-transplant) were included. There were no differences in baseline biopsy scores (7 weeks) in patients with different estimated tacrolimus clearance. Increasing tacrolimus clearance was significantly associated with increased ci + ct score of ≥2 at 1 year, odds ratio of 1.67 (95% CI; 1.11-2.51). In patients without fibrosis (ci + ct ≤ 1) at 7 weeks (n = 233), increasing tacrolimus clearance was associated with development of de novo IFTA (i + t ≤ 1 and ci + ct ≥ 2) at 1 year, odds ratio of 2.01 (95% CI; 1.18-3.50) after adjusting for confounders. High tacrolimus clearance was significantly associated with development of IFTA the first year following renal transplantation.
Assuntos
Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Túbulos Renais/patologia , Rim/patologia , Tacrolimo/farmacocinética , Adulto , Idoso , Atrofia , Citocromo P-450 CYP3A/fisiologia , Feminino , Fibrose , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Few published reports have examined the incidence and outcomes for patients with carcinoid lung tumors. The aim of the current study was to explore incidence, type of surgical treatment given, and outcome for patients with typical (TC) and atypical (AC) lung carcinoids in a national cohort (Norway). METHODS: All lung-cancer patients diagnosed in the period 1993-2005 and who were reported to the Cancer Registry of Norway were identified. Biopsies or resection specimens were reviewed and reclassified according to the World Health Organization (WHO) 2004 classification. Surgically treated patients were staged according to the seventh edition of the pathological tumor-node-metastasis (pTNM) staging system. RESULTS: Of 26665 lung cancers registered during the period, 265 (1%) had carcinoid tumors, of which 11 were diagnosed coincidentally at autopsy. In the remaining 254 patients, TCs were found in 188 cases, and ACs were found in 59 cases; seven cases had unclassifiable carcinoids. Of the 217 resected tumors, 173 (80%) were TCs. General surgeons performed 94 resections, including 11 of 17 pneumonectomies. All six bronchial resections were performed by thoracic surgeons. Of the 33 operated patients who died during follow-up, 18 had metastatic carcinoid tumors, of which 10 (56%) were ACs. In 37 non-resected patients (15 with AC and seven with unclassifiable histology), metastatic or locally advanced disease (N=21, 12 of which were ACs) was the main cause of inoperability and death. Five-year survival for all patients was 92% for TC and 66% for AC; for resected patients, the survival rates were 96% and 79%, respectively. CONCLUSIONS: Carcinoids are rare malignant tumors and are, in most cases, resectable; the TC subgroup had better prognosis than the AC in univariate analyses. The main cause of death was metastasis/locally advanced tumor at presentation or recurrent disease following resection; both situations were three times more common in patients with AC.