Peco-Antić A, Nastić-Mirić D, Babić D, Kostić M
University Children's Hospital, Belgrade.
Srp Arh Celok Lek. 1999 Sep-Oct;127(9-10):305-11.
Renal scarring with and without vesicoureteral reflux (VUR) has been now recognized as an important cause of paediatric hypertension for many years [1-5]. However, its pathogenesis has still remained uncleared. The widespread concept implicated the activation of renin-angiotensin system finding a powerfull support in higher peripheral plasma renin activity (PRA) in children with reflux nephropathy than in controls [6, 7] and in beneficial antihypertensive effects of ACE inhibitors. The latter, in form of captopril, has also been used in captopril test and in renal scintigraphy and isotope renography following the administration of captopril to provide evidence for renin dependent hypertension [8, 9]. Published studies of captopril test have centred on the identification of renovascular as opposed to essential hypertension [10-18, 20-22]. The aim of our study was to assess the usefulness of captopril test in differentiation between hypertensive children with renal scarring from those with essential hypertension. We studied blood pressure (BP) and PRA responses to a single dose of captopril in two groups of hypertensive children. Group A consisted of 29 patients, 14 boys and 15 girls, who had renal scaring as demonstrated by renal 99mTc dimercaptosuccinid acid scan (99m Tc DMSA) and/or intravenous pyelography. Group B included 19 patients, 19 boys and 10 girls who had arterial hypertension, while clinical examination excluded renal and other definable causes of BP elevation, and they were therefore considered to have essential hypertension. At the time of the study all patients had normal glomerular filtration rate and were not salt depleted. They did not receive any antihypertensive medication for at least two weeks. The test was performed in the morning in fasting sitting patients. At the start of the test a small vein in the hand or forearm was cannulated to permit blood sampling. BP was measured 10, 20, and 30 minutes before captopril administration to get baseline BP (mean of these three measurements) and to allow the children to become accustomed to the test procedure. A single oral dose of captopril 0.64 +/- 0.04 mg/kg body weight was given to patients from group A and almost the same dose of captopril, 0.63 +/- 0.05 mg/kg body weight, to patients from group B. The patients remained sitting and BP was measured every 15 minutes during an hour. Blood for PRA was drown in the sitting position (17 patients from group A and 16 patients from group B) before and one hour after the dose of captopril. Samples of blood for basal PRA were collected from 16 patients from group A and in 14 patients from in B in lying position after waking up in the morning. PRA was measured by radioimmunoassay using a commercially available kit, SB-REN 2, from CIS Bio International. According to the criteria of Muller et al. [10] the captopril test was positive if the post-captopril PRA (ng/ml/h) was greater than or equal to 12 with an increase of greater than or equal to 10 and relative increase of greater than or equal to 15% (400% if initial PRA was < 3). The results of our study are presented in Tables 1 and 2 and in Graphs 1 and 2. The age of patients, doses of captopril, initial BP and PRA before the use of captopril did not much differ between studied groups. Fall of BP and PRA increase were highly significant (p < 0.001) both in group A and group B. However, the hypotensive reaction of diastolic BP and MAP were more pronounced in group A (14.45 +/- 1.67% and 15.81 +/- 1.62%) than in group B (6.95 +/- 2.21% and 8.96 +/- 1.75%; p < 0.01), but there were no significant differences in PRA and systolic BP changes and positive results of captopril test between the studied groups. Hypotensive responses of diastolic BP and MAP greater than 10% of initial values were found to be more frequent in group A (79.32% and 79.31%) than in group B (26.61% and 31.57 degrees %; p < 0.001 and p < 0.01). Diastolic BP and MAP were directly related to the dose of cap
伴有或不伴有膀胱输尿管反流(VUR)的肾瘢痕形成多年来一直被认为是儿童高血压的重要原因[1-5]。然而,其发病机制仍不清楚。普遍的观点认为肾素-血管紧张素系统的激活在反流性肾病患儿外周血浆肾素活性(PRA)高于对照组[6,7]以及ACE抑制剂的有益降压作用中得到了有力支持。后者以卡托普利的形式也被用于卡托普利试验以及在给予卡托普利后的肾闪烁显像和同位素肾图检查中,以提供肾素依赖性高血压的证据[8,9]。已发表的关于卡托普利试验的研究主要集中在肾血管性高血压与原发性高血压的鉴别上[10-18,20-22]。我们研究的目的是评估卡托普利试验在鉴别患有肾瘢痕的高血压儿童与原发性高血压儿童中的有用性。我们研究了两组高血压儿童对单剂量卡托普利的血压(BP)和PRA反应。A组由29例患者组成,14名男孩和15名女孩,经肾99mTc二巯基丁二酸扫描(99mTc DMSA)和/或静脉肾盂造影证实有肾瘢痕。B组包括19例患者,19名男孩和10名女孩,患有动脉高血压,而临床检查排除了肾脏及其他可明确的血压升高原因,因此他们被认为患有原发性高血压。在研究时,所有患者的肾小球滤过率正常且未出现盐耗竭。他们至少两周未服用任何降压药物。试验在早晨对空腹坐着的患者进行。在试验开始时,在手或前臂的一条小静脉插管以便采血。在给予卡托普利前10、20和30分钟测量血压以获得基础血压(这三次测量的平均值),并让儿童适应试验程序。给予A组患者单口服剂量卡托普利0.64±0.04mg/kg体重,给予B组患者几乎相同剂量的卡托普利,0.63±0.05mg/kg体重。患者保持坐姿,在一小时内每15分钟测量一次血压。在给予卡托普利前及给药后一小时,在坐姿下采集用于PRA检测的血样(A组17例患者,B组16例患者)。早晨醒来后,从A组16例患者和B组14例患者的卧位采集基础PRA血样。使用CIS Bio International公司的市售试剂盒SB-REN 2通过放射免疫测定法测量PRA。根据Muller等人[10]的标准,如果卡托普利后PRA(ng/ml/h)大于或等于12,增加大于或等于10且相对增加大于或等于15%(如果初始PRA<3,则为400%),则卡托普利试验为阳性。我们的研究结果列于表1和表2以及图1和图2中。研究组之间患者的年龄、卡托普利剂量、使用卡托普利前的初始血压和PRA差异不大。A组和B组的血压下降和PRA升高均非常显著(p<0.001)。然而,A组舒张压BP和平均动脉压MAP的降压反应(14.45±1.67%和15.81±1.62%)比B组(6.95±2.21%和8.96±1.75%;p<0.01)更明显,但研究组之间PRA和收缩压变化以及卡托普利试验阳性结果无显著差异。发现A组舒张压BP和MAP的降压反应大于初始值的10%比B组更频繁(79.32%和79.31%比26.61%和31.57%;p<0.001和p<0.01)。舒张压BP和MAP与卡托普利剂量直接相关