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.     

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。     

糖尿病肾内动脉血流动力学改变的研究

目的：观察糖尿病肾病不同时期肾内分级动脉血流动力学的改变。方法：用脉冲多普勒方法分别测量正常对照组、糖尿病正常蛋白尿阶段，隐匿性肾病．临床糖尿病肾病肾功能代偿期及糖尿病肾病肾功失代偿期各组肾内分级动脉Vmax、Vmin、TAMX、PI、RI血流参数．并与对照组比较。结果：糖尿病不同时期Vmax均增高．与正常对照组有显著性差异；Vmin随着病程的发展．逐渐减低；PI、RI随病情的进展逐渐增高．尤以糖尿病肾病肾功能代偿期及肾病肾功失代偿期明显。结论：多普勒超声是一种简便、直观、快速非创伤性检查糖尿病血流动力学改变的方法．通过对肾内分级动脉血流参数的观察．尤其是PI、RI的变化，判断糖尿病肾损害的程度。     

循环内皮细胞水平与糖尿病肾病的相关性及银杏达莫的干预作用

目的:探讨外周血循环内皮细胞(CEC)和糖尿病肾病(DN)的相关性,以及银杏达莫注射液在DN防治中的可能作用。方法:检测65例2型糖尿病患者24h尿白蛋白排泄率(UAER)及CEC数,分析两者的相关性。将UAER为30~300mg·d-1的45例患者随机分为两组,常规治疗组22例,进行常规降血糖、控制血压等治疗;银杏达莫治疗组23例,在常规治疗基础上静脉滴注银杏达莫注射液2周。比较两组治疗前后血糖、血压、UAER及CEC水平的变化。结果:单纯糖尿病(SDM)组和早期糖尿病肾病(EDN)组的外周血CEC水平比对照组(NC)显著性升高,并呈逐渐增高的趋势(P<0.01)。UAER与收缩压(SBP)、外周血CEC水平呈正相关(P<0.01)。EDN组中,银杏达莫治疗后UAER及CEC明显降低(P<0.01);而常规治疗组无明显变化。线性多元逐步回归分析表明,银杏达莫治疗后UAER的改变与CEC数的变化成正相关(P<0.01)。结论:血管内皮细胞(VEC)损伤在DN发生发展中起重要作用,银杏达莫对VEC的保护作用可能是其延缓DN发展的重要机制。     

Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome

We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed. Southwest Pediatric Nephrology Study Group (Central Office, Baylor University Medical Center at Dallas, Tex., USA). Director, Ronald J. Hogg; Associate Directors, Fred G. Silva and F. Bruder Stapleton; Statistician, Joan S. Reisch; Administrative Assistant, Kaye Green. Participating Centers—Baylor College of Medicine, Houston, Tex.: Phillip L. Berry, L. Leighton Hill, Sami A, Sanjad, Edith Hawkins; Baylor University Medical Center, Dallas, Tex.: Ronald J. Hogg, Kaye Green; Tulane University Medical Center, New Orleans, La.: Frank Boineau, John E. Lewy, Radhakrishna Baliga, Patrick Walker; University of Arkansas, Little Rock, Ark.: Watson Arnold, Eileen Ellis, Edward Uthman; University of Colorado Health Science Center, Denver, Colo.: Gary M. Lum, Wiliam Hammond; University of Oklahoma Medical Center, Oklahoma City, Okla.: James Wenzl, James Matson, Geoffrey Altshuler, Sarah Johnson; University of Tennessee, Memphis, Tenn.: F. Bruder Stapleton, Shane Roy, III, Robert J. Wyatt, Charles McKay, William Murphy; University of Texas Health Science Center at Dallas, Tex.: Billy S. Arant Jr, Michel Baum, Fred G. Silva, Arthur Weinberg, Craig Argyle, Joseph Rutledge, Ed Eigenbrodt; University of Texas Medical School, Houston, Tex.: Susan B. Conley, Jacques Lemine, Ron Portman, Ann Ince, Regina Verani; University of Texas Health Science Center at San Antonio, Tex.: Michael Foulds, Sudesh Makker, Kanwal Kher, Melanie Sweet, Victor Saldivar, Fermin Tio; University of Texas Medical Branch, Galveston, Tex.: Ben H. Brouhard, Alok Kalia, Luther B. Travis, Lisa Hollander, Tito Cavallo, Srinivasan Rajaraman; University of Utah Medical Center, Salt Lake City; Utah: Eileen Brewer, Richard Siegler, Elizabeth Hammond, Theodore Pysher. Note that this list reflects the investigators' addresses and positions during the period of this study and not necessarily their current situations.