Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.     

基于真实世界数据探讨中医药治疗糖尿病肾病用药规律的研究＊

目的 基于临床信息系统分析总结真实世界的数据，采用数据挖掘的方法探讨中医药治疗糖尿病肾病的用药规律。方法 收集2018年1月-2020年12月上海中医药大学附属曙光医院宝山分院健康信息系统确诊的糖尿病肾病的门诊或住院患者的诊疗信息，建立Excel数据库，采用Excel 2010软件统计高频药物的四气、五味、归经及功效；使用SPSS Modeler 18.0软件中的Apriori算法分析关联规则，采用web节点建构药对关联网状图；运用SPSS 25统计软件进行因子分析。结果 本研究最终纳入477例接受中药饮片治疗的DKD患者，在1203条方剂信息中，涉及中药462种；使用频数排名前5位的中药分别是黄芪、黄精、石斛、山茱萸、麦冬；使用频数前5类的中药类别分别是补气药、补阴药、清热燥湿药、活血调经药、息风止痉药；在30味高频药物中，苦、甘、辛药味最为常见；药性寒、温数量接近；归脾经、肝经、肺经、肾经居多；关联规则提示，药物组合中置信度最高的组合为地龙-当归-僵蚕，因子分析共得到5个有效因子，累积贡献率为47.33%。结论 中医药治疗DKD在补益气血阴阳的同时，兼顾对瘀血、湿邪和痰饮的治疗，结合证型，可考虑使用黄芪、黄精、石斛、山茱萸、麦冬、金蝉花等药物的使用，清热燥湿药物如黄连、黄芩、黄柏可适当加入，为使邪有去处，大黄、车前子或可增添疗效。     

2型糖尿病患者扫描式葡萄糖监测系统指标与尿白蛋白/肌酐比值的相关性研究

背景 随着血糖监测技术的发展，近些年来人们开始使用扫描式葡萄糖监测系统（FGMS）"全景式"地观察2型糖尿病（T2DM）患者的血糖水平，明确FGMS指标与T2DM并发症之间的关系有助于提高其临床应用价值，但目前相关研究较少。 目的 探究佩戴FGMS的T2DM患者葡萄糖在目标范围内时间（TIR）等指标与尿白蛋白/肌酐比值（UACR）的相关性。 方法 选取2019年1月至2021年10月于北京大学人民医院老年科就诊并佩戴FGMS的T2DM患者79例，以尿液检查中UACR是否<30 mg/g将患者分为无白蛋白尿组（n=50）和白蛋白尿组（n=29）。比较两组患者的临床特征、实验室检查指标及FGMS指标等。采用Pearson相关、Spearman秩相关分析探讨TIR、高血糖时间（TAR）与糖化血红蛋白（HbA1c）的相关性。分别采用Pearson相关、Spearman秩相关、偏相关分析探讨FGMS指标与lnUACR的相关性。使用多因素Logistic回归分析探究T2DM患者发生白蛋白尿的影响因素，采用受试者工作特征（ROC）曲线评估TIR对白蛋白尿的预测价值。 结果 白蛋白尿组T2DM病程长于无白蛋白尿组，三酰甘油（TG）、HbA1c、平均血糖（MBG）、TAR、平均血糖标准差（SDBG）、最大葡萄糖波动幅度（LAGE）、平均葡萄糖波动幅度（MAGE）、连续每隔2 h血糖净作用（CONGA2）高于无白蛋白尿组，TIR低于无白蛋白尿组（P<0.05）。Pearson相关、Spearman秩相关分析结果显示，TIR与HbA1c呈负相关（P<0.001），TAR与HbA1c呈正相关（P<0.001）。Pearson相关、Spearman秩相关、偏相关分析结果均表明，TIR与lnUACR呈负相关（P<0.001），MBG、TAR、SDBG、LAGE、MAGE、CONGA2与lnUACR呈正相关（P<0.001）。多因素Logistic回归分析结果显示，TIR>70%〔OR=0.038，95%CI（0.003，0.467）〕是T2DM患者出现白蛋白尿的保护因素（P<0.05），TAR升高〔OR=1.046，95%CI（1.000，1.094）〕是T2DM患者出现白蛋白尿的危险因素（P<0.05）。TIR预测T2DM患者出现白蛋白尿的ROC曲线下面积（AUC）为0.784〔95%CI（0.674，0.894）〕（P=0.003），灵敏度为78%，特异度为83%，最佳切点为69.71%。 结论 在FGMS指标中，TIR>70%是T2DM患者出现白蛋白尿的保护因素，TAR升高是T2DM患者出现白蛋白尿的危险因素。同时，SDBG、LAGE、MAGE、CONGA2等多种反映血糖波动的指标也与UACR密切相关。对TIR水平较低及TAR、SDBG、LAGE、MAGE、CONGA2水平较高的T2DM患者进行FGMS筛查有助于早期识别及预防白蛋白尿的发生、发展。     

尿酸性肾病中医分型与氧化应激指标的相关性研究

目的：探讨尿酸性肾病中医分型与氧化应激相关性。方法：采用回顾性分析方法对2017年12月至2019年9月北京中医药大学第三附属医院收治的尿酸性肾病患者105例进行研究，选择同时期正常健康者105例作为对照，参考《中药新药临床研究指导原则》将105例尿酸性肾病和临床常见证型相结合，分成脾肾气虚18例、气阴两虚证19例、肝肾阴虚16例、阴阳两虚12例、湿热蕴结19例、瘀血阻滞17例、痰浊内阻13例，均在入院次日清晨空腹抽取静脉血，检测氧化应激氧化应激、肾功能损害指标，比较不同组别在氧化应激指标含量水平变化情况，比较中医分型和氧化应激、肾功能损害指标水平变化。结果：1）尿酸性肾病组总抗氧化能力（T-ACO）、晚期蛋白氧化物（AOPP）、血清丙二醇（MDA）、超氧化物歧化酶（SOD）含量水平分别为（19.45±3.42）U/mL、（42.45±3.53）μmol/L、（4.52±1.23）nmol/L、（76.78±5.64）U/mL，正常对照组则分别为（10.76±1.31）U/mL、（20.84±1.28）μmol/L、（2.13±0.76）nmol/L、（130.85±16.75）U/mL，尿酸性肾病组T-ACO、AOPP、MDA较正常对照组显著偏高，SOD显著偏低（P<0.05）。2）虚证中阴阳两虚证SOD含量上较其他证型均偏低，而MDA、T-AOC、AOPP、胱抑素C（CysC）、β2微球蛋白、尿微量白蛋白（UMALB）、蛋白尿发生率则较其他证型均偏高，差异均有统计学意义（P<0.05），实证中瘀血阻滞证SOD含量较其他证型均偏低，而MDA、T-AOC、AOPP则较其他证型均偏高，差异均有统计学意义（P<0.05）。结论：尿酸性肾病中医分型的阴阳两虚证、瘀血阻滞证氧化应激水平、肾损害指标均显著升高，可结合该实验室检查进行临床干预。     

冬虫夏草预防糖尿病大鼠对比剂肾病机制研究

目的探讨冬虫夏草预防糖尿病大鼠对比剂肾病的机制。方法SD大鼠80只,腹腔注射链脲佐菌素(60 mg/kg)建立糖尿病模型,并随机分为对照组(C组)、对比剂肾病组(CIN组)、冬虫夏草低剂量组(L组)、冬虫夏草标准剂量组(M组)和冬虫夏草强化剂量组(H组)。L组、M组、H组大鼠分别给予冬虫夏草(2.0、2.5、3.0 g/kg)灌胃,C组、CIN组则以等量生理盐水灌饲,连续7天。7天后检测SCr、BUN、尿蛋白排泄率(UAE)、一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、总抗氧化能力(T-AOC)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子1(KIM-1)及IL-18。取左肾测病理和氧化应激指标;右肾用于Western Blot检测抗凋亡蛋白和促凋亡蛋白(包括:Bcl-2、Bax、Caspase-3、Caspase-9、p-Akt、p-mTOR、p-ERK、p-JNK、p-P70S6K)表达。结果与C组比较,CIN组SCr、BUN、UAE、MDA、NAGL、KIM-1、IL-18均明显升高,NO、T-SOD降低(P<0.05)。与CIN组比较,L组、M组、H组SCr、BUN、UAE、MDA均明显降低,NO、T-SOD升高(P<0.05);L组、H组NAGL、IL-18、降低(P<0.01),其中H组KIM-1均明显降低(P<0.01)。与L组、M组比较,H组SCr、BUN、UAE、MDA、NGAL、KIM-1、IL-18明显降低,NO、T-SOD升高(P<0.05)。与C组比较,CIN组Bcl-2、P-Akt、P-mTOR、P-P70S6K、P-ERK蛋白表达增加,Bax、P-JNK、Caspase-3、Caspase-9蛋白表达减少(P<0.05)。与CIN组比较,Bcl-2、P-Akt、P-mTOR、P-P70S6K、P-ERK蛋白表达在L组、M组、H组逐渐增加,其中H组最高(P<0.05),Bax、P-JNK、Caspase-3、Caspase-9蛋白表达L组、M组、H组逐渐减少,H组表达量最少(P<0.05)。结论冬虫夏草通过抗氧化应激、抑制脂质过氧化反应、抗凋亡等途径对糖尿病大鼠对比剂肾病发挥较好的保护作用,冬虫夏草强化剂量组优于低剂量组和标准剂量组。     

脂蛋白肾病1例报道及文献复习

近期重庆市中医院肾病科收治脂蛋白肾病(Lipoprotein glomerulopathy,LPG)1例。现回顾分析病例资料、中西医诊疗及随访情况,并进行文献复习、中医传统理论阐述及讨论。以提高临床对中医药诊治该病的认识。     

Hepcidin – Potential biomarker of contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions

PurposeContrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients.MethodsSerum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI.ResultsWe found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI.ConclusionsOur findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD.     

Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.