Correlation between podocyte excretion and proteinuria in diabetic nephropathy patients

Objective:To observe the podocyte injury in diabetic nephropathy(DN) patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria,blood glucose,serum creatinine in different phases in DN patients.Methods:Urinary podocytes and the podocalyxin(PCX) expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method.The DN patients were divided into three groups according to the volume of proteinuria,namely small,medium and large volume proteinuria groups.The podocytes in the urine of every group were calculated.The DN patients were divided into five groups according to the chronic kidney disease(CKD) phases,then the positive podocytes in urine were calculated.Meanwhile,the 24-hour protein in urine,fasting blood glucose(FBG) and the serum creatinine of DN patients were tested.The correlations among the proteinuria,serum creatinine,FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed.Results:Urinary positive podocytes were found in 88% of the patients with DN,whereas podocytes were found in 0% of patients with minimal changed disease(MCD) and healthy cases.The expression of PCX was absent in DN patients.In contrast,PCX was expressed integrally in MCD patients.The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group,2.15±0.70/ml in the medium-volume proteinuria group,and 3.48±1.27/ml in the large-volume proteinuria group.There was no significant difference between the small-and medium-volume proteinuria groups,and there were significant differences between other groups(P<0.05).The positive podocyte number tended to increase as proteinuria was increased.By Pearson analysis,the correlation between podocyte number and proteinuria was positive statistically.The difference of the number of positive podocytes in urine from different groups of DN patients,CKD Ⅰ-Ⅴ group was significant statistically.The correlation between serum creatinine of CKD Ⅰ-Ⅲ group and positive podocytes in urine was positive statistically.The correlation between serum creatinine of CKD Ⅳ-Ⅴ group and positive podocytes in urine was not significant statistically.The correlation between FBG and positive podocytes in urine was not significant either.Conclusion:The mechanism of the podocyte injury in DN patients is present.The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ-Ⅲ DN patients,but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.

Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups;Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN;therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

Non-Diabetic Nephropathies among Diabetic Patients of the Nephrology Department of Dakar

Introduction: Diabetic nephropathy is the most common cause of kidney disease in diabetics. However, in some cases the clinical symptoms is not typical and nephropathy may be different from diabetic and require the use of renal biopsy (RB) which is not usually indicated unless non-diabetic nephropathy (NND) is suspected. The objective of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) among the diabetic patients and to analyse the different predictive factors of its occurrence. Patients and methods: It was a retrospective, descriptive and analytical study which is carried out at the nephrology department of Aristide Le DANTEC hospital of Dakar over a period of 60 months. Diabetics with suspected NDN diagnosis based on renal anomalie that is associated with a recent diabetes, Acute renal failure with rapid progress, Diabetic retinopathy’s absence, and Extrarenal signs (cutaneous, digestive and articular) associated with an acute renal failure. Microscopic haematuria was included. The epidemiological, clinical, biological and histological parameters were collected and analysed using the SPSS, 3.5 version software. Results: Out of 34 biopsied diabetic patients, 12 had NDN that is a prevalence of 35, 3%. The average age was 49.88 ± 4.15 years, 0.78 for the sex-ratio and the mean duration of diabetes is 12.53 ± 4.7 years. Glomerular syndrome was found in 30 patients (88.23%), vascular nephropathy syndrome in 3 patients (8.82%) and tubule-interstitial nephropathy syndrome in only one patient (2.94%). Diabetic retinopathy (DR) and microscopic haematuria (HU) respectively existed in 10 patients (34%) and 15 patients (44. 12%). The Kidney biopsy (KB) indications were renal abnormalities associated with recent diabetes, acute renal failure with rapid progress, absence of DR, extrarenal signs associated with acute renal failure and microscopic haematuria. Twenty-two patients (64.7%) had diabetic nephropathy (DN) and 12 patients (38.2%) presented a NDN. Predictive factors of NDN diagnosis were a shorter diabetes duration (P = 0.0008), high blood pressure (P = 0.0015) and absence of DR (P = 0.005). Conclusion: Our data show that kidney injury in a diabetic is not always diabetic nephropathy. The Kidney biopsy (KB) is often needed in order to adopt an effective management.

Biomarkers in diabetic nephropathy: Present and future

Diabetic nephropathy(DN) is the leading cause of end stage renal disease in the Western world. Microalbuminuria(MA) is the earliest and most commonly used clinical index of DN and is independently associated with cardiovascular risk in diabetic patients. Although MA remains an essential tool for risk stratification and monitoring disease progression in DN, a number of factors have called into question its predictive power. Originally thought to be predictive of future overt DN in 80% of patients, we now know that only around 30% of microalbuminuric patients progress to overt nephropathy after 10 years of follow up. In addition, advanced structural alterations in the glomerular basement membrane may already have occurred by the time MA is clinically detectable.Evidence in recent years suggests that a significant proportion of patients with MA can revert to normoalbuminuria and the concept of nonalbuminuric DN is well-documented, reflecting the fact that patients with diabetes can demonstrate a reduction in glomerular filtration rate without progressing from normo-to MA. There is an unmet clinical need to identify biomarkers with potential for earlier diagnosis and risk stratification in DN and recent developments inthis field will be the focus of this review article.

Evolving spectrum of diabetic nephropathy

Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.

Diabetic nephropathy:Is it time yet for routine kidney biopsy?

Diabetic nephropathy(DN)is one of the most important long-term complications of diabetes.Patients with diabetes and chronic kidney disease have an increased risk of all-cause mortality,cardiovascular mortality,and kidney failure.The clinical diagnosis of DN depends on the detection of microalbuminuria.This usually occurs after the first five years from the onset of diabetes,and predictors of DN development and progression are being studied but are not yet implemented into clinical practice.Diagnostic tests are useful tools to recognize onset,progression and response to therapeutic interventions.Microalbuminuria is an indicator of DN,and it is considered the only noninvasive marker of early onset.However,up to now there is no diagnostic tool that can predict which patients will develop DN before any damage is present.Pathological renal injury is hard to predict only with clinical and laboratory findings.An accurate estimate of damage in DN can only be achieved by the histological analysis of tissue samples.At the present time,renal biopsy is indicated on patients with diabetes under the suspicion of the presence of nephropathies other than DN.Results from renal biopsies in patients with diabetes had made possible the classification of renal biopsies in three major groups associated with different prognostic features:diabetic nephropathy,non-diabetic renal disease(NDRD),and a superimposed non-diabetic condition on underlying diabetic nephropathy.In patients with type 2 diabetes with a higher degree of suspicion for NDRD,it is granted the need of a renal biopsy.It is important to identify and differentiate these pathologies at an early stage in order to prevent progression and potential complications.Therefore,a more extensive use of biopsy is advisable.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Study of 82 Patients and Review of the Literatures

Background: Worldwide, diabetic nephropathy-DN is the leading cause of end-stage kidney disease-ESKD, DN is a common cause of renal failure with a reported frequency of 10% - 15% in type-2-diabetes-mellitus-T2DM patients, however there is a great discrepancy between countries. The aim of the pre-sent study is to evaluate the findings of kidney biopsies performed on diabetic patients. Materials and Methods: We studied native kidney histopathological findings in the period from January 2016 till end of December 2018 done for patients with T2DM with chronic kidney diseases-CKD. Results: A total of 82 DM-patients, 50 males (61%) and 32 females (39%) with age mean (95% CI) of 50.8 (47.1 - 55.2) years for all patients, ranged between 15 to 65 years. Histological findings showed that 57.3% of patients had DN. While focal-segmental-glomerulosclerosis-FSGS was present in 20.7%—primary in 8.6% and secondary in 12.1%. IgA represented 4.9%, while Lupus nephritis, Membranous and drug induced interstitial nephritis were each present in 3.7%. MCD was present in 2.4%. Lastly diffuse proliferative GN, ANCA associated glomerulonephritis, and hypertensive nephrosclerosis accounted for 1.2%. Conclusion: The prevalence of NDKD is remarkably frequent in DM patients who underwent kidney biopsy and FSGS was the most frequent diagnosis. To get a proper histopathological diagnosis, an adequate tissue biopsy is needed with an adequate number of glomeruli. There is a great need for more consideration to biopsy diabetic patients, as the finding of NDKD requires a different therapeutic approach. This, hopefully, will help to manage these patients better and therefore, ameliorate the progression to ESKD over time and therefore delay the need for RRT.

Effects of Qidi Tangshen granules and their separate prescriptions on podocytes in mice with diabetic nephropathy

Objective:Previous studies have found that Qidi Tangshen granules(QDTS),a combination therapy of supplementing essence(Tianjing,TJ)and unblocking the collaterals(Tongluo,TL),can reduce kidney damage in db/db mice.This study aimed to explore the effect of QDTS and their separate prescriptions on podocytes in mice with diabetic nephropathy.Methods:The db/db mice were used in this experiment as an animal model,while wild-type C57BL/6J mice were used as normal controls.At the age of 12 weeks,the db/db mice were randomly divided into 5 groups(db/db,db/dbþvalsartan,db/dbþQDTS,db/dbþTJ and db/dbþTL).The urine albumin excretion ratio(UAE)was measured by enzyme-linked immunosorbent assay before and after the intervention.The ultrastructure of the kidney podocytes was observed by transmission electron microscopy.The protein expression levels of nephrin and desmin were detected by immunohistochemistry.Results:QDTS and their separate prescriptions significantly decreased the UAE and attenuated the renal pathological injury.QDTS and their separate prescriptions also reduced the fusion rate of the foot processes and increased the expression of nephrin protein.In contrast,QDTS and their separate prescriptions(TJ and TL)reduced the expression level of desmin protein.Conclusion:QDTS and their separate prescriptions might reduce diabetes-induced renal injury by reducing podocyte damage.The therapeutic effect of QDTS was more pronounced than TJ and TL.

EARLY CHANGES OF KIDNEY MORPHOLOGY AND FUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

In order to study the nephropathy associated with experimental streptozotocin diabetes, serial functional and ultrastructural studies were done in insulin-treated (Group T), untreated (Group D) diabetic Wistar rats and normal controls on d 3, d 8, d 14 and d 28 of diabetes. The ratio of kidney weight to the body weight (KW/BW) and mean glomerular diameter (MGD) in diabetes rats at varying durations were increased as compared with those in control animals, but an increase of KW/BW and MGD in Group D was more marked than in Group T. The creatinine clearance (Ccr) and total urinary protein excretion rate (TUPER) were increased in Group D end T, but the increase in TUPER appeared later in Group T than in Group D. Enlargement of epithelial cells, disappearance of folds on their surface and widening of foot processes were observed after 3 d of diabetes. After 14 d of diabetes, increased basement membrane-like material in the mesangium was found. Morphologically an increase in glomerular size, expanded foot processes with ball-like terminal expansions, thickened basement membrane were observed.

The Spectrum of Kidney Disease in Type Two Diabetic Patients: A Single-Center Study

Background: Diabetic nephropathy (DN) is the dominant reason for end-stage kidney disease linked with a rise in cardiovascular mortality rate. However, besides DN, type 2 diabetic patients may also suffer from various non-diabetic renal diseases (NDRD). Aim: The objective of the current research was to assess the occurrence and type of NDRD diagnosed by kidney biopsy in type 2 diabetic subjects, evaluate the association of various clinical and laboratory characteristics with histopathology findings, and identify essential predictors of NDRD. Methods: Retrospective analysis has been performed through medical record revision of 101 patients with type 2 diabetes undergoing percutaneous renal biopsy at Qilu Hospital of Shandong University (Jinan, China) between January 2015 and December 2020. Results: Renal biopsy results showed that NDRD was found in 59 patients (58.42%), while DN existed in 32 patients (31.68%) and 10 patients (9.90%) showed DN complicated with NDRD. Membranous nephropathy was prevailing NDRD (42%), followed by focal segmental glomerulosclerosis (11.6%) and IgA nephropathy (10.1%). In univariate analysis, patients with NDRD had older age (p Conclusions: Clinical parameters such as short duration of diabetes, older age, higher hemoglobin level, and lower proteinuria might be associated with NDRD in type 2 diabetic patients. An early diagnosis of NDRD poses a favorable renal prognosis because it requires a different approach than DN, further larger multicenter randomized prospective investigations focused on identifying possible risk markers of NDRD are still in priority.

LncRNA ZEB1-AS1和LncRNA SOX2OT在糖尿病肾病患者中的表达及与肾功能的相关性研究

目的探究长链非编码RNA锌指E盒结合同源盒蛋白1反义链1(LncRNA ZEB1-AS1)和长链非编码RNA性别决定相关基因簇2重叠转录本(LncRNA SOX2OT)在糖尿病肾病(DN)患者中的表达及与肾功能的相关性。方法选取于2021年11月—2023年12月在武汉大学人民医院肾内科收治的DN患者106例为DN组,并根据24 h尿蛋白定量(24 h Upro)水平分为正常蛋白尿亚组43例(<30 mg)、微量蛋白尿亚组39例(30~<300 mg)、大量蛋白尿亚组24例(≥300 mg),另选取同期医院单纯糖尿病患者106例作对照组,检测患者血清LncRNA ZEB1-AS1、LncRNA SOX2OT水平;Pearson法分析LncRNA ZEB1-AS1和LncRNA SOX2OT与肾功能指标的相关性;Logistic分析影响DN患者肾功能损伤的因素。结果DN组血清LncRNA ZEB1-AS1、LncRNA SOX2OT水平低于对照组(t=11.471、10.257,P均<0.001)。血清LncRNA ZEB1-AS1、LncRNA SOX2OT比较,正常尿蛋白亚组>微量尿蛋白亚组>大量尿蛋白亚组(F=58.720、117.722,P均<0.001),BUN、SCr、UA水平比较,正常尿蛋白亚组<微量尿蛋白亚组<大量尿蛋白亚组,差异均有统计学意义(F=122.493、595.589、53.178,P均<0.001);LncRNA ZEB1-AS1、LncRNA SOX2OT分别与BUN、SCr、UA呈负相关(r=-0.487、-0.498、-0.521,-0.527、-0.515、-0.534,P均<0.001);Logistic回归分析显示,糖尿病病程长及高BUN、SCr、UA水平是影响DN患者肾功能损伤的危险因素[OR(95%CI)=1.672(1.128~2.479)、2.839(1.534~5.253)、2.754(1.512~5.017)、2.693(1.464~4.954)],高LncRNA ZEB1-AS1、LncRNA SOX2OT是保护因素[OR(95%CI)=0.875(0.798~0.959)、0.898(0.832~0.969)]。结论血清LncRNA ZEB1-AS1、LncRNA SOX2OT水平与DN患者肾功能有关,可能是评估DN患者肾功能的潜在指标。

间充质干细胞对糖尿病肾病小鼠lncRNA的干预及肾脏保护的可能机制

目的 筛选糖尿病肾病(DN)小鼠模型中异常表达的长链非编码RNA(lncRNA),探索与间充质干细胞(MSC)干预可能的lncRNA是否对小鼠肾脏起保护作用及可能机制。方法 利用基因表达综合数据库(GEO)来源的转录组测序(RNAseq)数据,对DN小鼠RNAseq数据与正常小鼠进行筛选,得到与DN相关的lncRNA并进行验证,得到上调前3名的lncRNA,选取变化最显著的lncRNA进行下一步实验。分离培养小鼠肾小管上皮细胞(mRTECs)及骨髓间充质干细胞(BMSC),分组培养mRTECs[对照组、高糖(HG)组、HG+BMSC组],四甲基偶氮唑蓝(MTT)检测各组mRTECs细胞增殖率,荧光定量PCR法检测各组mRTECs中胶原蛋白(collagen)Ⅰ、α-平滑肌肌动蛋白(SMA)、波形蛋白(vimentin)、E-钙黏蛋白(cadherin) mRNA表达。采用siRNA敲减mRTECs中lncRNA的表达,构建正确的pcDNA3.1(+)质粒扩大培养。分组培养mRTECs(对照组、NC组、lncRNA组;si-NC组、si-lncRNA组、HG组、HG+si-lncRNA组;HG+BMSC组、HG+BMSC+lncRNA组),Western印迹检测各组细胞中collagenⅠ、α-SMA、vimentin、E-cadherin蛋白表达。结果 上调前3位的lncRNA为lncRNA NONMMUG023935、lncRNA NONMMUG030287、lncRNA NONMMUG004302。mRTECS经HG处理后,细胞增殖率、collagenⅠ、α-SMA和vimentin及lncRNA NONMMUG023935、lncRNA NONMMUG030287、lncRNA NONMMUG004302表达显著上升,E-cadherin表达显著下降(P<0.05)。而加入BMSC的mRTECs经HG处理后,上述指标的结果相反(P<0.05)。根据上述3个lncRNA表达变化绝对值最大选取lncRNA NONMMUG023935进行后续实验。转染si-lncRNA-NONMMUG023935后,相对应的lncRNA-NONMMUG023935表达显著降低(P<0.01)。lncRNA NONMMUG023935过表达可促进对mRTECs的损伤(P<0.05),BMSC可通过下调lncRNA NONMMUG023935表达从而抑制对HG诱导的mRTECs的损伤(P<0.05)。结论 MSC可下调DN肾小管上皮细胞中lncRNA NONMMUG023935的表达,从而改善肾脏纤维化,这可能是MSC延缓DN进展的机制之一。

尿常规蛋白尿定性检验在糖尿病肾病临床诊断中的应用

目的 探讨尿常规蛋白尿定性检验在糖尿病肾病诊断中的应用价值。方法 选择广东省茂名农垦医院2020年2月—2022年2月收治的54例糖尿病患者作为观察组,以同期在该院参加体检的54例健康体检者作为对照组。对参加研究的人员实施尿常规蛋白尿定性检验,比较两组尿糖、尿微量白蛋白、白细胞、白细胞酯酶的阳性检出率。根据年龄将观察组患者分为<30岁组(7例)、30~60岁组(19例)、> 60岁组(28例),比较不同年龄组糖尿病患者的蛋白尿(尿蛋白+~++和+++)检出情况。结果 观察组尿糖、尿微量白蛋白、白细胞、白细胞酯酶的阳性检出率均显著高于对照组(尿糖:90.91%比0%;尿微量白蛋白:100.00%比3.70%;白细胞:92.59%比9.26%;白细胞酯酶:96.30%比5.56%;均P <0.05)。<30岁组的尿蛋白+~++检出率最高,为57.14%;> 60岁组的尿蛋白+++检出率最高,为89.29%。不同年龄组的尿蛋白+++检出率比较差异有统计学意义。结论 在糖尿病肾病的诊断中应用尿常规蛋白尿定性检验的临床价值较高,且可得出年龄与糖尿病肾病发生具有一定关系的结论。

中医运用王氏肾炎汤治疗糖尿病肾病经验

本文主要介绍了王玉林老中医结合中医基础、内科理论及吸取了少数民族民间药物应用经验,来治疗糖尿病肾病。王玉林名老中医总结糖尿病肾病主要与脾肾关系最为密切,常与先天脾肾不足以及后天耗损有关,兼有湿邪、痰浊、淤血因素。王老通过长期临床经验总结糖尿病肾病病因,分析病机,辨证施治,同时辅以其经验用药,常常在临床上取得满意的疗效。在长期临床中,接诊很多因长期血糖控制不佳最终发展为糖尿病肾病患者,王老善于辨证论治,用中药整体治疗,并总结自己经验用药,自拟为王氏肾炎汤,主要用于以脾肾气虚型为主的慢性肾炎、糖尿病肾病所引起的水肿、蛋白尿等症,本文总结王玉林名老中医治疗诊治糖尿病肾病经验。

尿毒清颗粒联合缬沙坦胶囊治疗糖尿病肾病大量蛋白尿的临床研究

目的 探究尿毒清颗粒联合缬沙坦胶囊在糖尿病肾病患者大量蛋白尿治疗中的临床效果。方法 选取2020年5月—2023年6月江苏省盱眙县人民医院肾内科收治的64例血肌酐在108~265μmol/L的糖尿病肾病合并大量蛋白尿患者为研究对象,根据抛硬币法分为对照组和研究组,均接受常规降糖药物二甲双胍治疗,对照组(n=32)采用钠-葡萄糖协同转运蛋白2抑制剂治疗,研究组(n=32)采用缬沙坦联合尿毒清颗粒治疗。连续30 d治疗后,比较两组治疗效果。结果 研究组治疗总有效率为93.75%,高于对照组的71.88%,差异有统计学意义(χ^(2)=5.379,P<0.05);研究组的24 h尿微量蛋白、24 h尿蛋白定量、血肌酐、血尿素氮水平均优于对照组,差异有统计学意义(P均<0.05);研究组空腹血糖和餐后2 h血糖水平均低于对照组,差异有统计学意义(P均<0.05)。结论 尿毒清颗粒配合缬沙坦胶囊可改善糖尿病肾病大量蛋白尿和肾功能指标,提高临床治疗有效性,保证患者用药后获取理想疗效。

达格列净联合血管紧张素转换酶抑制剂在糖尿病肾病蛋白尿患者临床治疗中的应用效果分析

目的分析达格列净联合血管紧张素转换酶抑制剂在糖尿病肾病蛋白尿患者临床治疗中的应用效果。方法选取睢宁县人民医院于2021年1月—2023年3月收治的78例糖尿病肾病患者作为研究对象,根据随机数表法将其分为两组,均给予控糖治疗。对照组(n=38)给予血管紧张素转换酶抑制剂治疗(盐酸贝那普利片),观察组(n=40)在对照组治疗基础上联合达格列净治疗。比较两组患者治疗前后尿微量蛋白(Urine Microprotein,mALB)、24 h尿蛋白定量、血清白蛋白(Albumin,ALB)水平、血糖水平以及并发症发生情况。结果治疗后,观察组mALB[(167.12±23.15)mg/L]、24 h尿蛋白定量[(1.04±0.28)g/24 h]均低于对照组[(342.52±35.26)mg/L、(1.72±0.62)g/24 h],差异有统计学意义(P均<0.05);血清ALB水平[(33.74±1.16)g/L]高于对照组(31.93±0.85)g/L,差异有统计学意义(P<0.05)。治疗后,观察组的空腹血糖[(5.16±1.67)mmol/L]低于对照组[(6.69±2.24)mmol/L],餐后2h血糖[(6.59±2.05)mmol/L]低于对照组[(8.76±3.25)mmol/L],糖化血红蛋白[(4.35±1.86)%]低于对照组[(6.26±2.85)%],差异有统计学意义(t=3.432、3.546、3.522,P均<0.05)。观察组并发症发生率低于对照组,差异有统计学意义(P<0.05)。结论在糖尿病肾病蛋白尿患者的临床治疗中,达格列净联合血管紧张素转换酶抑制剂的应用效果较为显著。

糖尿病肾病患者血清lncRNA NEAT1、miR-23c水平与病情进展的关系

目的探讨糖尿病肾病患者血清长链非编码RNA(lncRNA)核丰富转录本1(NEAT1)、微小RNA miR-23c水平与糖尿病肾病(DN)病情进展的关系。方法将该院2019年5月至2020年5月收治的136例DN患者纳入研究作为DN组。另选取58例同期于该院进行体检的健康者作为对照组。采用实时荧光定量PCR(qPCR)检测两组受试者血清lncRNA NEAT1、miR-23c、肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关载脂蛋白(NGAL)、肿瘤坏死因子-α(TNF-α)mRNA、白细胞介素-6(IL-6)mRNA水平。采用Pearson/Spearman相关分析DN患者血清lncRNA NEAT1、miR-23c与KIM-1、NGAL、TNF-α、IL-6 mRNA水平及eGFR的相关性。对DN患者进行CKD分期,比较不同CKD分期患者血清lncRNA NEAT1、miR-23c和KIM-1、NGAL、TNF-α、IL-6 mRNA水平,采用多元有序Logistic回归分析血清lncRNA NEAT1、miR-23c水平是否为DN病情进展的影响因素。结果与对照组比较,DN组血清lncRNA NEAT1和KIM-1、NGAL、TNF-α、IL-6 mRNA水平升高,miR-23c、估算的肾小球滤过率(eGFR)降低,差异均有统计学意义(P<0.05)。G1~G5期DN患者血清lncRNA NEAT1和KIM-1、NGAL、TNF-α、IL-6 mRNA水平均依次升高,miR-23c水平依次降低(P<0.05)。DN患者血清lncRNA NEAT1与KIM-1、NGAL、TNF-α、IL-6 mRNA水平呈正相关(P<0.05),与miR-23c、eGFR呈负相关(P<0.05);血清miR-23c水平与KIM-1、NGAL、TNF-α、IL-6 mRNA水平呈负相关(P<0.05),与eGFR呈正相关(P<0.05)。lncRNA NEAT1(OR=2.177,95%CI:2.113~2.441)为DN病情进展的独立危险因素,miR-23c(OR=0.595,95%CI:0.543~0.726)为独立保护因素(P<0.05)。结论DN患者血清lncRNA NEAT1水平的升高及miR-23c水平的降低均与DN病情进展密切相关。

当归补血汤联合回旋灸对CKD 3—5期非透析糖尿病肾病合并肾性贫血的临床研究

目的:探讨当归补血汤联合回旋灸对慢性肾脏病(CKD)3—5期非透析糖尿病肾病合并肾性贫血患者肾小球滤过功能,血管钙化、肠源性内毒素水平及铁调素-25(hepcidin-25)、β-羟丁酸(β-HB)的影响。方法:研究对象为2021年12月至2023年2月于该院肾内科就诊的CKD 3—5期非透析糖尿病肾病合并肾性贫血患者102例,根据随机数字表法分为研究组和对照组,各51例。在常规治疗(控制饮食、适量运动、口服罗沙司他)基础上,对照组患者给予回旋灸治疗,研究组患者在对照组的基础上服用当归补血汤,两组患者均连续治疗3个月。治疗结束后统计两组患者的疗效,比较两组患者肾小球滤过功能、血管钙化评分,外周血内毒素(LPS)、白细胞介素6(IL-6)、hepcidin-25和β-HB水平。结果:研究组患者的总有效率为96.08%(49/51),明显较对照组的84.31%(43/51)更高,差异有统计学意义(P<0.05)。相较于对照组,研究组患者治疗后肾小球滤过率估计值更高,腹主动脉血管钙化程度评分更低,外周血中LPS、IL-6、hepcidin-25和β-HB水平更低,外周血中血红蛋白、铁蛋白、转铁蛋白饱和度和转铁蛋白水平更高,差异均有统计学意义(P<0.05)。结论:对于CKD 3—5期非透析糖尿病肾病合并肾性贫血患者,当归补血汤联合回旋灸改善贫血的疗效较好,且可提高肾小球滤过功能,减轻血管钙化程度,其作用机制可能与降低肠源性内毒素水平、调节hepcidin-25和β-HB水平有关。

血清non-HDL-C与2型糖尿病肾病关系的临床研究

目的探讨血清非高密度脂蛋白胆固醇表达水平与2型糖尿病肾病的相关性。方法选择我院收治的2型糖尿病患者187例作为研究对象,按照是否合并糖尿病肾病分为无肾病组50例,早期肾病组49例,肾病组51例以及晚期肾病组37例;另选择同期于我院进行健康体检且各项检查均正常的体检者50例作为正常对照组。检测各组总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,计算非高密度脂蛋白胆固醇(non-HDL-C)含量,并进行组间比较,采用多项分类Logistic回归分析。结果在糖尿病患者中,TC、TG、LDL-C以及non-HDL-C均随糖尿病肾病的进展而逐渐升高,HDL-C随疾病进展而逐渐下降,组间均有统计学差异(P<0.05)。以正常对照组为参考分类,无肾病组血清non-HDL-C的优势比略强于TG,并且明显强于其他项目。而在其他3组中,non-HDL-C的优势比显著强于其他项目,且随着肾病进展而呈现优势比明显增加趋势。结论血清non-HDL-C水平是反映2型糖尿病肾病发生及进展的可靠指标,且较其他血脂指标更加灵敏,检测此指标有助于病情进展的判断和治疗效果的评价。

Intensive Antihypertensive Treatment with Angiotensin Receptor Blocker Combined with Hydrocholorthiazide Reduces Urinary Angiotensinogen in Patients with Type 2 Diabetes Mellitus

Purpose: Local activation of rennin-angiotensin system (RAS) is involved in the progression of chronic kidney disease (CKD). One of the RAS components, angiotensinogen (AGT) has been known to be a potential surrogate biomarker for the renal RAS activity. Measuring the daily urinary excretion of AGT (U-AGT), the present study addressed whether the intensive blood pressure (BP) lowering with combined antihypertensive agents could improve such an abnormality in diabetic CKD patients. Methods: Uncontrolled hypertensive patients with type 2 diabetes with mild to moderate nephropathy previously receiving angiotensin receptor blockers (ARB) in an optimal dose alone were recruited for a better blood pressure (BP) control. Urinary specimens were subjected to a quantitative measurement of a daily urinary protein (U-prot) and U-AGT. After the baseline measurement, intensive antihypertensive therapy was attempted by switching the ARB dose to a fixed combination formula of candesartan 8 mg plus hydrochlorthiazide (HCTZ) 6.25 mg and the patients were followed up for 24 weeks. Comparison of parameters was then made between the values at the baseline and the end of the study. Results: At baseline, there was a significant positive correlation between U-AGT and U-prot, and between U-AGT and serum creatinine (Cr) concentration. In addition, U-AGT was inversely correlated with estimated glomerular filtration rate (e-GFR). Switching the antihypertensive regime from ARB alone to the combined ARB/HCTZ significantly reduced BP, U-AGT and U-prot. The magnitude of the reduction in U-prot was positively correlated with that in U-AGT. A stepwise regression analysis showed that HbA1c, e-GFR and the reduction in U-prot in response to the intensive antihypertensive therapy were positively correlated with the reduction in U-AGT. Conclusion: U-AGT is increased and positively correlated with U-prot in patients with type 2 diabetic nephropathy. Intensive antihypertensive treatment with ARB combined with HCTZ reduces both U-AGT and U-prot, presumably via an amelioration of an accelerated renal RAS activity. These data also suggest that U-AGT can be used as a potential therapeutic surrogate biomarker for the activated renal RAS in patients with diabetic nephropathy.