Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada.
Transplantation. 2010 Feb 15;89(3):334-40. doi: 10.1097/TP.0b013e3181bc5e49.
In pediatric recipients, the pathophysiology of chronic renal allograft injury is poorly understood.
We studied the evolution and determinants of tubulointerstitial, vascular, and glomerular injury in 240 pediatric protocol renal allograft biopsies during the first 5 years posttransplant.
Chronic tubulointerstitial injury (ci, ct) developed predominantly during the first 12 months posttransplant, whereas chronic vascular damage (cv, and arteriolar hyalinosis [ah]) and global glomerulosclerosis (gs) became increasingly prevalent at 25 to 36 months and beyond. Chronic interstitial lesions were associated with acute rejection and borderline histology (odds ratio [OR] 2.3, P<0.04), recipient body surface area less than 1.0 m2 (OR 3.6, P<0.05), and obesity (OR 2.0, P<0.03). Determinants of ct were acute rejection (OR 2.6, P=0.02) and acute tubular necrosis (OR 2.8, P<0.04). Vascular fibrous intimal thickening and ah were associated with donor hypertension (OR 3.6, P=0.001) and recipient body surface area less than 1.0 m (OR 2.6, P=0.02), respectively. The severity of ah correlated with the incidence of gs (r=0.32, P<0.0001), with 7.8% gs for ah0, 14.3% gs for ah1, 60.0% gs for ah2, and 95.5% gs for ah3 (median values). Antibody induction conferred protection from ci (OR 0.31, P=0.008), ct (OR 0.33, P=0.002), and ah (OR 0.12, P<0.001) progression.
By 5 years posttransplant, pediatric renal allografts manifest a substantial burden of tubulointerstitial and microvascular injury. These lesions are associated with donor hypertension, acute inflammation, renal hypoperfusion, obesity, and calcineurin inhibitor toxicity. The pervasiveness and rapid progression of microvascular lesions at 25 to 36 months suggest that attempts at reducing calcineurin inhibitor exposure should be made before two years posttransplant.
在儿科受者中，慢性肾移植损伤的病理生理学尚不清楚。
我们研究了 240 例儿科方案肾移植活检中，在移植后 5 年内肾小管间质、血管和肾小球损伤的演变和决定因素。
慢性肾小管间质损伤（ci、ct）主要发生在移植后 12 个月内，而慢性血管损伤（cv、小动脉玻璃样变[ah]）和全球肾小球硬化（gs）在 25 至 36 个月及以后越来越普遍。慢性间质病变与急性排斥反应和边缘组织学（比值比[OR]2.3，P<0.04）、受者体表面积<1.0m2（OR 3.6，P<0.05）和肥胖（OR 2.0，P<0.03）有关。ct 的决定因素是急性排斥反应（OR 2.6，P=0.02）和急性肾小管坏死（OR 2.8，P<0.04）。血管纤维性内膜增厚和 ah 分别与供者高血压（OR 3.6，P=0.001）和受者体表面积<1.0m（OR 2.6，P=0.02）有关。ah 的严重程度与 gs 的发生率相关（r=0.32，P<0.0001），ah0 为 7.8% gs，ah1 为 14.3% gs，ah2 为 60.0% gs，ah3 为 95.5% gs（中位数）。抗体诱导可预防 ci（OR 0.31，P=0.008）、ct（OR 0.33，P=0.002）和 ah（OR 0.12，P<0.001）的进展。
移植后 5 年，儿童肾移植表现出大量的肾小管间质和微血管损伤。这些病变与供者高血压、急性炎症、肾灌注不足、肥胖和钙调神经磷酸酶抑制剂毒性有关。25 至 36 个月时微血管病变的普遍性和快速进展表明，在移植后两年内应尝试减少钙调神经磷酸酶抑制剂的暴露。
