Focal segmental glomerulosclerosis complicating solitary kidney

A 78-year old woman with complicating solitary kidney had nephrotic syndrome. Renal biopsy specimens showed focal segmental glomerulosclerosis (FSGS). First, the patient was treated with angiotensin receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI). Proteinuria decreased from 10 to 6 g/day, but overall the nephrotic syndrome did not improve. Additional treatment with prednisolone and cyclosporine reduced proteinuria to less than 1.0 g/day. We report that combination therapy with ARB, ACEI, prednisolone, and cyclosporine was successful for FSGS complicating solitary kidney.     

Additive antiproteinuric effect of angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor in patients with chronic glomerulonephritis

Angiotensin II type-1 receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) have been thought to be effective for reducing proteinuria in patients with chronic glomerulonephritis. Recently, an additive effect of these two types of angiotensin blockers has been reported in patients with IgA nephropathy, but the mechanism responsible for the effect has not yet been determined. In this study, we examined additive effect of these two drugs in chronic glomerulonephritis patients. Ten patients with biopsy-proven primary glomerulonephritis (eight IgA nephropathy patients, two membranous nephropathy patients), non-nephrotic proteinuria (protein, 0.5 to 3.5 g/day) received candesartan cilexetil (2 or 4 mg) for 8 weeks. After the 8 weeks, a combination of perindopril erbumine (1 or 2 mg) and candesartan cilexetil was administered to the patients. Perindopril was stopped after the 8-week administration of the two drugs. Candesartan alone reduced proteinuria by 13%. Combination of these two drugs induced a more remarkable reduction of proteinuria (48%; p < 0.05 vs other periods). The decrease in mean blood pressure by the combination therapy was significantly correlated with the decrease in proteinuria. The combination of drugs also reduced the amount of urinary type-IV collagen excretion. An additive effect of ACEI and ARB on proteinuria and urinary type-IV collagen excretion was recognized in patients with chronic glomerulonephritis.     

Successful effect of triple blockade of renin–angiotensin–aldosterone system on massive proteinuria in a patient with chronic kidney disease

A patient with chronic kidney disease (CKD) due to membranous nephropathy with daily urinary protein excretion exceeding 5 g did not respond well to dual therapy with an angiotensin converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB). Addition of the mineralocorticoid receptor blocker (MRB), spironolactone, led to moderate reduction in daily urinary protein excretion. However, spironolactone had to be inevitably discontinued due to gynecomastia. Replacement of spironolactone with the selective MRB, eplerenone, added to the preceding treatment with ACE-I and ARB, resulted in remarkable reduction of daily urinary protein excretion to less than 0.2 g. This case suggests that triple blockade of renin–angiotensin–aldosterone (RAA) system with ACE-I, ARB, and MRB could be useful for CKD patients with massive proteinuria.     

Treatment strategies in patients with chronic renal disease: ACE inhibitors,angiotensin receptor antagonists,or both?

We discuss the evidence supporting the use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), or the combination of both in children with chronic renal disease. Several large-scale, prospective, randomized studies with clinical end points have been performed in adult patients, but studies in children are relatively scarce. In adult patients with chronic renal diseases, ACEI clearly delay the progression of chronic non-diabetic renal diseases, and nephropathy in patients with type 1 diabetes. The benefits of ACEI are most apparent in glomerular diseases with marked proteinuria but extend also to kidney diseases with lower proteinuria. This notion is also supported by several smaller or retrospective trials in children. Therefore, ACEI should be given to children with chronic renal diseases, particularly if high blood pressure and/or proteinuria are present. In adults, large-scale trials have documented that ARB exert similar effects as ACEI but tend to exert fewer undesired side effects. Data on ARB in children with chronic renal disease are still very scarce, but these substances offer an alternative for patients who cannot tolerate ACEI due to unwarranted side effects. Combination therapy with ARB plus ACEI may be more effective than either drug class alone. However, we will need the results of further long-term prospective clinical studies, as well as a better understanding of the role of the AT₂ receptor, before combination therapy can be widely recommended. A trial of ARB plus ACEI is justified in selected patients if blood pressure and/or proteinuria cannot adequately be lowered by ACEI or ARB alone.     

Alport综合征精准诊治进展

Alport综合征是由于编码Ⅳ型胶原α3/α4/α5链的基因突变导致的遗传性肾脏疾病,临床上表现为血尿、蛋白尿及进行性肾衰竭,部分患者合并耳聋和眼部改变。随着医学技术的进步,Alport综合征的诊断逐渐精确,诊断依据从最初的临床表现,到肾组织电镜典型的肾小球基底膜病理改变,再到目前广泛应用的基因突变检测。目前认为Alport综合征是可以治疗的疾病,尽早应用血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB)可以推迟Alport综合征肾衰竭发生。     

Dual blockade of the rennin–angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis

Background Proteinuria and hypertension are predictors of poor renal outcome in chronic glomerulonephritis (CGN). At the same level of blood pressure (BP) control, we evaluated which is superior, dual blockade of the rennin–angiotensin system (RAS) with both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 (AT-1) receptor blockade (ARB) or single blockade of ARB to reduce proteinuria and to preserve renal function in patients with CGN. Methods In this prospective, parallel, open study of 86 patients with CGN, we compared the effects on proteinuria and renal functions of 36 months with comparable blood pressure (BP) control achieved by candesartan cilexetil (candesartan, 4–12 mg/day) or benazepril hydrochrolide (benazepril, 2.5–10 mg/day) with candesartan (4 mg/day). Aiming at BP 125/75 mmHg or less, the dose of candesartan (single blockade) or benazepril (dual blockade) was increased. Results Dual blockade decreased proteinuria more than single blockade with ARB (−42.3 vs. −60.5%, P < 0.01). Renal plasma flow (RPF) and glomerular filtration fraction (GFR) did not change significantly in either group. The filtration fraction (FF) decreased dual blockade more than single blockade (−1.7 vs. −19.0%, P < 0.05). Decreased FF was associated with the reduction of proteinuria (P < 0.05). Six percent of patients with dual blockade were not able to continue the study because of a dry cough. Conclusion Long-term dual blockade decreased proteinuria more than single blockade with ARB. Although ARB and ACEI have a glomerular size-selective function for proteinuria, a greater antiproteinuric effect may depend on renal hemodynamics, especially FF. Increased levels of bradykinin after ACEI can decrease FF and ameliorate proteinuria. Dry cough is a significant adverse effect of ACE inhibitor.     

双倍剂量ARB治疗难治性肾病综合征的临床研究

目的 难治性肾病综合征一直是世界医学的难题.本研究选择用双倍剂量血管紧张素Ⅱ受体1阻滞剂(ARB)治疗糖皮质激素和免疫抑制剂治疗失败的难治性肾病综合征,观察其临床效果. 方法 本试验为开放性自身对照临床研究.19例入选病人,符合肾病综合征的诊断标准并已排除继发性肾损害的可能.患者中病程最短为7个月,最长达24个月,均属激素联合免疫抑制剂治疗无效者.肾脏病理情况:微小病变型肾炎3例,系膜增生型肾炎3例,IgA肾病2例,膜性肾病4例,局灶节段硬化性肾小球肾炎4例.治疗方法 :11例使用缬沙坦(80mg/片),8例使用氯沙坦(50mg/片),从每日1片开始,2周后剂量增至每日2片目标剂量,自达到目标剂量起临床观察3个月.观察指标:用药前及用药后每2周检测尿常规和24小时尿蛋白、血清白蛋白(Alb)、血肌酐(Scr)、血清钾、钠、氯及谷丙转氨酶(ALT)、谷草转氨酶(AST)、直接胆红素(dBil)、间接胆红素(iBil);常规观察并记录患者水肿情况和右上肢血压;全程进行不良反应监测.按尿蛋白减少的量和降低的幅度作为疗效的评定标准:完全缓解:经治疗后尿蛋白阴转,定量检查＜0.2g/d;显著缓解:治疗后尿蛋白定量≤1g/d,或虽＞1g/d,但比治疗前减少≥50%;部分缓解:治疗后尿蛋白定量≤3g/d,或虽＞3g/d,但比治疗前减少≥50%;无效:治疗后尿蛋白无明显改善.统计数据分析用SPSS统计软件进行处理. 方法 血清蛋白水平:ARB治疗前患者血清白蛋白检测值为16.35～31.84克,平均26.96±4.72克;观察期结束时血清白蛋白值为24.71～38.82克,平均31.75±3.57克,治疗前后均值统计学差异有显著性意义(p<0.05).24尿蛋白定量:治疗前检测值为3.53～7.82克,平均4.65±1.03克;缬沙坦或氯沙坦治疗后3个月检测值为1.75～5.49克,平均2.84±1.76克,治疗前后均值统计学有显著差异(p<0.05).疗效情况:所有病例中无1例完全缓解,显著缓解5例(26.3%),部分缓解11例(57.9%);无效3例(15.8%),将前三项视为治疗有效,则有效率为84.2%. 仅1例出现短期低血压症状.结论 对于激素联合免疫抑制剂治疗无效的原发性肾病综合征,部分患者使用双倍剂量ARB治疗可减少尿蛋白排泄量,提高血清白蛋白水平.     

AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat

BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. METHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.     

Alport syndrome: the effects of spironolactone on proteinuria and urinary TGF-β1

Background

Alport syndrome (AS) is a progressive hereditary glomerular disease. Recent data indicate that aldosterone promotes fibrosis mediated by the transforming growth factor-β1 (TGF-β1) pathway, which may worsen proteinuria. Spironolactone (SP) antagonizes aldosterone and this study aimed to evaluate the efficacy of SP in reducing proteinuria and urinary TGF-β1 excretion in proteinuric AS patients.

Methods

The study involved ten children with AS, normal renal function, and persistent proteinuria (>6 months; uPr/uCr ratio >1). SP 25 mg once a day for 6 months was added to existing ACE inhibitor treatment with or without angiotensin-II receptor blockade. Urine and blood samples were examined monthly. Urinary TGF-β1 levels were measured twice before and three times during SP treatment. Plasma renin activity (PRA) and serum aldosterone levels were also measured. In eight patients, uProt/uCreat was also assessed after 9 months and 12 months of SP treatment.

Results

After beginning SP therapy, all patients showed significant decrease in mean uProt/uCreat ratio (1.77?±?0.8 to 0.86?±?0.6; p?<?0.001) and mean urinary TGF-β1 levels (104?±?54 to 41?±?20 pg/mgCreatinine; p?<?0.01), beginning after 30 days of treatment and remaining stable throughout SP administration. PRA remain unchanged, and mean serum aldosterone increased from 105?±?72 pg/ml to 303?±?156 pg/ml (p?<?0.001). The only side effect was gynecomastia in an obese boy. After 1 year of therapy, mean uProt/uCreat remains low (0.82?±?0.48).

Conclusions

Addition of SP to ACE-I treatment with or without angiotensin II receptor blokers (ARB) significantly reduced proteinuria. This was mediated by decreased urinary TGF-β1 levels and not associated with major side effects.     

Successful treatment of combination therapy using an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker in a patient with IgA nephropathy

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.     

Combined converting enzyme inhibition and angiotensin receptor blockade reduce proteinuria greater than converting enzyme inhibition alone: insights into mechanism

Patients with various renal diseases receiving an angiotensin-converting enzyme inhibitor (CEI) were enrolled in a protocol to determine whether adding an angiotensin type 1 receptor blocker (ARB) reduces urinary protein excretion (UPE). All patients had significant proteinuria (range 517-8,562 mg/24 h) despite administration of CEI for at least 4 weeks. Following baseline measurements, losartan (50 mg/d) was started and testing was repeated at 1 month. Compared with CEI alone, combined CEI plus ARB reduced UPE by 45 +/- 8% (p < 0.005). Compared with CEI alone, CEI + ARB lowered UPE in each patient independent of baseline protein excretion or renal diagnosis. Reduction in proteinuria occurred independent of changes in mean arterial blood pressure (MAP), suggesting that the mechanism involved local changes in glomerular dynamics. If renal angiotensin II (ANG II) formation occurred despite CEI, the ANG II formed would suppress plasma renin activity (PRA), and adding an ARB would cause PRA to rise. In 7 of 10 subjects, addition of ARB to CEI increased PRA (p < 0.03) suggesting that intrarenal ANG II formation occurred in CEI-treated subjects. As a second marker of ANG II tissue activity, we measured the effects adding ARB on plasma aldosterone (ALDO). In 9 of 10 subjects, ALDO was acutely lowered (p < 0.009) suggesting that ANG II levels were incompletely blocked by CEI. We conclude that: combined CEI and ARB reduces UPE greater than CEI alone; reduction in proteinuria is independent of changes in MAP or renal diagnosis; and the additive effects of CEI and ARB are due at least in part to greater inhibition ofANG II action at the tissue level in the kidneys and adrenal glomerulosa.     

Proteinuria after conversion to sirolimus in kidney transplant recipients: impact of pre‐existing proteinuria,graft function,and angiotensin‐converting enzyme inhibitors/angiotensin‐receptor antagonists

Marx C, Busch M, Ott U, Gerth J, Wolf G. Proteinuria after conversion to sirolimus in kidney transplant recipients: impact of pre‐existing proteinuria, graft function, and angiotensin‐converting enzyme inhibitors/angiotensin‐receptor antagonists.
Clin Transplant 2009 DOI:10.1111/j.1399‐0012.2009.01142.x.
© 2009 John Wiley & Sons A/S. Abstract: Background: Proteinuria is a known side effect of therapy with sirolimus. The effect of angiotensin‐converting enzyme inhibitors or angiotensin‐receptor blockers (ACEI/ARB ) on sirolimus‐associated proteinuria has not yet been assessed. Patients and methods: A retrospective cohort study of renal transplant patients treated with sirolimus (n = 55) was performed. Results: Of 55 patients, 24 (44%) had no proteinuria (<0.15 g/d) prior to conversion. Of 24 patients, 11 (46%) showed de novo proteinuria >0.15 g/d after 12 months, only 2 developed proteinuria > 1 g/d. The total number of proteinuria >1 g/d after 12 months including patients with pre‐existing proteinuria >1 g/d (n = 3) was seven of 55 patients (13%). Multivariate regression analysis revealed pre‐existing proteinuria > 0.15 g/d and reduced glomerular filtration rate as independent predictors for the development of proteinuria after conversion to sirolimus. Conclusion: Reduced glomerular filtration rate and pre‐existing proteinuria but not therapy with ACEI/ARB are independent predictors for proteinuria after conversion to sirolimus. Treatment with ACEI/ARB did not reduce pre‐existing proteinuria after conversion except in single cases with severe proteinuria.     

Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?

BACKGROUND: While interruption of angiotensin synthesis and angiotensin blockade are well know to reduce proteinuria and preserve renal function in patients with diabetic glomerulosclerosis, many patients still have significant proteinuria after having reached maximal doses of those medications. We chose to examine the effect of the addition of pentoxifylline to the therapeutic regimen of patients with significant proteinuria and chronic renal insufficiency who had reached maximal does of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB), on the reduction of proteinuria and the preservation of renal function. METHODS: Seven male patients with diabetic glomerulosclerosis with proteinuria of at least 1.5 g/24 hours and a creatinine clearance of at least 15 ml/min despite maximal doses of an ACEI and an ARB for over 12 months were treated with pentoxifylline adjusted for creatinine clearance. They were then compared with 7 similar patients matched for age, duration of medications, proteinuria, creatinine clearance and mean arterial pressure. The groups were compared for any significant differences on at baseline and at 12 months. RESULTS: Although proteinuria decreased in the pentoxifylline group (5.657 +/- 3.5227 to 3.799 +/- 3.647 g/24 hours) there was no significant difference from the control group (4.743 +/- 2.320 to 4.986 +/- 2.941 g/24 hours). Similarly both groups lost creatinine clearance (41.0 +/- 27.44 to 29.33 +/- 22.21 ml/min with pentoxifylline and 45.57 +/- 21.854 to 27.33 +/- 27.105 ml/min in controls), but there was no significant difference in either clearance or mean arterial pressure. CONCLUSION: Although there was a trend toward the reduction of proteinuria, we found no statistical benefit in proteinuria reduction or preservation of renal function by the addition of pentoxifylline to maximal doses of ACEIs and ARBs.     

Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy

Abstract

Objective: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin–angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN. Methods: Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI?+?ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI). Results: In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups. Conclusion: Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.     

Mineralocorticoid Receptor Antagonist for Renal Protection

The renin–angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular and renal diseases. In chronic kidney disease (CKD), blockade of RAS by angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) has been shown to reduce proteinuria and retard the progression of renal function deterioration. However, aldosterone, another key hormone of the RAS, is not directly targeted by ACEI or ARB. Hyperaldosteronism, apart from promoting sodium and fluid retention, causes inflammation and fibrosis in the heart and kidney. Studies have shown that although plasma aldosterone level shows an initial decrease following ACEI or ARB treatment, it returns to pretreatment level or even increases paradoxically after prolonged treatment. This “aldosterone breakthrough” forms the basis of adding mineralocorticoid receptor (MR) antagonist on top of ACEI or ARB for renal protection. New insights into the pathophysiological role of aldosterone in CKD further expands its potential indications, and there was a growing body of evidence in the past 10 years, which showed a substantial antiproteinuric effect and possibly a considerable renoprotective effect of MR antagonist. Since aldosterone does not act on the efferent glomerular arteriole and has no effect on intraglomerular hemodynamics, the very fact that MR antagonist ameliorates proteinuria sheds light on the physiology of glomerular permeability barrier. This review summarizes the data regarding the theoretical benefit as well as clinical use of MR antagonist in renal diseases.     

Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome

The effects of angiotensin converting enzyme inhibitors (ACEI) on proteinuria, renal function, and serum proteins were evaluated in six children with steroid-resistant nephrotic syndrome and proteinuria of 3–15 g/24h (277±47 mg/m² per hour). Following ACEI, proteinuria decreased from 7,408±2,385 (mean±SEM) to 3,746±1,395 mg/24 h (P<0.05). Creatinine clearance was 87.8±22.6 before and 96.4±23.6 ml/min per 1.73 m² after ACEI. In two patients, inulin and para-aminohippuric acid clearances were normal before and after ACEI, together with parallel reductions of urine protein of 50% and 46%. Clearance of total protein was reduced by 56% following ACEI, compared with reduction in the clearance of gamma globulin by 58% and albumin by 39.5%. No significant change was seen in blood pressure, serum albumin, or total protein following ACEI. After ACEI, diuretic doses were able to be reduced or eliminated in three patients. Reduction of proteinuria was sustained during a followup period of 11–20 months in three patients. ACEI may be of benefit in the clinical management of children with steroidresistant nephrotic syndromes, allowing reduction in diuretic requirements.     

Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients

The aim of this work was to study the effect of early administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I receptors blockers (ARB) on renal function and proteinuria in renal transplant recipients with good, stable renal function and mild proteinuria. Twenty four patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood pressure, and serum lipid levels. Twenty-eight patients who never received ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003); UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8 +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0. Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects at 2 years of the study. The values of other parameters did not show significant differences between the two groups. In conclusion, this study suggested that ACEI/ARB have renoprotective effects, when used in patients with good stable renal function and mild proteinuria. These drugs may play a role to prevent chronic allograft nephropathy.     

Incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers alone,or combined with angiotensin?converting enzyme inhibitors in patients with non?diabetic nephropathy

Objective To investigate the incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin II receptor blockers (ARB) alone, or combined with angiotensin?converting enzyme inhibitors（ACEI） in Chinese patients with non?diabetic nephropathy. Methods A total of 144 patients with non?diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB for a mean follow?up period of 12 months. Aldosterone breakthrough was determined according to the change of plasma aldosterone concentration before and after treatment during 6?month and 12?month ACEI/ARB treatment. Results In 6 months, aldosterone breakthrough occurred in 21 patients, corresponding to 14.58%, while in 12 months, occurred in 39 patients, corresponding to 27.08%. Although the overall urinary protein excretion (UPE) decreased after treatment in both groups (P<0.05), non?breakthrough group had a more remarkable reduction in UPE (P<0.05). Univariate Logistic regression demonstrated that risk factors of aldosterone breakthrough included pre?treatment values of UPE (OR=3.643, P=0.073) and eGFR（OR=0.980, P=0.025）. Multivariate Logistic model revealed pre?treatment values of eGFR was positively associated with aldosterone breakthrough (OR=0.980, P=0.025). Conclusions The incidence of the aldosterone breakthrough increases with duration of treatment. The patients with aldosterone breathrough have higher level of UPE, and enhanced decline in eGFR. Pre?treatment value of eGFR is independent risk factor of aldosterone breakthrough.     

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.