Ulinski Tim, Dubourg Laurence, Saïd Marie Hélène, Parchoux Bernadette, Ranchin Bruno, Cochat Pierre
Department of Pediatrics, Nephrology Unit, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France.
Pediatr Nephrol. 2005 Apr;20(4):482-5. doi: 10.1007/s00467-004-1778-4. Epub 2005 Feb 18.
Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3-15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C(IN)). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m(2) twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9+/-4.8 to 119.9+/-5.9 mL/1.73 m(2) per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26-2.94] mg/kg/d pre-MMF to 0.29 [0-1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.
肾毒性是环孢素A(CyA)治疗依赖类固醇(SD)和抵抗类固醇(SR)的儿童肾病综合征(NS)时众所周知的不良反应。我们分析了9名患有SD或SR NS的儿童(年龄:3.3 - 15.7岁,2名女孩),这些儿童在接受CyA治疗期间,通过菊粉清除率(C(IN))测量显示其肾小球滤过率(GFR)显著下降。逐渐引入霉酚酸酯(MMF),直至达到每日两次、剂量为1 g/1.73 m²的水平。引入MMF后停止CyA治疗,并尽可能减少口服类固醇剂量。中位随访261天后,我们的患者未出现MMF的不良反应,如腹泻或血液学异常。从CyA转换为MMF后,患有SD NS的儿童仍处于缓解期,无蛋白尿,而患有SR NS的儿童其残余蛋白尿无任何显著变化。在分析的任何儿童中,血清蛋白水平均无显著变化。GFR从平均76.9±4.8增加至119.9±5.9 mL/1.73 m²每分钟(P<0.001)。口服类固醇治疗可从MMF治疗前泼尼松剂量的中位数[范围]0.85[0.26 - 2.94]mg/kg/天降至0.29[0 - 1.1]mg/kg/天(P = 0.026),停用CyA后血压适度下降,但差异未达到统计学显著性。我们得出结论,至少在短期内,从CyA转换为MMF对于患有SDNS和SRNS的儿童在副作用以及疾病控制方面似乎是安全的。停止CyA治疗可使这些儿童的肾功能迅速改善,通常伴有类固醇减量,这可能对生长速度、血压和外貌带来额外益处。