【摘要】 目的 觀察激素加霉酚酸酯（mycophenolate mofetil，MMF）和他克莫司（tacrolimus，FK506）的多靶點方案治療難治性腎小球疾病的療效及安全性。 方法 2008年5月-2010年3月收治的15例狼瘡性腎炎（lupus nephritis，LN）、3例膜增生性腎小球腎炎（membranoproliferative glomerulonephritis，MPGN）及3例膜性腎病（membranous nephropathy，MN）患者，因多種免疫抑制劑治療無效或復發而改用多靶點療法。潑尼松以30~40 mg/d起始，逐漸減量。MMF 和FK506起始劑量分別為0.5 g/d或1 mg/d，目標血藥濃度分別為20~40 mg/（h·L）或5~8 ng/mL。定期隨訪觀察肝腎功能、尿蛋白定量、不良反應等指標。 結果 治療6個月時15例LN中7例（46.7%）完全緩解（complete remission，CR），5例（33.3%）部分緩解（partial remission，PR），3例（20%）無效（no response，NR）。3例MPGN均表現為NR。3例MN中2例（66.7%）PR，1例（33.3%）NR。治療過程中呼吸道感染及脫發各1例，胃腸不適2例，肌酐逐步升高3例，無死亡或退出者。 結論 多靶點療法對難治性LN安全、有效，可作為其他免疫抑制劑治療無效或復發時的選擇方案，但對MPGN和MN療效欠佳，需進一步研究。【Abstract】 Objective To investigate the efficacy and safety of multitarget therapy with steroid, mycophenolate mofetil (MMF) and tacrolimus (FK506) in the treatment of refractory glomerular diseases. Methods Fifteen patients with lupus nephritis (LN), 3 patients with membranoproliferative glomerulonephritis (MPGN) and 3 patients with membranous nephropathy (MN) who failed the previous immunosuppressive therapy from May 2008 to March 2010 in our hospital were treated with multitarget therapy. The initial dose of prednisone was 30-40 mg/d and then tapered gradually. MMF and FK506 were started at 0.5 g/d or 1 mg/d, and the target blood concentration of the two drugs was 20-40 mg/(h·L) and 5-8 ng/mL respectively. Clinical parameters such as liver and renal function, urine protein, and side effects were recorded and analyzed in the regular follow-up. Results After 6 months of treatment, 7 (46.7%) of the 15 LN patients achieved complete remission (CR), 5 (33.3%) achieved partial remission (PR), while 3 (20%) failed this treatment and had no response (NR). All of the three MPGN patents had NR to this combined therapy. Two (66.7%) of the 3 MN patents achieved PR while 1 (33.3%) had NR. No patient withdrew or died because of side effects. One patient developed upper respiratory infection, one experienced alopecia, two developed gastrointestinal syndrome and three experienced gradual increasing in the serum creatinine. Conclusion Multitarget therapy with FK506, MMF and steroid is an effective and safe therapy for refractory lupus nephritis and it can be used in patients who are resistant to the conventional immunosuppressive therapy. However, this combined therapy does not meet a satisfactory result in patients with MN and MPGN, which entails further study.
Objective To investigate the prognostic value of troponin I ( cTNI) , brain natriuretic peptide ( BNP) and D-dimer in acute pulmonary embolism ( APE) .Methods The plasma levels of cTNI, BNP, and D-dimer were measured in 98 consecutive patients with APE at the time of admission. The relationship between these parameters and mortality were evaluated. Results APE was diagnosed in 98 consecutive patients during January 2009 to December 2010, in which 49 were males and 49 were females. 14 ( 14. 3% ) patients died at the end of follow-up. The patients with positive cTNI tests had more rapid heart rates, higher rate of syncope, cardiogenic shock and mortality than the patients with normal serumcTNI. However the age and blood pressure were lower in the patients with abnormal serum cTNI ( P lt; 0. 05) . A receiver-operating characteristic curve analysis identified BNP≥226. 5 ng/L was the best cut-off value ( AUC 0. 829, 95% CI 0. 715-0. 942) with the negative predictive value of 97. 1% for death. The mortality of the patients whose serum D-dimer level ranging from 500 to 2499 ng/mL, 2500 to 4999 ng/mL, and ≥5000 ng/mL was 7. 8% , 12% , and 41. 2% , respectively ( P = 0. 009) . Upon multivariate analysis, cardiogenic shock ( OR=2. 931, 95% CI 0. 828-12. 521, P =0.000) , cTNI≥0. 3 ng/mL ( OR=1. 441, 95% CI 0. 712-4. 098, P = 0. 0043) , BNP gt; 226. 5 ng/L ( OR = 1. 750, 95% CI 0. 690-6. 452, P = 0. 011) and D-dimer≥5000 ng/mL( OR = 1. 275, 95% CI 0. 762-2. 801, P = 0. 034) were independent predictors of death. Conclusions Combined monitoring of cTNI, BNP or D-dimer levels is helpful for prognosis prediction and treatment decision for APE patients.