Sarwal M M, Cecka J M, Millan M T, Salvatierra O
Department of Surgery, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Transplantation. 2000 Dec 27;70(12):1728-36. doi: 10.1097/00007890-200012270-00012.
Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups.
Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.
终末期肾病婴儿在接受肾移植的任何亚组中,早期移植物丢失和死亡风险最高。本研究评估供体组织量和急性肾小管坏死(ATN)对活体供体(LD)和尸体供体(CAD)成人尺寸肾脏(ASK)、小儿CAD肾脏以及肝肾联合移植的婴儿和小儿受者的移植物存活及急性排斥反应发生率的影响。方法:分析了单中心的婴儿和小儿肾移植以及向器官共享联合网络(UNOS)科学肾脏移植登记处报告的病例。在斯坦福大学,对45例连续的体重≤15 kg、平均体重11.2±2.6 kg的肾移植受者进行了多变量分析。将UNOS登记处0 - 2.5岁(n = 548)和2.5 - 5岁(n = 743)年龄组的结果与6 - 12岁、13 - 18岁以及风险最低的19 - 45岁成人组进行比较。斯坦福大学研究结果:2年时移植物存活率为97.8±0.0%,8年时为84.6±0.1%。活检证实的排斥反应发生率在最初3个月为8.8%,8年随访期间为15.5%。小儿CAD肾脏均无ATN。排斥反应仅局限于小儿CAD肾脏(3/3),小儿CAD肝肾联合移植中无肾脏排斥反应(0/6;P = 0.003)。4例ASK移植发生ATN(1例术后发生,3例晚期发生),且均易发生随后的急性排斥反应(4/4),而无ATN的ASK移植无排斥反应(0/32;P < 0.001)。移植后3年,发生ATN的ASK的平均血清肌酐水平更差(1.5 vs. 0.9 mg/dL;P < 0.001),且所有发生排斥反应的移植物的平均血清肌酐水平也更差(1.2 vs. 0.9 mg/dL;P < 0.05)。UNOS研究结果:在研究的5个年龄组中,在两个最年幼年龄组接受无ATN的ASK移植的受者中观察到显著更好(P < 0.001)的长期移植物存活率:移植后6年,0 - 2.5岁和2.5 - 5岁年龄组中LD受者分别为82±3%和81±3%,CAD受者分别为70±7%和78±4%。此外,在无ATN的LD组中,第1年后预计的移植物半衰期至少与19 - 45岁的HLA相同同胞受者相当:0 - 2.5岁和2.5 - 5岁年龄组分别为26.3±5年和29.3±6年以及HLA相同移植为23.3±1年。0 - 2.5岁和2.五岁无ATN的CAD受者的移植物半衰期与19 - 45岁无ATN的LD移植受者相当或更好:分别为15.4±7年和23.7±8年,而LD移植为15.0±0.3年。与年长年龄组相比,两个较年幼受者年龄组的平均血清肌酐水平更好。
在无ATN的情况下,ASK或肝肾联合移植的供体组织量增加似乎对这些同种异体移植物的婴儿和小儿受者具有保护作用。这在单中心经验中表现为无排斥反应状态延长,在UNOS分析中表现为移植物存活和功能增强,与LD婴儿和小儿受者的HLA相同同胞移植以及CAD婴儿和小儿受者的LD成人结果相当。为通过任何机制优化这种保护作用,ASK或肝肾联合移植的婴儿受者绝对避免ATN至关重要。