缬沙坦治疗糖尿病肾病的疗效观察

目的:观察血管紧张素Ⅱ,Ⅰ型受体拮抗剂(AT1Ra)缬沙坦(Valsartan)对伴大量白蛋白尿的临床糖尿病肾病的治疗作用。方法:32例2型糖尿病患者,24h尿白蛋白排泄率(24hUAER)>200μg/min,均伴高血压,维持原糖尿病治疗不变,分组比较应用缬沙坦(80mg/d)或贝那普利(10mg/d)治疗8周前后平均动脉压(MAP)、24hUAER、HbA1c、尿酸(UA)等指标的变化。结果:缬沙坦治疗组和贝那普利治疗组24hUAER分别由703.2±987.9μg/min降至664.2±970.6μg/min(P<0.01)和由778.6±1005.0降至734.9±996.0μg/min(P<0.01)。二者疗效相似,且均与血压变化不相关。结论:AT1Ra缬沙坦可以降低临床糖尿病肾病的蛋白尿,其肾脏保护作用除了与降血压有关,还有不依赖降压效应的其他机制。     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

激素间歇冲击及小剂量维持治疗IgA肾病的随机对照研究

目的:探讨激素间歇冲击及小剂量维持与血管紧张素转换酶抑制剂治疗中度蛋白尿IgA肾病的疗效及其影响因素。方法:47例IgA肾病患者随机分为实验组和对照组。对照组(21例)给予ACEI药物治疗,实验组(26例)在此基础上口服泼尼松0.5mg/kg,隔日给药,治疗12个月,并在治疗的第1、3、5个月初分别给予甲基泼尼松龙0.5g/d,冲击3d。对肾脏病理改变进行WHO分级并对各种病变进行半定量分析。结果:两组间在性别、年龄、临床及病理资料间无统计学差异。平均随访14个月后,实验组尿蛋白完全缓解8例(30.8%),部分缓解14例(53.8%),无缓解4例(15.4%);而对照组分别为4例(19.1%),3例(23.8%),12例(57.1%),有统计学差异(P<0.01)。治疗前后,实验组血肌酐分别为(89.9±30.3)μmol/L及(88.2±32.8)μmol/L;对照组分别为(89.5±37.9)μmol/L及(104.0±49.7)μmol/L,但两者比较均无统计学意义(P>0.05)。多因素分析显示疗效与肾小球硬化率及肾小管间质病变呈负相关。结论:激素间歇冲击及小剂量维持治疗能显著减少蛋白尿,维持肾功能稳定。影响疗效的主要因素为肾小球硬化率及肾小管间质病变程度。     

The shape of stress: the use of frequent sampling to measure temporal variation in S‐IgA levels during acute stress

Previous studies have indicated that statistically significant increases in Secretory immunoglobulin A (S‐IgA) can be achieved in as little as 5min as a result of mental stress. However, the temporal resolution of these changes is low and therefore the rate and pattern of changes during the stress task and during subsequent recovery is unclear. A within‐subjects design was used to examine levels of S‐IgA before, during and after a short (8 min) mental stress task. S‐IgA was measured from saliva samples obtained every 2 min during the entire 30‐min session. Significant increases in S‐IgA concentration were observed as early as the task instruction period, with additional increases during the stress task itself. The data also show a rapid recovery of S‐IgA, with a return to baseline levels within 6 min. Results suggest that S‐IgA changes can occur very rapidly and that the observed increases are short‐lived. Copyright © 2007 John Wiley & Sons, Ltd.     

氟伐他汀对糖尿病肾病大鼠足细胞分布及排泄的影响

目的探讨氟伐他汀对DN大鼠足细胞分布及排泄的影响。方法将大鼠分为3组：对照组、DN模型组、氟伐他汀治疗组。腹腔注射链脲菌素（STZ）诱导DN大鼠模型。实验10周末测24小时尿蛋白定量（TP）、血清总胆固醇（TC），间接免疫荧光法检测尿沉渣足细胞特异性标志蛋白podocalyxin（PCX）以检测尿液足细胞（UPC）水平；免疫荧光染色观察肾小球上皮细胞蛋白-1（GLEPP1）的分布。结果DN模型组UPC、TP、TC较对照组均明显升高；氟伐他汀治疗组TC、UPC及TP较DN模型组均降低；对照组GLEPP1正常、DN模型组呈节段性明显缺失、氟伐他汀治疗组缺失较轻。UPC与TP呈正相关，与TC无显著相关性。结论尿液中脱落足细胞检测可作为判断DN病情活动性的标志之一。氟伐他汀可减轻DN大鼠尿蛋白、降低胆固醇、减少足细胞脱落及排泄。     

儿童无症状尿检异常IgA肾病的临床病理和预后分析

目的 探讨儿童无症状尿检异常的IgA肾病的临床病理特征和预后。 方法 对54例IgA肾病儿童的临床和病理特征进行分析。根据起病时有无临床症状分为无症状尿检异常组和有症状肾炎组。组织病理学分级参照Lee氏和Katafuchi氏半定量积分法。 结果 无症状尿检异常组18例，有症状肾炎组36例。有症状肾炎组尿蛋白量（24 h）明显高于无症状尿检异常组[（2.3±2.2） g比（0.4±0.3） g，P < 0.05]。无症状尿检异常的IgA肾病儿童表现为镜下血尿者，87％有尿微量白蛋白增高。无症状尿检异常IgA肾病患儿病理表现以Lee 氏Ⅰ~Ⅱ级为主，2例表现为Lee氏Ⅳ~Ⅴ级和 5例发生Katafuchi Ⅱ~Ⅲ级肾小管间质病变。有症状肾炎组Lee氏病理分级以Ⅱ~Ⅲ级为主，两者病理分级分布差异无统计学意义（P > 0.05）。全组患儿平均随访（26.9±8.8）月后，1例病理为Lee 氏Ⅴ级患儿进入终末期肾衰竭，其余患儿Scr均无升高1倍以上。 结论 无症状尿检异常的儿童IgA肾病虽临床症状轻微，但可出现病理损害严重的病例，并影响其预后。