Broekroelofs J, Stegeman C A, Navis G, Tegzess A M, De Zeeuw D, De Jong P E
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
J Am Soc Nephrol. 1998 Nov;9(11):2075-81. doi: 10.1681/ASN.V9112075.
Chronic progressive renal function loss is a main cause of long-term graft loss after initially successful renal transplantation. Transplanted kidneys share some risk factors for renal function loss, such as hypertension or proteinuria, with diseased native kidneys. Recently, it has been shown that renal function loss is influenced by the angiotensin-converting enzyme (ACE) (insertion/deletion [I/D]) genotype in renal disease in diseased native kidneys. This study examines whether donor or recipient ACE (I/D) genotype is a risk factor for graft loss after renal transplantation. To avoid bias by acute events, graft survival was studied, with patients dying with a functioning graft censored, starting at 12 mo after transplantation in a cohort of 367 patients transplanted between 1987 and 1994 with at least 2 yr of follow-up. Mean follow-up was 58 mo. ACE (I/D) genotype was determined by PCR on stored donor and recipient lymphocytes. Neither donor nor recipient ACE (I/D) genotype was associated with graft survival. However, Cox proportional hazards analysis identified recipient, but not donor, ACE (I/D) genotype D-allele to be independently associated with a shorter time to graft loss in subgroups of patients at high risk for graft loss defined by a creatinine clearance <50 ml/min (n = 108, P = 0.017) or proteinuria > or =0.5 g/24 h at 12 mo (n = 97, P = 0.0051) after transplantation. In conclusion, recipient ACE (I/D) genotype was associated with time to graft loss in a specific high-risk subgroup of the study population. This suggests that the effect of ACE (I/D) genotype on graft survival only becomes apparent when other risk factors are simultaneously present.
慢性进行性肾功能丧失是肾移植最初成功后长期移植物丧失的主要原因。移植肾与患病的天然肾有一些导致肾功能丧失的共同危险因素，如高血压或蛋白尿。最近研究表明，天然肾疾病中肾功能丧失受血管紧张素转换酶（ACE）（插入/缺失[I/D]）基因型影响。本研究旨在探讨供体或受体的ACE（I/D）基因型是否为肾移植后移植物丧失的危险因素。为避免急性事件造成的偏倚，对移植物存活情况进行了研究，将移植后仍有功能的移植物的死亡患者排除，自1987年至1994年间接受移植且至少随访2年的367例患者队列中移植后12个月开始进行研究。平均随访时间为58个月。通过对储存的供体和受体淋巴细胞进行聚合酶链反应（PCR）确定ACE（I/D）基因型。供体和受体的ACE（I/D）基因型均与移植物存活无关。然而，Cox比例风险分析确定，在移植后肌酐清除率<50 ml/min（n = 108，P = 0.017）或12个月时蛋白尿≥0.5 g/24 h（n = 97，P = 0.0051）所定义的高风险移植物丧失患者亚组中，受体而非供体的ACE（I/D）基因型D等位基因与移植物丧失时间缩短独立相关。总之，在研究人群的特定高风险亚组中，受体ACE（I/D）基因型与移植物丧失时间相关。这表明只有当同时存在其他危险因素时，ACE（I/D）基因型对移植物存活的影响才会显现出来。
