Lufft V, Kliem V, Hamkens A, Bleck J S, Eisenberger U, Petersen R, Ehlerding G, Maschek H, Pichlmayr R, Brunkhorst R
Abt. Nephrologie, Gastroenterologie, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule, Hannover, Germany.
Clin Transplant. 1998 Oct;12(5):409-15.
Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients.
28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively.
Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated.
Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.
血管紧张素转换酶（ACE）抑制剂已成功用于肾移植（RTx）后蛋白尿的治疗。肾移植患者中抗蛋白尿作用（APE）存在巨大个体差异的可能原因尚未得到研究。
对28例肾移植后持续性蛋白尿超过1.25 g/d的患者进行前瞻性治疗，给予对全身动脉血压无效的福辛普利剂量（10 - 15 mg/d）。在开始使用福辛普利之前，所有患者均进行了肾移植活检，并通过双功超声排除了肾移植动脉狭窄。在开始ACE抑制治疗前、治疗3个月和8个月后测量血清肌酐和蛋白尿，通过24小时测量和重复的即时测量来控制平均动脉压。蛋白尿的减少分别与肾组织学、血清肌酐、肌酐清除率、平均动脉血压、治疗前钠排泄以及治疗期间这些参数的相对变化相关。
8/28例患者因包括血清肌酐升高（n = 4）在内的副作用而不得不停止治疗。3例患者因不依从被排除。在其余患者（n = 17）中，蛋白尿分别在3个月和8个月后从2.94 ± 1.66降至1.82 ± 1.39和2.48 ± 3.05 g/d，均值 ± 标准差。APE与良性肾硬化、间质纤维化和肾小管萎缩的程度之间存在显著负相关。未发现APE与任何其他参数之间存在相关性。
福辛普利可有效应用于蛋白尿性肾移植受者的一个亚组。然而，由于出现副作用的患者比例较高，必须进行仔细监测。我们的结果表明，慢性形态学损伤程度越低，抗蛋白尿作用越强。因此，移植肾预先存在的经组织学证实的损伤程度可作为肾移植后ACE抑制剂治疗抗蛋白尿疗效的一个指标。
