他克莫司延缓移植性肾病进展的临床观察

Eeffects of switching cyclosporine A to tacrolimus on chronic allograft nephropathy after kidney transplantation

目的:观察他克莫司(FK506)与霉酚酸酯(MMF)联合应用延缓移植性肾病肾功能进展的疗效。方法:选择肾移植术后肾功能异常,并经移植肾活检病理证实为慢性移植性肾病患者46例,将原环孢素A(CsA)切换为FK506,同时联合MMF和激素。FK506起始剂量0·08mg/(kg·d),MMF1.5g/d,监测切换12个月后血清肌酐、肾小球滤过率(GFR)[ml/(min·1·73m2)]、24h尿蛋白定量(g)变化。结果:切换为FK506治疗12个月后,平均血清肌酐由(293±45)μmol/L降至(198±24)μmol/L(P<0·05)。GFR由(39·77±2·35)ml/(min·1·73m2)提高至(49·87±3·17)ml/(min·1·73m2),24h尿蛋白定量由(4·8±0·8)g降至(1·9±0·7)g(P<0·05)。副作用包括高血糖(6例)、震颤(8例)、腹泻(4例)、白细胞减少(2例)、带状疱疹(1例)、骨痛(1例)。结论:FK506可以有效延缓移植肾病进展。

Objective： Chronic nephrotoxicity is the major adverse effect of long-term cyclosporine A （CsA） therapy and is characterize by striped interstitial fibrosis, tubular atrophy, afferent arteriolar hyalinosis, and interstitial mononuclear cellular infiltration. The aims of this paper are to study the feasibility and safety of tacrolimus and mycophenolate moftetil delaying the course of the grafted renal function failure. Methodology：Forty-six renal transplantation patients with grafted renal dysfunction and chronic allograft nephropathy proved by pathological examinations were collected in this study. A cyclosporine based regimen was converted to a tacrolimus-based regimen. The initial dose of tacrolimus was 0. 08 mg/（ kg · d） . The initial dose of MMF was 1 500 mg/d. The levels of serum creatinine, GFR（ mL/min· 1.73 m^2 ） and 24- hours urine protein excretion were monitored before and after 12 months of switching CsA to tacrolimus in those patients. Results：The level of serum creatinine （μmoL/L） were decreased from （293 ± 45 ） to （ 198 ± 24）, GFR （ mL/min· 1.73 m^2） were increased from （ 39. 77 ± 2. 35 ） to （49. 87 ± 3. 17） , and 24-hour urine protein excretion （g） were dropped down from （4. 8 ± 0. 8） to （ 1.9 ±0. 7） （ P 〈 0. 05 ） before and after 6 months of switching CsA to tacrolimus. The side effects of this immunosuppressive regimen included hyperglycemia （ 6 cases）, tremor （ 8 cases）, diarrhea （ 4 cases）, neutropenia （ 2 cases）, herpes zoster （ one case）, and pain on the bone （ one case）. Conclusion： Switching CsA based regimen to tacrolimus based regimen was an effective and safe alternative therapy for delaying the course of renal function induced by chronic allograft nephropathy after kidney transplantation.