Rolla Davide, Fontana Iris, Ravetti Jean Louis, Marsano Luigina, Bellino Diego, Panaro Laura, Ansaldo Francesca, Mathiasen Lisa, Storace Giulia, Trezzi Matteo
Divisione di Nefrologia - Dialisi -Trapianto, Ospedale Sant'Andrea, La Spezia, Italy.
Divisione di Chirurgia Vascolare e Trapianto di rene, Azienda Ospedaliera Universitaria San Martino, Genova, Italy.
J Renal Inj Prev. 2015 Nov 30;4(4):135-8. doi: 10.12861/jrip.2015.28. eCollection 2015.
Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH.
Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD.
血栓性微血管病(TMA)是肾移植的一种严重并发症,主要与钙调神经磷酸酶抑制剂(CNI)的促血栓形成作用有关。一部分TMA(29%-38%)仅局限于移植肾。病例1:一名患有常染色体显性多囊肾病(ADPKD)的年轻女性接受了肾移植。2个月后,她出现肾功能缓慢恶化(血清肌酐从1.9升至3.1mg/dl),无溶血尿毒综合征(HUS)的血液学表现;仅检测到乳酸脱氢酶(LDH)酶短暂升高。肾活检显示为TMA:停用他克莫司并进行了血浆置换。肾功能恢复(血清肌酐1.9mg/dl)。通过筛查血栓形成倾向,我们发现了莱顿因子V基因的突变。病例2:一名患有ADPKD的男性接受了肾移植,移植肾功能延迟;首次活检显示急性肾小管坏死,但第二次活检显示为TMA,同时未检测到HUS的血液学参数改变。我们仅观察到乳酸脱氢酶(LDH)水平略有升高。他克莫司剂量减半并进行了血浆置换:LDH水平在10天内恢复正常,肾功能改善(血清肌酐从9降至2.9mg/dl)。我们发现了凝血酶原基因的突变。只有肾活检才能明确TMA的诊断,但有必要注意LDH水平的轻度升高。
CNI和mTOR抑制剂的促血栓形成作用、编码因子H或I的基因突变、抗心磷脂抗体、血管排斥反应、巨细胞病毒感染被认为是引发TMA的因素;我们检测到因子II和莱顿因子V的突变,这是ADPKD患者发生TMA的易患因素。