The angiotensin II receptor-neprilysin inhibitor LCZ696 attenuates the progression of proteinuria in type 2 diabetic rats

We examined the effects of the angiotensin receptor-neprilysin inhibitor LCZ696 on overt proteinuria and renal injury in type 2 diabetic Otsuka-Long- Evans-Tokushima-Fatty (OLETF) rats. Aged OLETF rats were also treated with either valsartan or valsartan plus hydralazine for comparison. LCZ696 caused greater attenuation of the progression of proteinuria than either valsartan alone or valsartan combined with hydralazine. Reduced glomerular injury and tubulointerstitial fibrosis were also observed in LCZ696-treated rats. Moreover, LCZ696 prevented increases in blood urea nitrogen (BUN) and creatinine levels. These data suggest that LCZ696 elicits a reno-protective effect against type 2 diabetes with overt proteinuria.     

Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients

This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group. The correlation coefficient between PCX and ACR, and the odds ratio of PCX were gauged in the study. Area under the receiver operating characteristic (ROC) curve was also calculated. There were 188 patients in the normal group with urine ACR < 30 mg/g, and 132 patients in the microproteinuria group with urine ACR 30–300 mg/g. 132 cases of DKD diagnosed with ACR, among them, 104 cases of DKD were predicted by PCX. The percentage correction value was 78.8%. The following parameters such as gender, age, course of disease, glycated hemoglobin, triglyceride, total cholesterol, BMI, blood pressure, uric acid, and eGFR were used as variables for adjustment to establish the prediction model of urine PCX and ACR. Multiple logistic regression test was carried out to evaluate against the predictive ability of the model. The area under the ROC curve corresponding to the regression model after adjustment is 0.952. Although factors such as the course of disease, HbA1C, UA, and eGFR could influence on the predictive ability of PCX, PCX still has a good ability to predict early DKD in older patients. Therefore, it could be used as a diagnostic indicator for early-stage DKD in older patients.     

Sodium-glucose cotransporter 2 inhibitors as the first universal treatment of chronic kidney disease

In the last five years, the medical community was astonishingly surprised by the sequential large outcome trials that displayed the renal effects of sodium glucose co-transporter inhibitors (SGLT2Is) in type 2 diabetes mellitus (T2DM) patients with or without chronic kidney disease (CKD). This favorable effect was later disclosed in non-diabetic CKD patients. The EMPA-REG OUTCOME trial was the first trial that showed a reduction for the need for dialysis in patients suffering diabetic kidney disease (DKD) by 55%. This figure is double the score achieved by the angiotensin receptor blocker, Losartan, in RENAAL trial. The need for dialysis in DAPA-CKD trial was reduced in diabetic and non-diabetic CKD patients by 33%. The renal-specific composite outcome was reduced by 39% in EMPA-REG trial, 40% in CANVAS study, 47% in DECLARE-TIMI 58 study, 34% in CREDENCE trial, and 44% in DAPA-CKD trial. The greater surprise is the significant favorable effect of SGLT2Is on overall mortality in CKD patients with or without T2DM. Similar survival benefit was not previously encountered with any of the medications used in CKD patients with or without diabetes. In this review, we disclose the results of the DAPA-CKD trial, the CREDENCE trial and those of several cardiovascular outcome trials (CVOT) that used different SGLT2Is and showed that patients with lower eGFR levels may have greater benefit with respect to cardiovascular morbidity than patients with normal kidney function. In addition, we discuss the different mechanisms of action that explain the renal beneficial effects of SGLT2Is.     

糖尿病肾病代谢组学差异代谢物的研究进展

糖尿病肾病是糖尿病主要的慢性微血管并发症之一,也是引起终末期肾病最常见的原因。糖尿病肾病代谢组学通过研究内源性代谢物产生的变化性和规律性,寻找新的诊断指标,并为糖尿病肾病的早期诊断和机制研究提供了新思路。综述近十年来糖尿病肾病代谢组学的差异代谢物研究现状,并从差异代谢物的检出频次、样本分布、类别及生物学意义方面进行了深入分析,以期促进糖尿病肾病病理机制更广泛而深入的研究。     

Bilirubin and its changes were negatively associated with diabetic kidney disease incidence and progression: A five-year's cohort study based on 5323 Chinese male diabetic patients

Aims

This study aimed to evaluate the association between baseline bilirubin (TBiL) and follow-up TBiL changes for diabetic kidney disease (DKD) incidence and progression based on a 5?years' cohort study.

二肽基肽酶-4抑制剂在糖尿病肾病治疗中的研究进展

糖尿病肾病(DKD)是糖尿病的严重并发症之一,亦是世界范围内导致终末期肾病的最常见原因。二肽基肽酶-4(DPP-4)抑制剂是以降低血糖为初衷而研发,由于DPP-4多样化的生物学特征,DPP-4抑制剂(DPP-4is)超越降低血糖以外的多效性肾脏保护的机制也不断被挖掘。越来越多的动物及临床研究证实DPP-4is可以改善DKD临床表现与组织病理,在DKD治疗中发挥重要的作用。但与安慰剂相比,DPP-4is在大规模临床研究中证实了非劣效性,而不是真正的肾保护功效。本文就DPP-4is在糖尿病肾病治疗中的研究进展进行综述。     

益肾泄浊方联合缬沙坦治疗糖尿病肾病的临床观察

目的观察益肾泄浊方联合缬沙坦治疗糖尿病肾病的临床疗效。方法将68例糖尿病肾病患者随机分为对照组和治疗组,每组34例。对照组予基础治疗加缬沙坦口服,治疗组在对照组基础上加用益肾泄浊方。两组疗程均为12周,观察两组临床疗效,比较中医证候积分、血肌酐、肾小球滤过率、尿微量白蛋白、纤维蛋白原、D-二聚体水平的变化情况。结果①试验期间脱落及剔除8例,最终纳入统计60例,其中对照组31例、治疗组29例。②治疗组、对照组临床总有效率分别为86.2%和71.0%;组间临床疗效比较,治疗组优于对照组(P0.05)。③治疗前后组内比较,两组中医证候积分均明显降低(P0.05);组间治疗后比较,治疗组中医证候积分明显低于对照组(P0.05)。④治疗前后组内比较,两组血肌酐、尿微量白蛋白水平明显降低,肾小球滤过率明显升高(P0.05);组间治疗后比较,治疗组血肌酐、肾小球率过滤、尿微量白蛋白均较对照组明显改善(P0.05)。⑤治疗前后组内比较,治疗组纤维蛋白原、D-二聚体水平均明显下降(P0.05),对照组纤维蛋白原、D-二聚体无明显变化(P0.05);组间治疗后比较,治疗组纤维蛋白原、D-二聚体水平均明显低于对照组(P0.05)。结论益肾泄浊方联合缬沙坦治疗糖尿病肾病的临床疗效优于单用缬沙坦,能有效降低患者的尿蛋白,改善肾脏微循环及肾功能,同时能有效缓解患者的临床症状。     

脉络学说指导下津力达联合通心络治疗2型糖尿病肾病的临床观察

目的:观察脉络学说指导下津力达颗粒联合通心络胶囊治疗2型糖尿病肾病的临床疗效。方法:将120例2型糖尿病肾病患者随机分为对照组和治疗组,各60例,对照组予常规降糖降压等对症支持治疗,治疗组在对照组治疗基础上加津力达颗粒,1袋/次,3次/日,通心络胶囊4粒,3次/日,12周为1个疗程,治疗前后观察并比较两组患者的临床疗效、中医证候积分;糖代谢指标空腹血糖(FBG),餐后2 h血糖(2 h PG),糖化血红蛋(Hb A1c),胰岛素抵抗指数(HOMA-IR);脂代谢指标甘油三酯(TG),胆固醇(TC),低密度脂蛋白(LDL-C),高密度脂蛋白(HDL-C);肾功能血肌酐(SCr),尿白蛋白排泄率(UAER),尿β2微球蛋白(Uβ2-MG);甲襞微循环。结果:(1)对照组、治疗组临床总有效率分别为61. 67%,80. 00%,治疗组明显优于对照组(P 0. 05)。(2)中医证候积分改善比较,治疗组优于对照组(P 0. 05)。(3)治疗后治疗组在糖代谢指标FBG,2 h PG,Hb A1c上与对照组无明显差异,HOMA-IR改善优于对照组(P 0. 05);脂代谢指标TG,TC,LDL-C均明显降低(P 0. 05),HDL-C升高(P 0. 05);肾功能指标SCr,UAER,尿Uβ2-MG改善较对照组明显(P 0. 05);甲襞微循环结果显示,治疗组较对照组微循环改善明显(P 0. 05)。结论:通心络联合津力达可改善2型糖尿病肾病患者的临床症状,降低尿微量白蛋白,其机制可能与降糖、调节脂质代谢、改善微循环有关。