Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus

Clinical Rheumatology - Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well...     

核素^99mTc—DTPA测定GFR与公式估算GFR的相关性研究

目的：探讨核素^99mTc—DTPA测定GFR与MDRD公式、简化MDRD公式估算GFR的相关性。方法：178例CKD患者，用核素^99mTc—DTPA测定GFR，同时测定血清肌酐、尿素氮和白蛋白，根据年龄和性别分别用MDRD和简化MDRD公式估算GFR。结果：核素^99mTc—DTPA测定的GFR与MDRD公式估算的GFR有显著性差异，P=0．0001，MDRD公式高估了GFR；核素^99mTc—DTPA测定的GFR与简化MDRD公式估算的GFR亦有显著性差异，P=0．0001，简化MDRD公式低估了GFR；MDRD公式估算的GFR与核素^99mTc—DTPA测定的GFR呈正相关，r=0．8292，P〈0．01；简化MDRD公式估算的GFR与核素^99mTc—DTPA测定的GFR值呈正相关，r=0．8277，P〈0．01。结论：MDRD公式、简化MDRD公式估算的GFR与核素^99mTc—DTPA测得的GFR有差异，需进一步校正后用于估算GFR。     

不同程度慢性肾功能不全患者血清醛固酮水平变化

目的:探讨慢性肾功能不全患者肾功能不同程度减退时血清醛固酮(Ald)水平的变化趋势及两者的相关性。方法:各种病因导致的慢性肾功能不全而未开始替代治疗的患者共42例按Cockcroft-Gault计算的内生肌酐清除率(Ccr)的不同分成三组,第1组Ccr≥60ml(min·1.73m2),第2组20ml/(min·1.73m2)≤Ccr<60ml/(min·1.73m2),第3组Ccr<20ml/(min·1.73m2)但未开始透析,比较三组患者的血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)和血清Ald浓度(SACs),并对Ccr和SACs两者行相关性分析;PRA、AngⅡ和SACs的检测用放射免疫分析。结果:第3组患者的SACs较第1、2组显著升高(P<0.01),第2组患者的SACs也较第1组患者显著升高(P<0.05)。Ccr与SACs呈高度负相关(r=-0.685,P<0.001)。结论:慢性肾功能不全的患者,随着Ccr下降,SACs有逐渐升高的趋势。     

糖尿病患者尿白蛋白排泄率与骨密度相关性研究

为探讨糖尿病患者尿白蛋白排泄率（AER）与骨密度（BMD）的相关性,测定了106例糖尿病患者和20例正常人（对照组）24小时AER,根据糖尿病患者AER分为Ⅰ组即正常蛋白尿组、Ⅱ组即微量白蛋白尿组、Ⅲ组即大量白蛋白尿组,并分别测定其L2～4椎体、股骨近端BMD。结果显示,除Ⅰ、Ⅱ组男性患者腰椎BMD与对照组无明显差异外,其余各组、各部位BMD与对照组相比均明显下降（P＜0.01）;男女糖尿病AER正常患者分别与同性别对照组相比,其BMD亦降低（P＜0.01）。糖尿病患者中,Ⅲ组BMD明显低于Ⅰ、Ⅱ组（P＜0.05）。提示糖尿病肾病患者BMD比正常人低,大量蛋白尿组BMD较其它组显著下降。     

实验性糖尿病系统和肾组织RAS活性的变化

目的检测实验性糖尿病不同时期系统和肾组织ＲＡＳ活性变化。方法ＳＴＺ－糖尿病大鼠随机分两组：糖尿病对照组（ＤＣ组）和Ｃａｐｔｏｐｒｉｌ治疗组（ＡＣＥＩＤ组）,均予胰岛素治疗以维持中度高血糖,另设正常组（ＮC组）。病程７、３０、９０ｄ时测系统和肾内肾素、ＡＣＥ活性和ＡＴＩＩ浓度。结果ＤＣ组在７、３０ｄ时ＰＲＡ正常,至９０ｄ下降;血浆和肾内ＡＴＩＩ、肾内ＴＲＡ及血清ＡＣＥ在７、３０、９０ｄ时均升高。整个实验中ＡＣＥ变化不明显。而ＡＣＥＩＤ组血浆ＡＴＩＩ、３０和９０ｄ肾内ＡＣＥ及３０ｄ肾内ＡＴＩＩ均明显下降,但９０ｄ肾内ＡＴＩＩ仍高于ＮＣ组。结论糖尿病早期系统和肾组织ＲＡＳ活性增加;长期ＡＣＥＩ治疗可能激活组织局部合成ＡＴＩＩ的旁路途径。     

Compared staining of the phospholipase A2 receptor in the glomeruli of Chinese adults and children with idiopathic membranous nephropathy

Background

The identification of the M-type phospholipase A2 receptor (PLA2R) is a breakthrough recognized as a major target for adults with idiopathic membranous nephropathy (IMN). However, the role PLA2R played in pediatric patients with IMN, particularly in Chinese, has yet to be determined.

THSD7A-associated membranous nephropathy in a patient with neurofibromatosis type 1

Target antigens in idiopathic membranous nephropathy (MN) include the phospholipase A2 receptor (PLA₂R), and in some cases, the thrombospondin type 1 domain-containing 7A (THSD7A). A notable phenomenon is the high rate of cancer (reported to be as high as 20%) in patients with THSD7A-associated MN. Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by NF1 gene mutation, and clinically characterized by multiple cutaneous neurofibromas and café-au-lait spots. In this article, we report a patient with NF1 who developed THSD7A-associated MN when the NF1 skin lesions deteriorated. The patient, a 62-year-old male, was referred to us for nephrotic syndrome for 6 months. Physical examination revealed multiple cutaneous nodules throughout the entire body, and the patient noted recent increase in the numbers of these skin lesions. Cutaneous nodules excisional biopsy suggested NF1 and Sanger sequencing using genomic DNA extracted from peripheral blood revealed a previously reported heterozygous frameshift NF1 mutation (c.1541_1542delAG, p. Gln514fs). Renal biopsy revealed MN and immunohistochemistry (IHC) showed enhanced staining of THSD7A as well as PLA₂R along the glomerular basement membrane whereas the serum level of THSD7A and PLA₂R were both within normal range. The neurofibroma tissues were positive for THSD7A but not for PLA₂R on IHC. The patient did not respond to 6-month treatment with glucocorticosteroid and cyclophosphamide. In this exceptional case, strong positive staining of THSD7A in both skin and renal biopsy samples, together with the temporal association between nephrotic syndrome and skin lesions and lack of treatment response, suggested the possibility that MN could be the result of immune response to THSD7A in NF1. This report may improve understanding of the mechanistic link between MN and cancer.     

Aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle

Aldosterone increases cation transport and contractility of vascular smooth muscle, but the specific transporter involved and how it is linked to smooth muscle tone is unknown. Because the Na-K-2Cl cotransporter (NKCC1) contributes to vascular smooth muscle contraction and is regulated by vasoactive compounds, we sought to determine whether this transporter is a target of aldosterone in rat aorta. Treatment of adrenalectomized rats with aldosterone for 7 days resulted in a 63% increase in NKCC1 activity as measured by bumetanide-sensitive efflux of 86Rb+. Treatment of normal aortas in culture with aldosterone for 3 and 7 days resulted in 29% and 47% increases in NKCC1 activity, respectively. Aldosterone had no acute effect on 86Rb+ efflux. Stimulation of NKCC1 was blocked by spironolactone, a mineralocorticoid receptor antagonist, but not by RU38486, a glucocorticoid receptor antagonist. Aldosterone did not augment the stimulation of NKCC1 by phenylephrine and did not increase NKCC1 mRNA as determined by real-time polymerase chain reaction. We conclude that aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle through classic mineralocorticoid receptors but not through changes in the abundance of NKCC1 mRNA. This could account for the increase in Na+, K+, and Cl- fluxes previously observed in vascular smooth muscle from mineralocorticoid-treated animals and may contribute to increased vascular tone.     

肾小球系膜细胞三维立体培养方法的构建

建立一种肾小球系膜细胞三维立体培养系统，该系统可以模拟肾小球系膜细胞在肾小球系膜区的生长环境，并证实在三维立体培养系统中．肾小球系膜细胞在24、48和72h的增殖作用比传统贴壁培养时明显缓慢。     

Efficacy of low-dose leflunomide in lupus nephritis: A multi-center prospective study

Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN). Methods A prospective, multicenter, randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015. Patients were randomized to two groups. Oral leflunomide or intravenous cyclophosphamide was given to patients in each group. Both groups received a tapering course of oral prednisone therapy. All patients were followed up for 24 weeks. The blood biochemistry, urine index, clinical curative effect and adverse reaction were recorded and analyzed statistically. Results A total of 100 patients were enrolled in this clinical trial, including 48 patients in leflunomide group and 52 patients in cyclophosphamide group. After 24 weeks, the overall response rate was 79% (95%CI 67%-90%) in the leflunomide group and 69% (95%CI 56%-82%) in the cyclophosphamide group. 23% (95%CI 11%-35%) of patients in leflunomide group showed complete remission compared with 27% (95%CI 24%-30%) in cyclophosphamide group (P=0.35). The levels of 24-hr urine protein excretion, SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment. And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment. There was also no significant difference in changes of 24-hr urine protein excretion, SLEDAI score, anti-dsDNA antibody titers, serum albumin and complement C3 levels after treatment between two groups. Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group. Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis. Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.