伴肾小动脉硬化病变的IgA肾病的临床病理特点及预后

该研究为回顾性研究, 分析2010年3月至2021年3月首都医科大学附属北京安贞医院866例IgA肾病(IgA nephropathy, IgAN)患者的临床资料, 探讨伴肾小动脉硬化病变的IgAN患者的临床病理及肾脏预后, 并初步探讨补体异常活化是否参与IgAN肾小动脉硬化病变的损伤。根据肾组织病理有无肾小动脉硬化病变分为肾小动脉硬化病变组和无肾小动脉硬化病变组, 比较两组间临床病理表现及预后。结果显示, 与无肾小动脉硬化病变组(n=236)相比, 肾小动脉硬化病变组(n=630)IgAN患者具有较高比例的高血压病史及恶性高血压病史, 较高水平的尿白蛋白肌酐比值、24 h尿蛋白量及血尿酸, 较低的估算肾小球滤过率, 较严重的牛津分型MEST-C病变(均P < 0.05)。Cox回归分析结果显示, 肾小动脉硬化病变是IgAN进展至主要终点事件(终末期肾病、估算肾小球滤过率下降≥30%或全因死亡)的独立影响因素(HR=6.437, 95%CI 2.013～20.585, P=0.002)。肾组织病理显示肾小动脉硬化病变组(n=98)IgAN患者的肾小动脉壁补体C3c沉积强度高于无肾...     

12例C3肾小球肾炎的临床病理特点及其血浆补体活化分析

目的 研究新命名的C3肾小球肾炎的临床和病理特点,明确血浆补体活化状况及其与临床的相关性。 方法 回顾性分析我科1999年1月至2010年6月符合最新C3肾小球肾炎定义的12例患者的临床病理资料,区分为膜增生型（MPGN）和非MPGN型。测定肾活检当天血浆部分补体成分水平以明确补体活化途径,分析补体活化产物与临床的相关性。 结果 12例患者中10例为非MPGN型,2例为MPGN型。所有患者均有蛋白尿。10例非MPGN型中2例为肾病水平蛋白尿,6例伴镜下血尿,1例伴肉眼血尿,2例伴肾功能减退。2例MPGN型中1例为肾病水平蛋白尿,伴镜下血尿、高血压、肾功能减退;另1例为单纯蛋白尿,伴高血压,而肾功能正常。所有患者血浆C3均在正常范围,但血浆B因子水平显著低于健康对照组（n=10）,Ba、C3a、C4a和C5a水平均显著高于健康对照组。血浆Ba水平与尿蛋白量呈正相关;而C3a、C4a、C5a与尿蛋白量、Scr无相关。非MPGN型C3肾小球肾炎多表现为轻度系膜增生,4例患者出现不同程度新月体。MPGN型则与I型MPGN类似,其中1例47.1%肾小球出现新月体。 结论 本组C3肾小球肾炎中以非MPGN型为主;临床上多表现为肾炎综合征;病理多表现为轻度系膜增生性肾小球肾炎。补体旁路活化在C3肾小球肾炎中可能发挥重要作用。     

IgA肾病患者肾组织2型补体受体的表达及参与补体C3沉积的可能机制

目的探讨IgA肾病(IgA nephropathy, IgAN)患者肾组织系膜细胞2型补体受体(complement receptor 2, CR2)的表达及其参与补体C3沉积的可能机制。方法选取广东省人民医院2021年8月至2022年5月肾活检确诊的IgAN患者, 按照系膜区补体C3沉积强度将患者分为补体C3沉积<2+组和补体C3沉积≥2+组, 收集基线资料、血浆和肾组织样本(以肾癌周围正常肾组织作为对照组), 采用酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)检测患者的血浆IgA和补体C3浓度, 比较不同补体C3沉积组IgAN患者的临床和病理指标、血浆IgA和C3浓度;采用免疫荧光法检测IgAN患者肾组织和肾癌周围正常肾组织中IgA、补体C3和CR2表达及共定位情况。体外培养系膜细胞, 随机分为对照组和实验组, 实验组使用IgA蛋白(2 g/L)刺激系膜细胞8 h, Western印迹法和实时荧光定量PCR法检测系膜细胞CR2的表达;通过基因本体(gene ontology, GO)和京都基因与基因组百科全书(Kyoto e...     

肾组织补体C3沉积与糖尿病肾病病理及临床表现的关系

目的：探讨肾组织补体C3的沉积与糖尿病肾病病理及临床表现之间的关系。方法：回顾性分析我科2003年1月~2013年1月收治的2型糖尿病患者145例,根据病理分型标准对患者进行病理分型,统计不同病理类型补体C3的沉积情况,并以其为依据,分为C3阳性组及C3阴性组,比较两组在病理及临床指标之间的差异,并比较不同病理类型之间补体C3沉积的差异。结果：145例患者中,肾组织C3阳性者共49例（33.8%）,根据C3沉积情况将患者分为C3阳性组及C3阴性组,两组患者在年龄、糖尿病病程、血压、24 h尿蛋白定量、血清补体C3等方面差异无统计学意义（P〉0.05）,在血浆白蛋白、血清肌酐、估算肾小球滤过率方面的差异有统计学意义（P〈0.05或〈0.01）;随着病理等级的升高,C3沉积率升高,差异有统计学意义（P〈0.05或〈0.01）。结论：肾组织补体C3的沉积可能加重了糖尿病肾病患者的病理及临床改变。     

甲状腺乳头状癌microRNAs表达谱与临床相关性研究

目的 寻找甲状腺乳头状癌(PTC)中特异性表达的microRNAs,以提高PTC的早期诊断水平和判断PTC的侵袭性.方法 选取51例甲状腺手术组织标本,利用miRNA芯片技术寻找甲状腺良恶性结节之间有表达差异的microRNAs,并通过qRT-PCR验证差异性表达的microRNAs,分析其与PTC临床病理特征的相关性. 结果 (1)qRT-PCR结果显示miR-30a-3p(U=60,P=0.003),miR-146b-5p(U=40,P=0.001)及miR-199b-5p(U=69,P=0.007)在良恶性结节中存在差异性表达.(2)miR-199b-5p在包膜外浸润及颈侧区淋巴结转移的PTC患者中明显升高(P =0.010),侵袭性越强其表达越明显. 结论 miR-199b-5p,miR-30a-3p及miR-146b-5p能鉴别甲状腺结节的良恶性,miR-199b-5p与PTC的侵袭性正相关.     

补体C5抑制剂对急性胰腺炎大鼠肾细胞因子的调控作用

目的 观察补体C5抑制剂对急性胰腺炎大鼠肾细胞因子的调控作用.方法 Wistar大鼠42只,随机分为3组:正常对照组(HC组,n=6);AP造模组(AP组,n=18);AP造模+C5抑制剂组(AP-C5I组,n=18).分别在6、12、18 h三个时间点处死AP组、AP-C5I组各6只.分别测定其血C5a水平;采用实时荧光定量逆转录.聚合酶链反应(RT-PCR)方法测定各组大鼠肾组织中C5、IL-1β、TNF-α和IL-10 mRNA表达情况.结果 AP组血清C5a水平显著升高(P＜0.01、vs HC);AP-C5I组其水平显著降低(P＜0.01 vs AP).HC组肾内C5 mRNA表达较弱;AP组该值较HC组有显著增高,差异有统计学意义(P＜0.01 vs HC);AP-C5I组肾组织C5 mRNA表达较AP组无显著改变(P＞0.05 vs AP).AP组.肾组织IL-β、TNF-αmRNA在6 h明显增多并持续增至18 h(P＜0.01 vs HC),AP-C5I组两值较同时相AP组明显降低(P＜0.01 vs AP);AP组和AP-C5I组肾组织IL-10 mRNA水平于建模后先升后降,AP-C5I组于6 h和12 h较AP组差异有统计学意义(P＜0.05 vs AP).结论 补体C5抑制剂能够阻断补体系统的激活,并部分恢复肾组织促抗炎细胞因子平衡.     

移植肾IgA肾病临床病理及预后分析

目的探讨移植肾IgA肾病(IgAN)复发或新发的诱因及移植肾生存的危险因素。方法选取2012年11月至2018年12月浙江大学医学院附属第一医院经肾活检确诊为移植肾IgAN的患者,按照血肌酐(Scr)增高水平、估算肾小球滤过率(eGFR)下降率分为稳定组(Scr升高值<20μmol/L,eGFR下降率<10%)和进展组(Scr增高但未达翻倍值,30%相似文献   

补体C5抑制剂对大鼠出血坏死性胰腺炎时肾损害的保护作用

本实验通过检测急性出血坏死性胰腺炎大鼠血清补体C5a蛋白水平和肾内C5 mRNA表达情况,结合血清尿素氮(BUN)、肌酐(Cr)浓度肾功能指标和肾脏病理形态学改变,评价补体C5抑制剂对胰腺炎肾损害的保护作用。     

补体-中性粒细胞反馈在过度训练致急性肾损伤中的作用研究

目的:探讨眼镜蛇毒因子(CVF)预处理是否通过消耗补体降低炎症反应,保护过度训练大鼠减轻肾损伤,以期为临床提供新的治疗靶点。方法:45只清洁级雄性Wistar大鼠随机分为正常对照组(NC),模型组(OT),过度训练+蛇毒因子干预组(CVF+OT)。分别于过度训练后0 h、6 h、24 h处死大鼠。采用全自动生化分析仪检测血清肌酐(Cr)、尿素氮(BUN)变化,ELISA法测定肾组织IL-1β含量;比色法检测髓过氧化物酶(MPO)活性;免疫组化及Western-blot法检测肾组织C5a的表达。结果:与NC组相比,OT组肾组织Cr、BUN明显高于对照组,在6 h水平最高(P <0. 05),24 h下降(P>0. 05);CVF+OT组两指标较同时间点OT组降低但仍高于NC组水平(P <0. 05),24 h均下降(P> 0. 05)。OT组肾组织IL-1β、MPO、C5a明显高于对照组,其中IL-1β在6 h水平最高,24 h稍降,MPO及C5a则进行性升高,CVF+OT组两指标较同期OT组降低但仍高于正常水平(P <0. 05)。结论:补体-中性粒细胞反馈的级联放大反应在过度训练致急性肾损伤的发生发展具有重要作用,抑制补体过度激活可以保护肾组织。     

糖尿病肾病患者的病理分型与免疫功能的相关性分析

目的探讨糖尿病肾病(DN)患者的病理分型与免疫功能的相关性。方法回顾性分析2015年2月到2019年2月在本院肾内科收治的78例DN患者的临床资料并作为DN组,同期选择肾脏功能正常者30例作为对照组。记录两组患者的肾功能指标与DN组患者的病理分型,免疫组化检测两组患者的C3aR.C5aR表达情况并进行统计分析。结果在DN组78例患者中,病理判断为I型40例,I型20例,皿型10例,V型8例。DN组的血肌酐、血尿素氮.C反应蛋白(CRP)含量显著高于对照组,差异有统计学意义(P<0.05)。DN组肾组织的C3aR.C5aR免疫组化阳性细胞百分比均显著高于对照组(P<0.05)。在DN组患者中,Pearson相关分析显示患者的病理分型与血肌酐(r=0.603,P=0.000)、血尿素氮(r=0.537,P=0.001).CRP含量(r=0.558,P=0.001)和C3aR(r=0.544,P=0.002)、C5aR(r=0.478,P=0.008)免疫组化阳性细胞的百分比呈显著正相关性。结论DN患者的病理分型与C3aR,C5aR免疫功能有显著相关性,其可影响DN的发生与发展。     

Role of C3a and C5a in focal segmental glomerulosclerosis

Objective To study the role of C3a and C5a in focal segmental glomerulosclerosis (FSGS) patients. Methods (1) A total of 66 patients with FSGS confirmed by renal biopsy were selected, including 18 cases of tip lesion, 11 cases of perihilar, 22 cases of not otherwise specified (NOS), 10 cases of cellular, and 5 cases of collapsing FSGS. The normal renal tissue resected from patients with kidney tumor was taken as a negative control. The expression of C3a and C5a in renal tissues was detected by immunohistochemistry. (2) Serum and urine samples from these 66 FSGS patients were collected, and serum and urine samples from 10 healthy adult selected from the same physical examination center in the same term were used as normal controls. The levels of C3a and C5a in serum and urine were detected by enzyme-linked immunosorbent assay (ELISA). Results (1) Immunohistochemical results showed that C3a and C5a were deposited in glomerulus of FSGS patients, and no deposition in normal renal tissues. The semi-quantitative score showed that kidney C3a score was significantly correlated with serum creatinine (r=0.547, P＜0.001) and 24 h urine protein (r=0.329, P=0.007) in FSGS patients, and kidney C5a score was also significantly correlated with serum creatinine (r=0.415, P＜0.001) and 24 h urine protein (r=0.414, P＜0.001) in FSGS patients. (2) The levels of serum C3a and C5a in FSGS patients were higher than those in healthy adults (both P＜0.05), but there was no significant difference among the five pathological types (P＞0.05). The levels of urinary C3a/urinary creatinine, urinary C5a/urinary creatinine were higher in FSGS patients than those in healthy adults (all P＜0.05). The levels of urine C3a/urinary creatinine and urinary C5a/urinary creatinine in collapsing FSGS were higher than other FSGS types (all P＜0.01), but there was no significant difference among the tip lesion, the perihilar, the not otherwise specified and the cellular (P＞0.05). (3) Urinary C3a/urinary creatinine levels were significantly correlated with serum creatinine (r=0.774, P＜0.001) and 24 h urine protein (r=0.430, P＜0.001) in FSGS patients, and urinary C5a/urinary creatinine levels were also significantly correlated with serum creatinine (r=0.677, P＜0.001) and 24 h urine protein (r=0.333, P=0.007) in FSGS patients. Conclusion Complement C3a and C5a may be involved in the pathogenesis of FSGS and may be related to the severity of FSGS.     

Elevated urinary excretion of the C5b-9 complex in membranous nephropathy.

In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar mechanism might be operative in human membranous nephropathy, we measured urinary excretion of C5b-9 and C5 in 146 proteinuric patients with biopsy-proven glomerular diseases or diabetes mellitus. Urinary excretion of C5b-9 relative to C5 excretion was higher in 40 patients with membranous nephropathy than in 106 patients with proteinuria due to non-membranous glomerulonephritis when analyzed by covariance analysis (P less than 0.0002). Urinary C5b-9 excretion was higher in membranous nephropathy than in membranoproliferative glomerulonephritis (N = 13, P less than 0.05), minimal change-focal sclerosis (N = 33, P less than 0.001), mesangial proliferative glomerulonephritis (N = 9, P less than 0.02) and IgA nephropathy (N = 7, P less than 0.025). Urinary C5b-9 excretion was also higher in patients with lupus nephritis (N = 18, P less than 0.02) compared to those with non-membranous glomerulonephritis. The lupus patients with the highest excretion had clinical or pathological features of membranous nephropathy. Nine patients with membranous nephropathy and elevated urinary C5b-9 excretion had a shorter duration of disease (P less than 0.05), lower serum creatinine levels (P less than 0.05) and more proteinuria (P less than 0.02) than the 31 membranous nephropathy patients with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal C3 synthesis in idiopathic membranous nephropathy: correlation to urinary C5b-9 excretion

Renal C3 synthesis in idiopathic membranous nephropathy: Correlation to urinary C5b-9 excretion. BACKGROUND: Complement activation plays a central pathogenetic role in idiopathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 gene expression has been described in several nephropathies. METHODS: The aim of this study was to investigate the renal C3 gene expression by in situ hybridization in IMN and to correlate it with histopathologic, pathophysiologic, and immunologic (urinary C5b-9) indices of disease activity. RESULTS: C3 was expressed in 77% of 22 renal biopsies of IMN patients, mainly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescence. The intensity of C3 gene expression by both glomerular and tubulointerstitial compartments correlated with the glomerular stage of disease (P = 0. 0023 and P = 0.0214, respectively). Although no correlation was found with proteinuria, serum creatinine at renal biopsy time was strongly associated with renal C3 expression. IMN patients showed a trend of increased urinary C5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0.0143). CONCLUSION: Renal C3 production, mainly at the tubular level, may be induced by urinary excretion of C5b-9 in IMN and may have a pathogenetic role in the tubulointerstitial damage that can be associated with this disease.     

Evaluation of urinary factor H excretion in patients with idiopathic membranous nephropathy

BACKGROUND: The complement system plays an important role in renal pathogenesis, and C5b-9, a terminal complement complex, is regarded as the principal mediator of proteinuria in idiopathic membranous nephropathy(MN). Since factor H regulates complement activation at the C3 step and is a crucial factor in complement-mediated tissue injury, the urinary excretion of factor H in patients with idiopathic MN was investigated. METHODS: Seven patients with biopsy-proven idiopathic MN were studied for twenty-four weeks. Urinary factor H levels were measured by ELISA from regularly collected urine samples, and then evaluated and compared with assays of urinary protein and C5b-9 excretion. RESULTS: During the study, five patients were treated with steroid therapy. All seven patients maintained stable renal function and showed a decline in urinary protein excretion. The mean level of urinary factor H was markedly elevated (156.1 +/- 47.1 U/mg U-Cr) before treatment (0 week), and gradually declined to 127.2 +/- 43.5 U/mg U-Cr at 12 weeks, and to 64.7 +/- 26.9 U/mg U-Cr) at 24 weeks. This followed decreases in urinary protein and urinary C5b-9 excretion. Percent change in urinary factor H level significantly decreased 24 weeks after treatment without affecting the plasma factor H level. CONCLUSION: These results suggest that factor H contributes to the regulatory mechanism of in situ complement activation, and thus the study of urinary factor H levels, as well as urinary C5b-9, may be significant in idiopathic MN.     

Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy.

We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.     

Evaluation of urinary decay accelerating factor and CD59 in renal damage

Background Decay accelerating factor (DAF) and CD59 (protectin) are complement regulatory proteins that can be detected in soluble form in urine. We studied the relationship between renal disease and the mechanisms involved in the urinary excretion of complement regulatory proteins. Methods Urine samples were obtained from 143 patients with renal disease and 61 individuals with normal renal function, who served as control subjects. As a model of limited tubular injury, we also studied the urine of 5 patients who were being treated with cisplatin for lung cancer; samples were collected before administration of the chemotherapeutic agents (day 0) and every morning during the observation period (15 days). Urinary DAF, CD59, and SC5b-9 (a complement component) were measured by enzyme-linked immunosorbent assay, using monoclonal antibodies. Results In the patients with renal disease, urinary DAF and CD59 levels were higher than in healthy control subjects (P<0.001). The correlations between urinary DAF and CD59 levels were significant in patients with renal disease and healthy individuals (P<0.001). Urinary SC5b-9 was not correlated with either urinary DAF or CD59 in patients with IgA nephropathy. In the patients with lung cancer, urinary DAF and CD59 were elevated after the administration of cisplatin. This was accompanied by an increase in the secretion of urinaryN-acetyl-β-d-glucosaminidase and β₂-microglobulin, both of which are markers for tubular injury. Conclusion These results suggest that elevated levels of urinary DAF and CD59 are related to renal disease, as well as to the limited tubular injury associated with cisplatin treatment.     

Correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis

Objective To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN). Methods Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve. Results A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older (t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006)，higher urine protein quantitation (Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 (Z=3.469, P＜0.001; t=1.744, P＜0.001), higher systemic lupus erythematosus disease activity index (t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher (Z=-1.866, P=0.002; t=-5.005, P＜0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P＜0.001; χ2=15.695, P＜0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients (OR=0.966, 95％CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine /end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.     

Terminal complement complexes in acute poststreptococcal glomerulonephritis

Activation of the complement cascade occurs in most cases of acute poststreptococcal glomerulonephritis (APSGN) and results in the formation of the terminal complement complexes (TCC). To examine the possible role of TCC in the pathogenesis of glomerular injury in APSGN, we studied 30 patients with the clinical diagnosis of APSGN. All patients had an elevated plasma SC5b-9 concentration at the onset of clinical nephritis. Serial plasma concentrations showed an inverse linear relationship with time after onset of clinical disease (r=–0.59,P=0.0008), while plasma C3 concentrations showed a positive linear relationship (r=0.78,P=0.0001). Renal biopsies of 5 patients demonstrated co-localization of C5b-9, S-protein, and C3 deposition in a glomerular capillary loop and mesangial distribution. Urinary excretion of TCC in the acute phase of APSGN was not elevated and was not a useful marker of disease activity. These data suggest that in APSGN with terminal complement pathway activation the local generation of TCC may contribute to the pathogenesis of the disease.     

Urinary porphyrin excretion in normal children and adults

The relationship of random urinary porphyrin and creatinine values as functions of age and sex was examined in a normal population. Total urinary porphyrin was measured by a solvent extraction technique, while urinary creatinine was evaluated by an alkaline picrate method. Random urine specimens from 120 healthy patients (81 children and 39 adults) were evaluated. In both pediatric and adult populations, a strong correlation was found between urinary concentrations of porphyrin and creatinine (r = 0.7, P less than 0.0001). Urinary porphyrin excretion in mumol/mol creatinine (micrograms/g) was inversely related to both age (r = -0.59, P less than 0.0001) and weight (r = -0.61, P less than 0.0001) until approximately 9 years of age or 30 kg. Urinary porphyrin excretion in children 9 to 18 years of age was lower than that of younger children (P less than 0.0001) and approached adult values. Sex was not found to be a factor until 9 to 18 years of age, when females had higher urinary creatinine concentrations (P less than 0.05), but lower urinary porphyrin excretions (P less than 0.05) than similarly aged males. The converse was observed when similar values of adult women were compared with those of adult men. Men also had higher urinary porphyrin concentrations than women (P less than 0.01). Men had increased urinary creatinine concentration (P less than 0.05) and decreased porphyrin excretion ratios (P less than 0.05) when compared with males 9 to 18 years of age. Women had significantly lower urinary creatinine (P less than 0.001) and porphyrin (P less than 0.001) concentrations than females 9 to 18 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Change and clinical significance of microRNA-148b-3p level in the serum of patients with type 2 diabetes mellitus and diabetic nephropathy

Objective To detect the serum microRNA-148b-3p level in patients with diabetes mellitus and diabetic nephropathy, and to analyze its correlation with clinical and pathological indexes. Methods The research crowd was divided into three groups (1) diabetic nephropathy group: biopsy with diabetic nephropathy (n=25, 14 males, 11 females); (2) type 2 diabetes mellitus group: type 2 diabetes mellitus patients with normal urinary microalbumin /urinary creatinine value (n=10, 4 males, 6 females); (3) normal control group: healthy subjects (n=9, 3 males and 6 females). Clinical indicators included gender, age, 24-hour urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), urea (Urea), cystatin-C (Cys-C), blood albumin (ALB), urine microalbumin (UMA), triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum uric acid (UA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urine microalbuminuria / urinary creatinine (UACR), and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula. Real-time quantitative PCR was applied to verify the expression of microRNA-148b-3p in serum samples of the research crowds. The relationships between microRNA-148b-3p level and clinical features was also analyzed. Results The levels of serum microRNA-148b-3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group (P＜0.05, respectively). The level of serum microRNA-148b-3p was significantly correlated with HDL-C (r=-0.374, P=0.013), UMA (r=0.426, P=0.004), FBG (r=0.330, P=0.046) and TG (r=0.423, P=0.005). Multiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level (β=0.338, P=0.044). The area under the receiver operating characteristic curve (ROC) of serum microRNA-148b-3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665, respectively. Conclusions The level of serum microRNA-148b-3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases. The level of UMA is independently associated with serum microRNA-148b-3p level. Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic nephropathy.