Özdemir B Handan, Ok Atılgan Alev, Yılmaz Akçay Eda, Özdemir Gökçe, Ayvazoğlu Soy Ebru, Akdur Aydıncan, Haberal Mehmet
From the Department of Pathology, Başkent University Faculty of Medicine, Ankara, Turkey.
Exp Clin Transplant. 2018 Mar;16 Suppl 1(Suppl 1):131-135. doi: 10.6002/ect.TOND-TDTD2017.P27.
Thrombotic microangiopathy is a form of renal capillary injury possibly associated with calcineurin inhibitor toxicity, acute humoral rejection, infections, and recurrent diseases. Here, we examined its incidence in patients diagnosed with acute and chronic active humoral rejection, polyomavirus nephropathy, acute cellular rejection, and immunoglobulin A recurrence.
In total, 272 renal allograft recipients who met the inclusion criteria were reevaluated for presence of renal thrombotic microangiopathy. Thrombotic microangiopathy diagnosis was established by clinical, laboratory, and histologic features. C4d expression in peritubular capillaries was determined. Clinical data were collected from medical records.
Of 272 patients (mean age of 42.8 ± 12.7 years), only 74 patients (27.2%) had de novo thrombotic microangiopathy, which was found in 30/90 patients (33.3%) with acute humoral rejection, 9/51 (17.6%) with acute cellular rejection, 22/53 (41.5%) with chronic active humoral rejection, 10/55 (18.2%) with polyomavirus nephropathy, and 3/23 (13%) with immunoglobulin A nephropathy. Significant differences were shown between therapy type and thrombotic microangiopathy development (P = .02). Patients who received cyclosporine (38.5%) tended to show higher incidence of thrombotic microangiopathy than patients who received tacrolimus (20.7%) or sirolimus (7.7%). Patients with C4d-positive acute humoral (97.6% vs 2.4%) and chronic active humoral rejection (68.2% vs 31.8%) had greater incidence of thrombotic microangiopathy versus those who were C4d-negative. Graft loss was significantly higher in C4d-positive than in C4d-negative thrombotic microangiopathy groups (P < .001). Overall 1-, 3-, and 5-year graft survival was 94%, 85%, and 85% versus 83%, 51%, and 51% in thrombotic microangiopathy-negative versus thrombotic microangiopathy-positive patients (P < .001).
Acute humoral rejection and chronic active humoral rejection were the most common and therefore most important causes of de novo thrombotic microangiopathy in renal transplant patients. Its presence in the renal allograft biopsy should arouse suspicion for underlying acute or chronic active humoral rejection.
血栓性微血管病是一种肾毛细血管损伤形式，可能与钙调神经磷酸酶抑制剂毒性、急性体液性排斥反应、感染及复发性疾病相关。在此，我们研究了其在诊断为急性和慢性活动性体液性排斥反应、多瘤病毒肾病、急性细胞性排斥反应及免疫球蛋白A复发患者中的发生率。
总共对272例符合纳入标准的肾移植受者重新评估肾血栓性微血管病的存在情况。通过临床、实验室及组织学特征确立血栓性微血管病的诊断。测定肾小管周围毛细血管中的C4d表达。从病历中收集临床数据。
在272例患者（平均年龄42.8±12.7岁）中，仅74例患者（27.2%）发生了新发血栓性微血管病，其中30/90例（33.3%）急性体液性排斥反应患者、9/51例（17.6%）急性细胞性排斥反应患者、22/53例（41.5%）慢性活动性体液性排斥反应患者、10/55例（18.2%）多瘤病毒肾病患者及3/23例（13%）免疫球蛋白A肾病患者出现该病症。治疗类型与血栓性微血管病发生之间存在显著差异（P = 0.02）。接受环孢素治疗的患者（38.5%）发生血栓性微血管病的发生率往往高于接受他克莫司（20.7%）或西罗莫司（7.7%）治疗的患者。C4d阳性的急性体液性排斥反应（97.6%对2.4%）和慢性活动性体液性排斥反应（68.2%对31.8%）患者发生血栓性微血管病的发生率高于C4d阴性患者。C4d阳性血栓性微血管病组的移植物丢失率显著高于C4d阴性组（P < 0.001）。血栓性微血管病阴性与阳性患者的总体1年、3年和5年移植物存活率分别为94%、85%和85%以及83%、51%和51%（P < 0.001）。
急性体液性排斥反应和慢性活动性体液性排斥反应是肾移植患者新发血栓性微血管病最常见且因此最重要的原因。其在肾移植活检中的出现应引起对潜在急性或慢性活动性体液性排斥反应的怀疑。
