Comparison of histopathological characteristics of allograft biopsy between responder and non-responder to antiproteinuric effect of angiotensin-converting enzyme inhibitor (ACEI)

Abstract:  Angiotensin-converting enzyme inhibitor (ACEI) has become recognized as agents that have renoprotective effects in the treatment of progressive renal diseases including post-transplant kidneys. Previously we demonstrated the safety and effectiveness of ACEI treatment on the hypertensive proteinuric post-transplant patients ( N  = 10) who had been followed up for 12 months. However, not all patients show good response in urinary protein reduction. We aimed to analyse the histopathological factor(s) affecting the responsiveness of proteinuria to ACEI treatment. Fourteen post-transplant patients with proteinuria who were treated with ACEI and underwent allograft biopsy were analysed. Eight patients showed 50% or more reduction in proteinuria (responder). The other 6 patients showed less (< 50%) reduction in proteinuria (non-responder). There was no difference in clinical characteristics (BP, renal function, donor age, recipient body mass index), dietary sodium or protein intake, and diuretic use between the two groups. As a histopathological characteristic, glomerular size in responder group was significantly larger than that in non-responder group. This suggests that the large glomerular size at least partly contributes to the responsiveness in urinary protein reduction to ACEI treatment in kidney allograft recipients with proteinuria.     

Benazepril slows progression of renal dysfunction in patients with non-diabetic renal disease

AIM: The present study examined the effects of benazepril, an angiotensin-converting enzyme inhibitor, on the progression of renal insufficiency in patients with non-diabetic renal disease. METHODS: Fifteen patients with non-diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL were given either benazepril (2.5-5 mg) or placebo once daily for 1 year in a random crossover manner. In both periods, antihypertensive medications were increased if blood pressure was greater than 130/85 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study period. RESULTS: Blood pressure was similar when comparing the benazepril and the placebo periods (128+/-12/83+/-6 vs 129+/-10/83+/-7 mmHg). Serum Cr significantly increased from 1.62+/-0.18 to 1.72+/-0.30 mg/dL (P=0.036) during the placebo period, while there was no statistically significant increase in serum Cr during the benazepril period (from 1.67+/-0.17 to 1.71+/-0.27 mg/dL). The slope of decrease of the reciprocal of serum Cr was steeper in the placebo period than in the benazepril period (-0.073+/-0.067 vs-0.025+/-0.096/year, P=0.014). Urinary protein excretion was lower during the benazepril period than during the placebo period (0.57+/-0.60 vs 1.00+/-0.85 g/gCr, P=0.006). Serum K was significantly higher in the benazepril period than in the placebo period (4.4+/-0.5 vs 4.2+/-0.5 mEq/L, P<0.001), but no patient discontinued benazepril therapy as a result of hyperkalemia. CONCLUSION: Long-term benazepril treatment decreased the progression of renal dysfunction in patients with non-diabetic renal disease by a mechanism that is independent of blood pressure reduction.     

高血压患者用血管紧张素转换酶抑制剂治疗时的骨密度

目的 探讨血管紧张素转换蘸抑制剂(ACEI)对人体中轴骨骨量的影响。方法 我们将128例绝经后妇女分为4组：A组;正常血压组46例;B组：高血压ACEI短程(<5年,中位数为3年)治疗组18例;C组：高血压ACEI长程(≥5年．中位数7．5年)治疗组30例;D组：高血压心痛定治疗组34。采用双能X线吸收法测量其腰椎正侧位(APL2-4、LatL2-4)和左股骨近端各区(包括Neck、Troch、Inter、Total和Ward's)的骨密度,并检测了部分患血清BGP和晨尿羟脯氨酿(Hop／Cr)等生化指标。结果 B组和C组APL2-4．骨密度分别明显高于D组;B组和C组股骨近端除Troch外其他各区骨密度均分别明显高于D组,且C组尚显高于A组,有显差异(P<0．05);同A组和D组相比,B组和C组Troch和LatL2-4骨密度亦有增加趋势。此外,C组骨密度比B组有增高趋势,但差异无显意义。B组和C组血清BGP和晨尿HOP水平分别明显低于A组或D组(P<0．05),但B、C二组间无显差异;各组间血清钙、磷、ALP水平无显差异,结论 ACEI对骨量具有一定的保持作用．特别适用于老年女性高血压患。     

The renal functional and structural consequences of corticosteroid and angiotensin-converting enzyme inhibitor therapy in chronic puromycin aminonucleoside nephropathy

Glomerular diseases are characterized by increased urinary protein excretion. Treatment of this abnormality frequently involves administration of corticosteroids and angiotensin-converting enzyme inhibitors. There has been much recent interest in the potential impact of these drugs on progressive renal dysfunction, since they have opposing effects on intraglomerular hemodynamics. Therefore, we investigated the effect of methylprednisolone or captopril treatment on animals with chronic puromycin aminonucleoside nephropathy. In rats given a single injection of puromycin aminonucleoside, 15 mg/100 g body weight, both methylprednisolone and captopril significantly reduced proteinuria at 6 months [83±14 untreated (n=7), 34±6 with methylprednisolone (n=8), and 6±1 mg/24h with captopril (n=5),P<0.001]. Segmental glomerulosclerosis occurred with equal frequency in the untreated (7.8±2.3%) and methylprednisolone-treated rats (5.0±1.11%), but was significantly reduced by the administration of captopril (1.0±0.5%,P<0.001). We conclude that in chronic puromycin aminonucleoside nephropathy, treatment with corticosteroids reduces proteinuria without increasing the incidence of segmental glomerulosclerosis. Therapy with an angiotensin-converting enzyme inhibitor substantially decreases proteinuria and lessens the severity of glomerular scarring.     

Bone marrow transplant nephropathy successfully treated with angiotensin-converting enzyme inhibitor

We report a patient who developed chronic renal failure 11 months after an allogeneic hematopoietic stem-cell transplantation (HSCT) for Ph1⁺ acute lymphocytic leukemia. Renal biopsy showed typical pathological findings compatible with a bone marrow transplant nephropathy (BMT nephropathy). The general course of BMT nephropathy is slowly progressive, eventually reaching endstage renal failure. Intervention therapy with an angiotensin-converting enzyme inhibitor (ACE-I), temocapril, was started for this patient, based on several experimental reports showing the protective effects of ACE-Is on BMT nephropathy. After the induction of ACE-I in this patient, the rate of regression of renal function was significantly reduced and his serum creatinine was maintained at almost the same level for 18 months. Although the course of observation in this patient was short, we clearly showed the effects of an ACE-I on preventing BMT nephropathy from progressing to endstage renal failure in a human rather than in an experimental model.     

Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate

BACKGROUND: Up to seven in every 1000 patients experience angioedema from angiotensin-converting enzyme (ACE) inhibitors, even after many years of use. In 2003, every 20th Norwegian used an ACE inhibitor. CASE REPORT: A 61-year-old woman with chronic obstructive pulmonary disease and a past acute myocardial infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema of the arytenoids. Inspiratory stridor was heard and the patient could not speak. She became increasingly uneasy and restless. Berinert complement 1 (C1) inhibitor concentrate (1500 units) was administered i.v. Over the following 20 min, stridor gradually subsided, the patient calmed and she was able to talk. DISCUSSION: ACE inhibitor-provoked angioedema shares many clinical features with hereditary angioedema (HAE), including a limited effect of steroids, antihistamines and epinephrine. HAE, caused by excess bradykinin formation as a result of C1 inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1 inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor-provoked angioedema have normal C1 inhibitor values, as in our patient, excess bradykinin is probably important as ACE breaks down bradykinin. It is unknown why ACE inhibitor-provoked angioedema appears in some and sometimes after many years of use. CONCLUSION: We believe that C1 inhibitor was effective in reversing the ACE inhibitor-induced angioedema in our patient.     

Angiotensin converting enzyme inhibitor use soon after renal transplantation: a randomized, double-blinded placebo-controlled safety study

Activation of the renin-angiotensin system (RAS) followed by increased inflammatory cytokines may be important in the pathogenesis of chronic allograft dysfunction. As many renal transplant recipients show chronic changes on biopsy within the first year, early RAS blockade with angiotensin converting enzyme inhibitor (ACEI) could be beneficial. However, it remains unclear that early ACEI use is safe. We conducted a prospective, randomized, placebo-controlled trial to assess the safety of enalapril 5 mg during the early post-transplant period. Subjects took the study medication for six months. Primary endpoints were serum potassium (K) >5.9 mEq/L and 30% increase in baseline creatinine. A total of 53 subjects were randomized, and of them, 27 received the study drug. Twenty-nine subjects, 14 ACEI and 15 controls, completed the six-month protocol without reaching an endpoint. Patients on ACEI had higher K and higher BUN at six months. Serum creatinine, hematocrit, and urinary protein were not different. There was no difference in urinary TGF-β1. Twenty-four subjects reached study endpoints. When the common clinical endpoints of elevated creatinine and hyperkalemia were combined, ACEI group had significantly increased endpoints vs. control (10/13, 77% vs. 5/11, 45%, p < 0.05). We conclude that ACEI use in the early post-transplant period can be safe but patients must be carefully selected and monitored for elevations in serum creatinine and potassium. Whether early ACEI is beneficial in preserving allograft function requires further study.     

Comparison of the renal effects of different angiotensin-converting enzyme inhibitors in patients with chronic renal diseases

Background. Angiotensin-converting enzyme inhibitors (ACE-Is) are important agents for preserving renal function in patients with renal diseases. However, the choice of which ACE-I to employ for the treatment of renal disease has not yet been clarified. This study compared the renal effects of enalapril with those of five other ACE-Is in patients with chronic renal diseases. Methods. One hundred and twenty-eight patients with various renal diseases were randomly assigned to six groups according to the ACE-I used: group 1, alacepril (75 mg/day; n = 20); group 2, captopril (37.5 mg/day; n = 19); group 3, cilazapril (1.0 mg/day; n = 23); group 4, delapril (30 mg/day; n = 22); group 5, enalapril (5.0 mg/day; n = 20); and group 6, temocapril (2.0 mg/day; n = 24). Doses of the ACE-I adjusted-converting to the renal function showed similar effects in decreasing blood pressure. Each ACE-I was administered to the patients for 4 months, with monthly examinations. Twenty-four patients dropped out, for various reasons; therefore, results for 104 patients were finally analyzed (group 1, n = 16; group 2, n = 11; group 3, n = 22; group 4, n = 21; group 5, n = 12; group 6, n = 22). Results. There were no differences in absolute or percent changes in mean arterial pressure (MAP), plasma aldosterone (ALDO), the urinary excretion of protein (U-P) and albumin (U-ALB), 24-h creatinine clearance (24-h Ccr), plasma renin activity (PRA), and serum potassium (K) between enalapril and the other ACE-Is, although significant decreases from baseline values in MAP, ALDO, U-P, U-ALB, and 24-h Ccr, and increases in PRA and serum K from baseline values were observed after the administration of enalapril and the other ACE-Is. Conclusions. These results indicated that the renal effects of enalapril were similar to those of the other ACE-Is tested, and suggested, therefore, that any one of the class of ACE-Is could be chosen with the choice being dependent on that considered to lead to best compliance for the patient. The beneficial effects of the class of ACE-Is in patients with renal disease would be expected to be similar. Received: September 6, 2001 / Accepted: November 14, 2001     

Dual blockade of the renin-angiotensin system compared with a 50% increase in the dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood pressure.

BACKGROUND: Several publications in the past 2 years have demonstrated that combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor antagonist (AIIRA) are more effective in reducing blood pressure and proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This study compares the effect of increasing the ACEI dose by 50% with that of adding an AIIRA to a standard ACEI dose. METHODS: This study was designed as part of a previous comparison of ACEI with ACEI plus candesartan. Directly after completion of the randomized intervention periods of that study, the dose of ACEI was increased by 50% in all patients. Proteinuria and blood pressure were compared in both groups of patients in the three periods, on standard ACEI, on ACEI plus candesartan and on a dose of ACEI increased by 50%. RESULTS: No significant differences in the primary end-point proteinuria or secondary end-points were observed when the ACEI dose was increased by 50%. Proteinuria was 1.8 g in 24 h on candesartan and ACEI and 2.4 g in 24 h when the ACEI dose was increased by 50% (P<0.02). Systolic blood pressure was 126.6 mmHg on candesartan and ACEI and 134.47 mmHg when the ACEI dose was increased by 50% (P<0.002). Diastolic blood pressure, serum creatinine, urea and potassium were not different between groups. CONCLUSIONS: Standard ACEI plus candesartan is more effective in reducing systolic blood pressure and proteinuria than a 50% increase in ACEI dose. This has implications for the prevention of renal failure in chronic renal disease.     

Haemodynamic effects of an angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist during hypovolaemia in the anaesthetized pig

Background. Renin–angiotensin system antagonists, eitherangiotensin-converting enzyme (ACE) inhibitors or angiotensinII receptor (AT₁) antagonists, may interfere with regulationof arterial pressure during anaesthesia. This study aimed tocompare the haemodynamic profile of anaesthetized pigs, whichwere subjected to haemorrhage in the presence of the ACE inhibitorenalaprilat or the AT₁ antagonist valsartan. Methods. Thirty-six pigs were assigned randomly to placebo,enalaprilat or valsartan groups. After a 30-min period of stabilizationfollowing anaesthesia and injection of the study drug, the animalswere bled in two equal steps of 20% of their estimated bloodvolume (20% BV and 40% BV). Results. After bleeding of 20% BV, the mean arterial pressure(MAP) decreased significantly but similarly in each group (20–25%)but the placebo and the enalaprilat groups had a significantdecrease in cardiac index (CI, 22% and 16%, respectively) withoutsignificant change in systemic vascular resistance (SVR). Conversely,in the valsartan group, SVR decreased significantly (23%, P<0.02vs other groups) without significant change in CI (–4%).After bleeding of 40% BV, the CI decreased significantly comparedwith 20% BV in the three groups (19% in the placebo and enalaprilatgroups, 14% in the valsartan group) but the MAP decreased significantlyin the enalaprilat group only (23%). The SVR increased significantlyin the placebo group (P<0.01 vs each of the other groups),but there were no differences in the change in SVR between theother groups. Conclusion. Blockade of the renin–angiotensin system byeither enalaprilat or valsartan leads to a similar decreasein arterial pressure during anaesthesia and haemorrhage butthe haemodynamic profiles are quite different. Br J Anaesth 2002; 89: 599–604     

Sperm angiotensin-converting enzyme activity in Chernobyl victims and patients with chronic prostatitis

Summary. The method for determination of angiotensin-converting enzyme activity in human spermatozoa and seminal plasma was developed. The number of total and active-motile spermatozoa was shown to be lower in Chernobyl victims than in healthy donors. The specific activity of angiotensin-converting enzyme in spermatozoa from Chernobyl victims was 12 times higher than that in donors. Similar results, although to a lesser extent, were observed in patients with chronic prostatitis. In contrast, the enzyme activity in blood serum and seminal plasma was identical for all subjects investigated.     

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos

Aim:   The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus.
Methods:   A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method.
Results:   Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P  ≤ 0.044). In addition, female patients with macroalbuminuria without dialysis showed no significant differences with patients undergoing dialysis.
Conclusion:   The ACE DD genotype is a risk factor for the development of renal disease in Mexican Mestizo females with type 2 diabetes, indicating a possible DD genotype-associated sex effect in renal disease.     

血管紧张素转换酶抑制剂对单侧动脉粥样硬化性肾动脉狭窄患者肾功能的影响

目的 观察血管紧张素转换酶抑制剂(ACEI)对单侧动脉粥样硬化性肾动脉狭窄(ARAS)患者肾功能的影响&#65377;方法 结合临床表现及肾动脉造影结果诊断单侧ARAS患者共49例, 分为ACEI组20例与对照组29例&#65377;记录基础血压, 检测Scr&#65380; BUN&#65380; Alb, 以MDRD公式计算估计肾小球滤过率(eGFR),行肾动脉彩超检查测量肾脏阻力指数(RI)&#65377;每月测量血压,每6个月复查Scr&#65380;Urea&#65380;Alb并计算eGFR, 观察两组患者随访期间肾功能变化&#65377; 结果 两组患者试验前一般临床资料无显著性差异&#65377;平均随访9.9个月,随访期间两组血压均无明显变化(P > 0.05)&#65377;与试验前比,对照组eGFR无明显变化[(74.5±18.3 )ml·min^-1·(相似文献   

Acute renal responses to angiotensin-converting enzyme inhibition in the neonatal pig

Pharmacological interruption or genetic disruption of the renin-angiotensin system before completion of nephrogenesis produces papillary atrophy and an impaired urinary concentrating ability. The mechanisms involved are yet to be elucidated, but renal hypoperfusion and subsequent ischemia, particularly to the immature renal medulla, may be hypothesized. The acute intrarenal responses to angiotensin-converting enzyme (ACE) inhibition in the newborn piglet were thus investigated by means of regional blood flow distribution, renal interstitial hydrostatic pressure (RIHP), and medullary oxygen tension (PO₂) in the anesthetised 4- to 5-day-old piglet. Moreover, the calcium antagonist nifedipine and the nitric oxide synthesis inhibitor L-NAME were also given in order to reduce renal blood flow by other means. The drugs were given intravenously in equipotent pressor doses, mimicking intraperitoneal injections in neonatal rats. Enalaprilat (200 μg/kg) reduced mean arterial pressure (MAP) by 14±10% (mean±SD, P=0.006) and RIHP by 18±18% (P=0.001), whereas total renal blood flow and medullary PO₂ remained unchanged. In contrast, nifedipine (0.5 mg/kg) reduced MAP and RIHP by 39±8% and 38±14%, respectively, total and regional blood flows by 30%–60%, and medullary PO₂ by 46±29% (P=0.001). Acute administration of L-NAME (15 mg/kg) increased MAP by 27±10% (P=0.0005), whereas RIHP and renal blood flow decreased by 20%–50%, resulting in a reduction of the medullary PO₂ by 10±12% (P=0.05). We conclude that the renal abnormalities observed after neonatal ACE inhibition are not likely to be caused by renal ischemia. Received: 5 October 1999 / Revised: 21 March 2000 / Accepted: 22 March 2000     

ACE在皮肤组织损伤修复与再生中作用的研究

血管紧张素转化酶（angiot ensin-converting enzyme,ACE）是肾素-血管紧张素系统（renin-angiotensin system,RAS）激活过程中的关键性限速酶之一,可催化血管紧张素Ⅰ水解生成RAS最重要的活性产物血管紧张素Ⅱ。ACE也可使具有扩张血管反应的缓激肽生成苯丙-精二肽,还可直接作用于肾上腺皮质促进醛固酮分泌。近年来发现ACE除了降解血管紧张素I和缓激肽外,还能降解其它产物如：β-内啡肽、P物质、Ac-SDPK等。同时,ACE和中性内肽酶（neutral endopeptidase,NEP）作为终止皮肤神经-内分泌介质作用的关键酶可调控皮肤细胞的存活、创伤愈合和组织再生。本文主要阐述近年来有关ACE及其底物在皮肤组织损伤修复与再生中作用的相关研究。     

甲状腺功能亢进症患者行食管癌根治术后并发甲状腺危象

甲状腺危象是甲状腺功能亢进症（简称甲亢）恶化时的严重表现。甲状腺危象的发生与感染、机体内环境改变、手术应激等因素有关。一旦发生可危及患者生命,故应积极救治。报道1例甲亢患者行食管癌根治术后发生甲状腺危象的分析、处理及转归.     

Barriers to blood pressure control and angiotensin enzyme inhibitor use in Canadian patients with chronic renal insufficiency.

BACKGROUND: Current recommendations for the management of chronic renal insufficiency (CRI) include the use of angiotensin-converting enzyme inhibitors (ACEI) and achieving target blood pressure control. We designed this study to describe the use of these therapeutic strategies, and to investigate barriers to their implementation. METHODS: This was a prospective study of 304 consecutive CRI patients, seen at follow-up in four nephrology clinics across Canada. The use of blood pressure control and antihypertensive medication (AHM) in each of these clinics was recorded, and a questionnaire was administered to nephrologists to determine the basis for decisions concerning AHM regimens and ACEI use/non-use. RESULTS: Mean age was 60.8+/-15.7 years, mean creatinine clearance was 30.3+/-18 ml/min, and underlying renal diseases were similar to registry data. Mean arterial pressure (MAP) achieved was 99.4+/-14.4 and 98.9+/-11.9 mmHg in individuals with >1 and 相似文献