Ahlenstiel Thurid, Offner Gisela, Strehlau Jürgen, Pape Lars, Froede Kerstin, Ehrich Jochen H H, Schwarz Anke, Heuft Hans-Gert, Klempnauer Jürgen
Department of Pediatric Kidney, Liver and Metabolic Diseases, Medical School Hannover, Hannover, Germany.
Xenotransplantation. 2006 Mar;13(2):141-7. doi: 10.1111/j.1399-3089.2006.00279.x.
Antigen-specific immunoadsorption combined with rituximab offers the possibility for ABO-incompatible kidney transplantation without splenectomy.
An 8-year-old mentally retarded girl with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis due to mitochondriopathy poorly tolerated hemodialysis. Paternal blood group A1B was incompatible with blood group B of the child. Therefore, we decided to perform the first ABO-incompatible renal transplantation in a child in Germany using antigen-specific immunoadsorption. Rituximab (1 x 375 mg/m2) was administered 2 weeks before the first immunoadsorption (Glycosorb) ABO A-column). Triple-drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) was simultaneously started with immunoadsorption. Initial tacrolimus levels were targeted between 15 and 20 ng/ml. Before transplantation, six immunoadsorptions were applied on days -9, -7, -4, -3, -2 and -1. Intravenous immunoglobulin (0.5 g/kg) was administered preoperatively. After transplantation, three immunoadsorptions were performed on days +4, +6 and +8.
Before transplantation, antibody (Ab) titers against paternal erythrocytes (20 degrees C) were reduced from 1 : 64 to 1 : 4 by six antigen-specific immunoadsorptions. After transplantation, we performed three more immunoadsorptions and the Ab titers were stable between 1 : 1 and 1 : 8. One, 2 and 8 months later we observed increases in the Ab titer up to 1 : 32 requiring no change in immunosuppressive therapy. No side effects of immunoadsorption were observed. The girl had excellent initial graft function with a serum creatinine of 55 to 70 micromol/l. Two weeks after transplantation, graft biopsy showed no signs of rejection; there was focal positivity for C4d only. Twelve months after transplantation, renal function was stable, with a serum creatinine of 117 micromol/l. Episodes of rejection or severe infections were absent.
ABO-incompatible transplantation using antigen-specific immunoadsorption and rituximab may serve as a suitable alternative for children urgently needing renal transplantation and missing a blood group-compatible donor.
抗原特异性免疫吸附联合利妥昔单抗为非 ABO 血型相合肾移植且无需脾切除术提供了可能。
一名 8 岁智力发育迟缓女孩,患有类固醇抵抗型肾病综合征及因线粒体病导致的局灶节段性肾小球硬化,难以耐受血液透析。父亲血型为 A1B,与孩子的 B 型血不相合。因此,我们决定在德国为一名儿童进行首例使用抗原特异性免疫吸附的 ABO 血型不相合肾移植。在首次免疫吸附(Glycosorb ABO A 柱)前 2 周给予利妥昔单抗(1×375mg/m²)。在进行免疫吸附的同时开始三联药物免疫抑制治疗(他克莫司、霉酚酸酯和泼尼松龙)。初始他克莫司血药浓度目标值为 15 至 20ng/ml。移植前,在第 -9、-7、-4、-3、-2 和 -1 天进行了 6 次免疫吸附。术前给予静脉注射免疫球蛋白(0.5g/kg)。移植后,在第 +4、+6 和 +8 天进行了 3 次免疫吸附。
移植前,通过 6 次抗原特异性免疫吸附,针对父亲红细胞(20℃)的抗体(Ab)滴度从 1:64 降至 1:4。移植后,我们又进行了 3 次免疫吸附,Ab 滴度稳定在 1:1 至 1:8 之间。1 个月、2 个月和 8 个月后,我们观察到 Ab 滴度升高至 1:32,但无需改变免疫抑制治疗方案。未观察到免疫吸附的副作用。女孩移植初期肾功能良好,血清肌酐为 55 至 70μmol/l。移植后 2 周,移植肾活检未显示排斥反应迹象;仅 C4d 呈局灶阳性。移植后 12 个月,肾功能稳定,血清肌酐为 117μmol/l。未发生排斥反应或严重感染事件。
使用抗原特异性免疫吸附和利妥昔单抗的 ABO 血型不相合移植可能是急需肾移植但缺少血型相合供体的儿童的合适替代方案。