Comparison of the Antialbuminuric Effects of L-/N-type and L-type Calcium Channel Blockers in Hypertensive Patients with Diabetes and Microalbuminuria: The Study of Assessment for Kidney Function by Urinary Microalbumin in Randomized (SAKURA) Trial

Objective: To clarify whether the L-/N-type calcium channel blocker (CCB) cilnidipine is more renoprotective than the L-type CCB amlodipine in patients with early-stage diabetic nephropathy.Methods: In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of cilnidipine and amlodipine were examined in renin-angiotensin system (RAS) inhibitor-treated patients with hypertension (blood pressure [BP]: 130-180/80-110 mmHg), type 2 diabetes, and microalbuminuria (urinary albumin to creatinine [Cr] ratio [UACR]: 30-300 mg/g).Results: Patients received cilnidipine (n = 179, final dose: 10.27 ± 4.13 mg/day) or amlodipine (n = 186, 4.87 ± 2.08 mg/day) for 12 months. Cilnidipine and amlodipine equally decreased BP. The UACR values for the cilnidipine and amlodipine groups were 111.50 ± 138.97 and 88.29 ± 63.45 mg/g, respectively, before treatment and 107.93 ± 130.23 and 89.07 ± 97.55 mg/g, respectively, after treatment. The groups showed similar changes for the natural logarithm of the UACR, serum Cr, and estimated glomerular filtration rate.Conclusions: Cilnidipine did not offer greater renoprotection than amlodipine in RAS inhibitor-treated hypertensive patients with type 2 diabetes and microalbuminuria.     

Poor metabolic control and predisposition to hypertension,rather than hypertension itself,are risk factors for nephropathy in type 2 diabetes

Sodium-lithium countertransport (Na⁺/ Li⁺ CT) activity in erythrocytes has been shown to be high in a subset of patients with essential but not secondary hypertension and in type 1 (insulin-dependent) diabetic patients with nephropathy. More recently it has been shown that the presence of a major gene for Na⁺/Li⁺ CT, or another closely linked gene, rather than the actual level of Na⁺/Li⁺ CT, increases the risk of hypertension onset. The aim of the present study was to investigate whether Na⁺/Li⁺ CT activity is associated with hypertension and nephropathy in type 2 (non-insulin-dependent) diabetes. We studied 18 type 2 diabetic patients with normal blood pressure levels (systolic 140 and diastolic 85 mmHg) and albumin excretion rate (15 g/min), 19 type 2 diabetic patients with hypertension (systolic 145 and diastolic 90 mmHg) and a normal albumin excretion rate (15 g/min) and 19 type 2 diabetic patients with an increased albumin excretion rate (20 g/min), irrespective of blood pressure levels. Eighteen normal subjects, matched for sex and age, served as controls. Na⁺/Li⁺ CT activity in erythrocytes was higher in type 2 diabetics with a high albumin excretion rate (486±148 mol/l erythrocytes per hour,P<0.01) and in hypertensive diabetics (410±129,P<0.05), but not in normotensive diabetics (340±141), than in controls (282±96) (mean±SD). Body mass index was higher in diabetics with hypertension and in those with an abnormal albumin excretion rate than in normotensive diabetics and controls. Blood pressure levels were higher in diabetic patients with an increased albumin excretion rate than in normotensive diabetics and controls. Of diabetic patients with a high albumin excretion rate 26% had normal diastolic blood pressure levels. Diabetics with a high albumin excretion rate had higher glycated haemoglobin, cholesterol and triglyceride levels and a longer duration of diabetes than hypertensive diabetics with a normal albumin excretion rate. The association of these clinical features in type 2 diabetes closely resembles that previously reported in type 1 diabetes. A novel finding of the present study is that predisposition to hypertension, as indicated by high Na⁺/Li⁺ CT, seems to confer a susceptibility to the development of renal damage in type 2 diabetes, partially independent of blood pressure levels per se, and that diabetic patients with high Na⁺/Li⁺ CT and hypertension are, to some extent, protected against the development of nephropathy when the metabolic control is tighter and the duration of the disease shorter.     

糖尿病肾病患者血清肝细胞生长因子含量变化及其临床意义

目的：探讨血清肝细胞生长因子（HGF）在糖尿病肾病患者体内含量变化及关系。方法：将38例2型DM患者分为单纯DM组和伴血管病变的DM组各19例,同时用24名体检健康者作为对照,检测其血清HGF、NO及血浆内皮素（ET）水平。结果：与对照组比较,单纯DM组和伴血管病变的DM组血清HGF、血浆内皮素（ET）含量显著升高,血清NO水平显著下降（P〈0.05）。与单纯DM组比较,伴血管病变的DM组血清HGF、NO和血浆ET改变显著,差异有统计学意义（P〈0.05）。相关分析显示,血清HGF水平与患者的ET水平呈正相关,与NO水平呈负相关（spearman相关系数分别为0.418和-0.561,P均〈0.01）。结论：血清HGF水平反映了2型DM患者的血管内皮受损程度,可用于临床上监测DM患者的血管病变情况。     

血清纤维结合蛋白测定在肾病中的临床应用

目的探讨血清纤维结合蛋白（fibronection,Fn）水平的变化在诊断肾脏疾病中的作用和临床意义。方法收集102例确诊肾病患者及50例健康对照者血清标本,采用透射比浊法测定血清Fn的水平。结果各组间Fn检测水平差异有统计学意义（P〈0．05）,各肾病组Fn检测水平均低于对照组,且差异均有统计学意义（P均〈0．01）。急性肾小球肾炎、慢性。肾小球肾炎、肾病综合征组Fn水平均高于肾衰组,且差异均有统计学意义（P均〈0．01）。与传统肾功能生化指标相比,Fn的临床灵敏度较低,仅为48．0％。Fn与常用肾功能生化指标均有一定相关性（P均〈0．01）。结论Fn足评估肾病进展的一个良好指标,能够对观察患者病情及指导临床治疗提供帮助。     

2型糖尿病肾病患者血清同型半胱氨酸、叶酸及维生素B12水平的相互关系

目的探讨2型糖尿病肾病患者空腹血浆同型半胱氨酸（Hcy）、叶酸（FA）及维生素B12（VitB12）水平的相互关系及其影响因素。方法165例2型糖尿病患者根据尿微量白蛋白排泄率（UAER）分为尿微量白蛋白正常糖尿病组（A组）、早期。肾病组（B组）、临床肾病组（C组）,用酶联免疫吸附试验分别检测各组患者血浆Hey浓度,并同步应用发光免疫法测定血清FA、VitB12水平,与48例正常对照者（D组）进行比较。结果A组：UAERl（1．6±5．2）μg／min、HCY（14．8±3．6）μmol／L、FA（9．02±2．06）nmol／L、VitB12（552±162）pmol／L;B组UAER（82．9±45．8）μg／min、HCY（21．1±2．3）μmol／L、FA（7．85±2．45）nmol／L、VitB12（436±135）pmol／L;C组UAER（348．1±123．2）μg／min、HCY（32．3±2．5）μmol／L、FA（5．78±2．33）nmol／L、VitB12（292±92）pmol／L;D组UAER（10．9±5．3）μg／min、HCY（9．1±2．2）μmol／L、FA（10．39±2．93）nmol／L、VitB12（688±208）pmol／L。各组血Hey水平均明显高于正常对照组（P〈0．05）,C组又高于A组和B组（P〈0．05）,而FA、VitB12水平与对照组相比均显著降低（P〈0．05）,C组又低于A组和B组（P〈0．05）。Hey与UAER呈正相关（P〈0．01）,,与FA、VitB12呈负相关（P〈0。01）。结论定期测定糖尿病患者血浆Hcy、FA和VitB12有助于预测、判断2型糖尿病肾病的发展。     

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B–cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.     

Urinary epidermal growth factor in kidney disease: A systematic review

Urinary epidermal growth factor (uEGF) is primarily produced by the kidney, and alterations of it have been associated with several kidney diseases. The aim of this review was to describe uEGF levels in presence or progression of kidney diseases. We conducted a systematic review of observational studies with uEGF determination, patients with acute kidney injury, chronic kidney disease, primary or secondary nephropathy, or renal cancer were included. Studies were searched in Medline, Google Scholar, Science Direct, and EBSCO up to August 2, 2021. Participants and measurements characteristics from which uEGF were determined as the specificity, sensitivity, and the area under the ROC curve, whenever available, were gathered. 53 studies were included, the most frequent kidney diseases studied were acute kidney injury, chronic kidney disease, and diabetic nephropathy. In most studies, uEGF levels were lower in cases than in controls. Studies showed that uEGF levels can predict presence or progression of acute kidney injury, chronic kidney disease, and nephropathy. Heterogeneity in the reported uEGF values can be attributed to the different techniques, sampling, and ways of reporting uEGF values.Although uEGF values are lower in patients with almost all kidney diseases and their progression, uEGF evaluation methods should be standardised to be used as a biomarker in clinical practice.     

早期糖尿病肾病血清 NGAL与致动脉硬化指数的关系

目的观察在早期糖尿病肾病(DN)患者血清中性粒细胞明胶酶相关载脂蛋白(NGAL)水平的变化,探讨NGAL与致动脉硬化指数(AIP)的关系。方法选取尿微量白蛋白/肌酐300 mg/g的糖尿病患者120例为糖尿病组,根据尿微量白蛋白/肌酐分为正常白蛋白尿组和早期DN组,另选取健康体检者60例作为对照组。检测各组血清甘油三酯(TG)、胆固醇(CHOL)、高密度脂蛋白(HDL)、NGAL、超敏C反应蛋白(hs-CRP)等,并计算致动脉硬化指数;分析3组NGAL、hs-CRP、AIP的变化。按照AIP三分位数将所有研究对象分成低、中、高水平3组,分析其NGAL和hs-CRP的变化。对所有变量进行简单线性相关和多元线性逐步回归分析。结果与对照组比较,正常白蛋白尿组和早期DN组NGAL、hs-CRP、AIP水平明显升高(P0.001);与正常白蛋白尿组比较,早期DN组NGAL、hs-CRP、AIP水平明显升高(P0.001)。血清NGAL水平随AIP上升而明显上升(P0.001)。AIP与hsCRP、NGAL呈正相关(r=0.296,0.313,P0.05);NGAL、hs-CRP为AIP的独立影响因素。结论血清NGAL是监测糖尿病早期肾损伤的指标。NGAL是一个急性时相反应蛋白,参与了糖尿病肾病动脉粥样硬化的发生发展。     

基于中医传承辅助系统肾病蛋白尿防治组方配伍规律的数据挖掘研究

目的 中医传承辅助系统分析白志军教授治疗肾病蛋白尿的组方用药规律，为肾病蛋白尿的临床遣方用药及新药开发提供依据。方法 搜集2018年1月-2020年12月白志军教授治疗肾病蛋白尿的中药处方（包括门诊处方和住院处方），运用中医传承辅助系统（V1.1）和Mircrosoft Office Excel对筛选出的中药方剂进行组方配伍规律分析。结果 共筛选出符合标准的中药处方110首，涉及中药139味，其中使用频次较高的中药为黄芪、白花蛇舌草、半枝莲、白茅根、党参、炙甘草、茯苓等；药味以甘味、苦味为主，药性以寒性、平性居多，归经多属胃、肺、脾、肝经；高频次药物组合有黄芪＋白花蛇舌草、半枝莲＋白花蛇舌草、半枝莲+黄芪、半枝莲+黄芪＋白花蛇舌草、白茅根+黄芪等；通过熵层次聚类分析得到5个新方。结论 肾病蛋白尿的病机特点多为本虚标实，本虚主要是脾肾亏虚、气阴不足，标实为瘀血、热毒、水湿。主要治则是以健脾固肾益气为首要，重视清热解毒，贯穿活血化瘀。