Sumethkul V, Changsirikulchai S, Lothuvachai T, Chalermsanyakorn P
Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Transplant Proc. 2006 Dec;38(10):3470-2. doi: 10.1016/j.transproceed.2006.10.097.
Optimal treatment for patients with chronic allograft nephropathy (CAN) is not known. Early intervention is preferred. We examined the benefit of adding sirolimus (SRL; C(0) 5-12 ng/mL: HPLC) on the rate of progression of early CAN. We identified patients with biopsy-confirmed Banff grade 1 CAN. After biopsy, patients were switched to SRL + CsA + prednisolone (SRL), MMF + CsA + prednisolone (MMF), or CsA + AZA + prednisolone (AZA). GFR was estimated by Cockcroft-Gault and MDRD formulae. The rate of GFR decline (delta GFR) was determined by calculating the slope of the regression line of estimated GFR (MDRD and Cockcroft-Gault method) at different times. Statistical analysis was performed by the Wilcoxon test. The 41 patients with CAN grade 1 were assigned to SRL: MMF: AZA = 12: 20: 9. Before biopsy; the graft age for SRL: MMF: AZA were 56 +/- 27: 70 +/- 48: 51 +/- 36 months; and the GFR (MDRD method), 38 +/- 8: 42 +/- 15: 36 +/- 14 mL/min; GFR (C-G method) 45 +/- 13, 42 +/- 12, 41 +/- 15 mL/min; trough CsA levels 152 +/- 36: 145 +/- 46: 177 +/- 61 ng/dL; delta GFR (MDRD method) -0.18 +/- 0.20: -0.15 +/- 0.59: -0.20 +/- 1.08; delta GFR (C-G method) -0.13 +/- 0.37: -0.19 +/- 0.24: -0.65 +/- 0.99. Follow-up time for SRL: MMF: AZA was 19 +/- 4: 35 +/- 32: 59 +/- 54 months. At last follow-up; GFR (MDRD method) for SRL: MMF: AZA were 39 +/- 13: 35 +/- 21: 40 +/- 24 mL/min; GFR (C-G method) 46 +/- 17, 37 +/- 18, 46 +/- 25 mL/min; BP 128 +/- 11/79 +/- 7: 131 +/- 22/80 +/- 14: 132 +/- 20/82 +/- 11 mm Hg; and CsA level 52 +/- 25: 122 +/- 41: 155 +/- 49. After biopsy, statin was prescribed in nine SRL, 10 MMF, and three AZA. ACEI was prescribed in two SRL, three MMF, and two AZA. Compared with the prebiopsy values, the delta GFR (MDRD method) changed to -0.04 +/- 0.31 (SRL; P = .04), -0.17 +/- 0.40 (MMF; P = .60), and -0.97 +/- 1.52 (AZA: P = .16). Delta GFR (C-G method) was also significantly improved in the SRL group (-0.02 +/- 0.47; P = .05) but not in the MMF (-0.13 +/- 0.51; P = .53) or AZA (-0.54 +/- 1.78; P = .44). We concluded that patients with early CAN who are switched to SRL and low-dose CsA have a significant attenuation of the rate of GFR declination when compared with patients who receive MMF or AZA addition.
慢性移植肾肾病（CAN）患者的最佳治疗方案尚不清楚。早期干预更为可取。我们研究了添加西罗莫司（SRL；血药浓度谷值5 - 12 ng/mL：高效液相色谱法）对早期CAN进展速度的影响。我们纳入了经活检确诊为Banff 1级CAN的患者。活检后，患者被分为接受SRL + 环孢素A（CsA）+ 泼尼松龙（SRL组）、霉酚酸酯（MMF）+ CsA + 泼尼松龙（MMF组）或CsA + 硫唑嘌呤（AZA）+ 泼尼松龙（AZA组）治疗。采用Cockcroft - Gault公式和MDRD公式估算肾小球滤过率（GFR）。通过计算不同时间点估算GFR（MDRD和Cockcroft - Gault法）回归线的斜率来确定GFR下降速率（ΔGFR）。采用Wilcoxon检验进行统计分析。41例1级CAN患者被分配至SRL组：MMF组：AZA组 = 12：20：9。活检前，SRL组、MMF组、AZA组的移植肾龄分别为56±27个月、70±48个月、51±36个月；GFR（MDRD法）分别为38±8 mL/min、42±15 mL/min、36±14 mL/min；GFR（C - G法）分别为45±13 mL/min、42±12 mL/min、41±15 mL/min；CsA谷值水平分别为152±36 ng/dL、145±46 ng/dL、177±61 ng/dL；ΔGFR（MDRD法）分别为 - 0.18±0.20、 - 0.15±0.59、 - 0.20±1.08；ΔGFR（C - G法）分别为 - 0.13±0.37、 - 0.19±0.24、 - 0.65±0.99。SRL组、MMF组、AZA组的随访时间分别为19±4个月、35±32个月、59±54个月。在最后一次随访时，SRL组、MMF组、AZA组的GFR（MDRD法）分别为39±13 mL/min、35±21 mL/min、40±24 mL/min；GFR（C - G法）分别为46±17 mL/min、37±18 mL/min、46±25 mL/min；血压分别为128±11/79±7 mmHg、131±22/80±14 mmHg、132±20/82±11 mmHg；CsA水平分别为52±25 ng/dL、122±41 ng/dL、155±49 ng/dL。活检后，9例SRL组患者、10例MMF组患者和3例AZA组患者使用了他汀类药物。2例SRL组患者、3例MMF组患者和2例AZA组患者使用了血管紧张素转换酶抑制剂（ACEI）。与活检前的值相比，ΔGFR（MDRD法）在SRL组变为 - 0.04±0.31（P = 0.04），在MMF组变为 - 0.17±0.40（P = 0.60），在AZA组变为 - 0.97±1.52（P = 0.16）。SRL组的ΔGFR（C - G法）也显著改善（ - 0.02±0.47；P = 0.05），而MMF组（ - 0.13±0.51；P = 0.53）和AZA组（ - 0.54±1.78；P = 0.44）未改善。我们得出结论，与接受MMF或AZA治疗的患者相比，改用SRL和低剂量CsA治疗的早期CAN患者GFR下降速率显著减缓。
