安体舒通降低早期糖尿病肾病患者尿蛋白的疗效观察

目的：探索安体舒通对于降低早期糖尿病肾病患者尿蛋白及肾功能保护的作用。方法：将45例伴有持续性微量蛋白尿的2型糖尿病患者纳入研究,接受3个月的安体舒通治疗（20mg,每日2次）。其中30例已经接受半年以上血管紧张素转化酶抑制剂（ACEI）/血管紧张素Ⅱ受体拮抗剂（ARB）治疗的患者组成联合治疗组（安体舒通＋ACEI/ARB）;15例未接受ACEI/ARB治疗的患者组成单用安体舒通治疗组,对治疗3个月前后的尿蛋白定量、肾小球滤过率、血液生化、血压、体重指数等情况进行对比。结果：经过3月的治疗,联合治疗组患者尿蛋白显著下降,伴有血钾上升（在安全范围内,均〈5.5mEq/L）,肾小球滤过率无显著变化。单用安体舒通治疗组患者的尿蛋白下降差异无统计学意义。结论：安体舒通,与ACEI/ARB合用,可有效降低早期糖尿病肾病患者的蛋白尿,并且耐受性良好,安全性较好。     

雷公藤多苷联合舒洛地特治疗2型糖尿病肾病Ⅳ期的疗效观察

目的：观察雷公藤多苷联合舒洛地特治疗2型糖尿病肾病Ⅳ期的疗效。方法：2型糖尿病肾病Ⅳ期病人60例,随机分为对照组和实验组各30例。对照组给与糖尿病肾病常规治疗及雷公藤治疗,实验组在对照组用药基础上加用舒洛地特,8周后测定两组病人24h尿蛋白定量、APTT、Fbg-c、TC、TG、LDL-C。结果：对照组与实验组治疗8周后24h尿蛋白定量均较治疗前有所下降（P0.05）;实验组治疗后APTT延长,Fbg-c下调,与治疗前相比差异有统计学意义（P〈0.01）;两组治疗后TC、TG、LDL-C均显著下降（P〈0.01）;实验组与对照组对比下降更明显差异有统计学意义（P〈0.01）。结论：雷公藤多苷联合舒洛地特治疗2型糖尿病肾病Ⅳ期较单独应用雷公藤多苷疗效更佳。     

舒洛地特治疗糖尿病肾病的系统评价

目的:系统评价舒洛地特治疗糖尿病肾病的疗效和安全性。方法:全面检索所有关于舒洛地特治疗糖尿病肾病的临床随机对照研究。比较舒洛地特与安慰剂、不予治疗或者其他药物对糖尿病肾病的疗效和安全性。两位作者独立提取数据,并评价纳入研究的质量。采用RevMan5.1对纳入研究的相关指标进行统计分析。对不良反应进行搜集和分析。对非连续变量和连续变量分别用RR值(相对危险度)和WMD值(加权均数差)表示,并计算其95%可信区间。结果:最终纳入10个随机对照试验。共有患者751例,其中468例在舒洛地特组,283例在对照组。与安慰剂或者不做治疗组或ACEI/ARB组相比较,舒洛地特可以降低DKD患者尿蛋白排泄率、尿蛋白、胆固醇、三酰甘油、纤维蛋白原、肌酐清除率、抗凝血酶Ⅲ;但对于患者血压、空腹血糖、糖化血红蛋白、肌酐、尿素氮无明显作用。在报道的皮疹、腹泻、腰疼、肌肉关节症状等病例方面治疗组报道的例数多于对照组,但差异无统计学意义。结论:舒洛地特能改善影响DKD患者预后的相关指标。但鉴于纳入的研究数量和质量的局限性,本文结论应审慎解读。     

25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性研究

目的 探讨25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性。方法 收集937例未接受维生素D补充治疗的2型糖尿病患者,测定各临床指标以分析糖尿病肾病的相关因素。结果 与正常尿微量白蛋白组患者相比,微量或大量尿白蛋白组患者的25-(OH)VD 水平较低且具有显著统计学差异。相关性分析显示,用性别和BMI作为校正指数,年龄、糖尿病病程、高血压病程、收缩压、糖化血红蛋白、肌酐、尿素氮与尿微量白蛋白呈正相关,而25-(OH)VD 水平与尿微量白蛋白呈负相关。结论 25-(OH)VD 水平与2型糖尿病患者的尿微量白蛋白呈显著负相关。     

益气活血法治疗糖尿病肾病的meta分析

目的：评价口服益气活血中药在治疗糖尿病肾病（DN） 蛋白尿方面的疗效.方法：检索中国期刊全文数据库（CNKI,2008年-2013年）,维普中文科技期刊全文数据库（2008年-2013年）,中国生物医学文献数据库（CBM,2008年-2013年）,万方中华医学会数字化期刊（2008年-2013年）,收集口服益气活血中药与单用ACEI/ ARB,或者合用ACEI/ ARB比较,治疗糖尿病肾病的随机对照试验（RCT）.两名评价员独立评价纳入RCT的方法学质量,采用Revman4.2软件做Meta 分析.结果：纳入20篇中文RCT.3篇论文被评为B 级,17篇论文被评为C 级.5个试验采用了随机数字表法.Meta 分析结果显示：益气活血中药临床总有效率明显高于对照组（RR=1.30,95%CI（1.20,1.40）;与常规基础治疗相比,益气活血中药可明显降低尿微量蛋白排泄率（WMD=30.38,95%CI（23.04,37.71）,P〈0.000 01）;益气活血中药联合ACEI或ARB与单用ACEI或ARB比较,在降低糖尿病肾病患者尿微量蛋白排泄率无显著优势[WMD= 49.63,95%CI（-8.30,107.67）,P=0.09];益气活血中药联合ACEI/ARB与单用ACEI/ARB比较能显著降低24 h尿微量白蛋白[SMD=-1.11,95%CI（-1.75,-0.47）,P〈0.000 7];益气活血中药可明显降低24 h尿蛋白定量水平[SMD=-1.62,95%CI（-3.08,-0.16）,P=0.03〈.05].结论：益气活血中药可以减少糖尿病肾病蛋白尿.但是,研究文献的质量有待提高,该Meta 分析的可靠性受到影响.故益气活血中药在降低DN 尿蛋白方面的疗效仍需深入研究.     

血清镁水平与非胰岛素依赖型糖尿病肾病的关系

目的:探讨非胰岛素依赖型糖尿病患者血清镁水平和处发以及明显糖尿病肾病的关系.方法:以2型糖尿病患者为研究对象,根据尿白蛋白排泄值分为3组:无蛋白尿组,尿白蛋白排泄值＜30 mg/d;微量白蛋白尿组,30 mg/d＜尿白蛋白排泄值＜300 mg/d;临床蛋白尿组,尿白蛋白排泄值＞300 mg/d.并以同期健康成人16例作为对照组.检测身高、体重、血压、空腹血糖、 血清肌酐、胆固醇、甘油三酯、糖化血红蛋白、血清镁及尿白蛋白排泄值.并对数据进行统计学分析.结果:根据尿白蛋白排泄值,共有22例患者进入无白蛋白尿组;22例进入微量白蛋白尿组;20例进入临床蛋白尿组.与正常对照组比较,糖尿病患者的血清镁水平明显降低,并随着白蛋白尿程度的加重而更加明显.同时,空腹血糖、糖化血红蛋白及甘油三酯水平随着白蛋白尿程度的加重而明显升高.相关分析显示,对于出现糖尿病肾病的患者,血清镁水平与糖化血红蛋白及甘油三酯水平呈明显负相关,多元线性回归分析显示,血清镁的降低与糖化血红蛋白及甘油三酯的升高有密切关系.结论:2型糖尿病患者存在明显的低镁血症,并且随着糖尿病肾病的加重而明显降低.出现低镁血症的原因可能是血糖控制不理想及白蛋白尿对肾小管的持续损害所致.     

奥美沙坦延迟或预防2型糖尿病患者的微量蛋白尿

糖尿病肾病3期或者4期的患者肾素-血管紧张素系统过度激活,会出现微量到大量的蛋白尿,ACEI或ARB可减缓GFR恶化的进程,减少白蛋白的排泄。ACEI可延缓那些伴有高血压、糖尿病、蛋白尿正常、肾功能正常的患者微量蛋白尿出现的时间,但是ARB在糖尿病患者中的早期使用是否有同样的作用尚不知道。     

黄芩素对糖尿病肾病患者外周血NF-κB、VEGF、TGF-β_1的影响

目的:探讨黄芩素对糖尿病肾病患者外周血核因子-κB(NF-κB)、血管内皮生长因子(VEGF)、转化生长因子β_1(TGF-β_1)水平的影响及其临床疗效观察。方法:随机筛查我院就诊的糖尿病肾病患者100例,进行3个月基础治疗,分为糖尿病肾病微量蛋白尿组50例(尿白蛋白/尿肌酐30～300 mg/g),糖尿病肾病大量蛋白尿组50例(尿白蛋白/尿肌酐大于300 mg/g),予以黄芩素铝胶囊1. 2 g每日三次治疗3个月。比较糖尿病肾病患者治疗前后血清肌酐、血糖、糖化血红蛋白、尿白蛋白/尿肌酐和外周血单个核细胞NF-κBP65、血清TGF-β_1及VEGF变化。结果:与正常组比较,不同蛋白尿水平的糖尿病肾病患者及糖尿病患者外周血NF-κBp65均有明显激活(P 0. 05),与ACR成正相关;糖尿病肾病组治疗后与治疗前比较,黄芩素可抑制NF-κBP65、TGF-β_1、VEGF表达,减少尿白蛋白排泄(P 0. 05)。通过糖尿病肾病微量蛋白尿组及大量蛋白尿组治疗前后比较,黄芩素明显减少糖尿病肾病微量蛋白尿组尿白蛋白排泄。结论:黄芩素可抑制糖尿病肾病患者外周血NF-κB活化及降低VEGF、TGF-β_1水平,减少尿白蛋白排泄延缓糖尿病肾病进展,对早期糖尿病肾病进展延缓明显。     

舒洛地特对糖尿病高血压大鼠足细胞podocalyxin表达的影响

目的 研究舒洛地特对糖尿病高血压大鼠的肾脏保护作用和足细胞podocalyxin（PCX）表达的影响。 方法 链脲佐菌素（STZ）注射后,醋酸脱氧皮质酮（DOCA）+盐建立糖尿病高血压大鼠模型。设对照组（CTL组）、模型组（STZ+DOCA组）、舒洛地特治疗组（GAG组）和舒洛地特+替米沙坦治疗组（GAG+ARB组）,每组各6只大鼠。于建模后0、2、4、6和8周测尾动脉压、尿白蛋白和8周末尿N-乙酰-β-葡萄糖苷酶（NAG）。8周末取血检测胰岛素、血肌酐（Scr）、胆固醇（TC）、三酰甘油 （TG）、Na+、K+。HE、PAS染色观察病理改变和肾小球正切面足细胞计数。免疫组织化学检测podocalyxin在肾小球表达和分布。RT-PCR和Western印迹法检测podocalyxin mRNA和蛋白表达。 结果 （1）GAG+ARB组4周末血压显著低于STZ+DOCA组和GAG组（P < 0.05）。GAG组和GAG+ARB组TG、TC和胰岛素与STZ+DOCA组差异无统计学意义。（2）6周末GAG+ARB组尿白蛋白量显著低于STZ+DOCA组 [（52.9±7.6） mg/24 h比（102.2±6.9） mg/24 h,P < 0.05];8周末GAG组和GAG+ARB组尿白蛋白量均显著低于STZ+DOCA组（P < 0.05）,而GAG+ARB组尿白蛋白量显著低于GAG组[（33.8±6.8） mg/24 h比(85.2±8.7) mg/24 h,P < 0.05]。GAG+ARB组和GAG组尿NAG均显著低于STZ+DOCA组（P < 0.05）。（3）GAG组和GAG+ARB组肾小球硬化指数（GSI）和间质纤维化指数（IF）均显著低于STZ+DOCA组（P < 0.05）,各组肾小球正切面足细胞数差异无统计学意义。（4）与STZ+DOCA组相比,GAG组PCX mRNA和蛋白表达显著增加,而GAG+ARB组PCX表达显著高于GAG组。 结论 舒洛地特可通过增加足细胞podocalyxin表达,减轻糖尿病高血压大鼠蛋白尿和病理损伤,与替米沙坦联用有叠加作用。     

低剂量雷米普利对2型糖尿病肾病患者尿蛋白的影响

目的:观察雷米普利(ramipril)对不同时期2型糖尿病肾病患者尿蛋白及肾功能的影响.方法:选择2型糖尿病肾病患者90例,年龄42岁～76岁.分为治疗组54例,对照组36例.两组患者均根据尿蛋白和肾功能的不同再分为早期肾病组、临床期肾功能正常组和临床期肾功能不全组.治疗组给予口服雷米普利(2.5 mg/d),连续应用12周.对照组不予上述治疗.结果:与对照组比较,治疗组患者尿总蛋白和尿白蛋白明显降低,其中2型糖尿病早期肾病组尿总蛋白由治疗前的(0.34±0.11)g/24 h下降到(0.24±0.09)g/24 h(P＜0.01),尿白蛋白由(199±50)g/24 h下降到(148±35)g/24 h(P＜0.01);临床期肾功能正常组尿总蛋白由治疗前的(2.15±1.01)g/24 h下降到(1.66±0.86)g/24 h(P＜0.01);临床期肾功能不全组尿总蛋白由治疗前的(1.93±0.91)g/24 h下降到(1.68±0.81)g/24 h(P＜0.05).结论:应用雷米普利对不同时期的2型糖尿病肾病患者均有减少尿蛋白的作用,且早期应用效果尤佳.     

Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria.

BACKGROUND: Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial. METHODS: A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization. RESULTS: The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed. CONCLUSION: Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.     

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.     

Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB.

BACKGROUND: Angiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus (DM). METHODS: After two weeks of streptozotocin-induced DM, rats received either no treatment, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for two weeks. At four weeks, renal expression of the p47phox component of NAD(P)H oxidase, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and nitrotyrosine were evaluated by Western blot and immunohistochemistry and related to plasma lipid peroxidation products (LPO), hydrogen peroxide production in the kidney and 24-hour protein excretion. RESULTS: Immunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO, renal hydrogen peroxide production and nitrotyrosine deposition. Expression of nNOS was unaltered. Treatment with either ACEI or ARB prevented all these findings and also prevented significant microalbuminuria. The treatments did not affect the elevated blood sugar, nor did DM or its treatment affect the blood pressure or the creatinine clearance. CONCLUSION: Early proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM.     

IgA肾病患者单核细胞趋化蛋白-1的变化及相关性研究

目的：探讨IgA肾病（IgAN）患者血液、尿液中单核细胞趋化蛋白-1（MCP-1）的含量变化及其临床意义。方法：将125例患者分为两组,即大量蛋白尿组和小量蛋白尿组,选取20例正常人为对照组。采用酶联免疫吸附法对实验组及对照组血液、尿液MCP-1的含量进行检测,同时测定患者的24h尿蛋白定量和肾功能。结果：IgAN患者尿液中MCP-1的含量明显增高,大量蛋白尿组高于小量蛋白尿组和对照组。而IgAN患者血液MCP-1的含量与对照组比较差异无统计学意义。结论：IgAN的发病与趋化因子MCP-1有关。     

Analysis of clinical and pathological features of HIV associated renal disease

Objective To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients. Methods This retrospective study included all HIV infected patients who underwent renal biopsy during the course of their clinical care at PUMC hospital from 2002 to 2012. The pathology and clinical information were abstracted from each patient’s clinical record. Results Eight HIV infected patients had biopsy confirmed renal disease. The commonest presentation was proteinuria in eight patients, and microscopic hematuria in six patients. Two patients had serum creatinine levels abnormal. Renal pathologies included IgA nephropathy in four patients, and lupus-like nephropathy, non-specific focal segmental glomerulosclerosis, membranous nephropathy and Henoch-Schonlein purpura nephritis in one patient each. All 8 patients received highly active antiretroviral treatment (HAART). Urinary protein was decreased significantly in one of them. Another was relieved with ACEI/ARB in addition to HAART. Corticosteroid was given to the other 6 patients. Among them, two got remission. one presented no reaction and was given cyclosporine. One, whose urinary protein didn't decrease with ACEI/ARB, received corticosteroid and needed further observation. One had continued aggravation of the renal disease. One case died of AIDS. One case companied with IgA nephropathy whose proteinuria recurrence was considered having association with tenofovir renal toxicity relieved after adjustment of HAART. Conclusions Classical HIVAN is uncommon in Chinese HIV infected population, a variety of other pathologies were seen in HIV infected patients, renal biopsy can help confirm the diagnosis. In HIV infected patients with evidence of nephropathy should be treated with HAART at diagnosis. Addition of prednisone should be considered if HAART alone does not result in improvement of renal disease.     

Urinary excretion of podocytes in patients with diabetic nephropathy.

BACKGROUND: Detection of podocytes in the urinary sediments of children with glomerulonephritis has been shown to indicate severe injury to the podocytes. The aim of the present study was to determine whether podocytes are present in the urine sediments of adult patients with diabetes with and without nephropathy and whether trandolapril is effective for podocyte injury. METHODS: Fifty diabetic patients (10 with normoalbuminuria, 15 with microalbuminuria, 15 with macroalbuminuria and 10 with chronic renal failure) and 10 healthy controls were studied. Urinary podocytes were examined by immunofluorescence using monoclonal antibodies against podocalyxin, which is present on the surface of podocytes. In addition, we studied plasma metalloproteinase (MMP)-9 concentrations in all patients. RESULTS: Urinary podocytes were absent in healthy controls, diabetic patients with normoalbuminuria and diabetic patients with chronic renal failure. Podocytes were detected in the urine of eight diabetic patients with microalbuminuria (53%) and of 12 patients with macroalbuminuria (80%). The number of podocytes in the urine of patients with macroalbuminuria was significantly greater than in patients with microalbuminuria (P:<0.01). However, there was no relationship between urinary albumin excretion and urinary podocytes. In addition, plasma MMP-9 concentrations were significantly correlated with the number of urinary podocytes (P:<0.01). Twelve diabetic patients with macroalbuminuria and eight patients with microalbuminuria who had urinary podocytes were treated with the angiotensin-converting enzyme inhibitor trandolapril. Urinary albumin excretion, the number of podocytes and plasma MMP-9 concentrations were reduced by the trandolapril treatment. CONCLUSIONS: Podocytes in the urine may be a useful marker of disease activity in diabetic nephropathy. Trandolapril may be effective for podocyte injury.     

Renal protection in diabetes: is it affected by glucose control or inhibition of the renin-angiotensin pathway?

BACKGROUND: Recent reports indicate increased risk of renal failure with long-term use of angiotensin-converting enzyme inhibitors (ACEI) in diabetes. End-stage renal disease (ESRD) in diabetes has increased despite ACEI and angiotensin receptor blocker (ARB) use. This study questions renal protection by ACEI or ARB. Our hypothesis is that uncontrolled hyperglycemia is central to diabetic ESRD while tight glucose control is renoprotective. Cultured endothelial cells show morphological damage that increases with duration of exposure to high glucose and is prevented by insulin and more so by a combination of insulin and heparin. METHODS: Findings from individual patients are compared to clinical trial results wherein ACEI or ARB was emphasized as the prime therapy to prevent progression of diabetic nephropathy to ESRD. Serum creatinine (Scr) changes were the main indicator of renoprotective effects in clinical trials. Creatinine clearance (Ccl), an important marker of glomerular filtration rate, was seldom reported. RESULTS: Our observations show that ACEI-treated patients develop progressive renal failure, whereas renal function remains stable with optimum glucose control. Clinical trials showed that reduction of proteinuria, with ACEI, reduces the risk of ESRD. Our studies show that reduction of proteinuria with use of ACEI or ARB parallels a reduction in Ccl, suggesting that a change in proteinuria is related to Ccl changes. Scr changes are small, giving a deceptive view of renal protection. CONCLUSIONS: Our observations find no evidence of renal protection with ACEI or ARB use in diabetes. Laboratory studies and clinical observations suggest that adequate glucose control is the key to renal protection in diabetes.     

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.     

Protective effect of paraoxonase 1 of high-density lipoprotein in type 2 diabetic patients with nephropathy

Aim:   Paraoxonase 1 (PON1) is an important antioxidative enzyme associated with high-density lipoproteins (HDL). Recent data suggest that HDL antioxidative ability may be altered in type 2 diabetic patients. The aim of this study was, therefore, to investigate whether HDL-PON1 activity and HDL antioxidative ability were related to the presence and severity of diabetic nephropathy.
Methods:   Sixty type 2 diabetic patients, who were subdivided into normoalbuminuria, microalbuminuria and macroalbuminuria, and 20 age- and sex-matched healthy controls were recruited. HDL was then isolated to measure PON1 activity, lipid peroxide and its ability in protecting low-density lipoprotein (LDL) from oxidation.
Results:   HDL-PON1 activity and HDL antioxidative ability in protecting LDL from oxidation was preserved in diabetic patients with normoalbuminuria, but significantly decreased in those with microalbuminuria or macroalbuminuria. HDL peroxide was comparable between healthy controls and normoalbuminuric patients, but significantly increased in those with microalbuminuria or macroalbuminuria. On multiple analyses, urinary protein was an independent negative determinant of HDL-PON1 activity, and HDL-PON1 activity was positively associated with HDL antioxidative ability, and negatively associated with HDL peroxide.
Conclusion:   HDL-PON1 activity is decreased in type 2 diabetic patients with incipient or overt nephropathy, which relates to the reduced HDL antioxidative ability in protecting LDL from oxidation and increased peroxide in HDL.     

How to predict nephropathy in type 1 diabetic patients

OBJECTIVE: Do exaggerated increases in blood pressure and albuminuria during exercise occur earlier than microalbuminuria and which type of test is most predictive of diabetic nephropathy? MATERIAL AND METHODS: A total of 33 insulin-dependent normoalbuminuric men (mean duration of diabetes 14 years; mean age 28 years) and 34 age-matched apparently healthy control subjects were studied. Urinary albumin excretion, heart rate and blood pressure were measured during fixed workload (150 W) and fixed heart rate (155 beats/min) tests. Mean follow-up time was 13.1 +/- 3.2 years. A urinary albumin level in early-morning urine persistently >30 mg/l was considered a sign of diabetic nephropathy. RESULTS: Sixteen patients reached the endpoints of the study. Eleven had developed microalbuminuria and five macroalbuminuria (persistent levels of urinary albumin >300 mg/l). Of the latter patients, two needed dialysis. Systolic blood pressure and albumin excretion during the fixed heart rate test were higher in diabetic patients who developed signs of nephropathy than in control subjects and diabetic subjects with persistent healthy kidneys. Such differences were not found in the fixed workload test. There were no differences in glycated haemoglobin, blood pressure levels or albumin excretion at baseline between the two diabetic groups. CONCLUSIONS: To predict the development of diabetic nephropathy it seems important to choose a fixed heart rate test. High levels of systolic blood pressure in such a test were associated with the development of micro- and macroalbuminuria.