mTOR inhibitor everolimus ameliorates progressive tubular dysfunction in chronic renal failure rats

Responsible factors in progressive tubular dysfunction in chronic renal failure have not been fully identified. In the present study, we hypothesized that the mammalian target of rapamycin, mTOR, was a key molecule in the degenerative and progressive tubular damage in chronic renal failure. Everolimus, an mTOR inhibitor, was administered for 14 days in 5/6 nephrectomized (Nx) rats at 2 and 8 weeks after renal ablation. Marked activation of the mTOR pathway was found at glomeruli and proximal tubules in remnant kidneys of Nx rats. The reduced expression levels of the phosphorylated S6 indicated the satisfactory pharmacological effects of treatment with everolimus for 14 days. Everolimus suppressed the accumulation of smooth muscle alpha actin, infiltration of macrophages and expression of kidney injury molecule-1 in the proximal tubules. In addition, everolimus-treatment restored the tubular reabsorption of albumin, and had a restorative effect on the expression levels of membrane transporters in the polarized proximal tubular epithelium, when its administration was started at 8 weeks after Nx. These results indicate that the constitutively activated mTOR pathway in proximal tubules has an important role in the progressive tubular dysfunction, and that mTOR inhibitors have renoprotective effects to improve the proximal tubular functions in end-stage renal disease.     

Lipoprotein (a) and microvascular disease in type 1 (insulin-dependent) diabetes.

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.     

Ambulatory Blood Pressure and Endothelial Dysfunction in Hematopoietic Cell Transplantation Recipients

Hematopoietic cell transplantation (HCT) is a common treatment for many disorders. Albuminuria post-HCT, which may represent endothelial injury or inflammation from graft- versus-host disease, increases the risk of chronic kidney disease and nonrelapse mortality at 1 year. HCT recipients also have abnormal blood pressure (BP) and increased rates of cardiovascular complications. We sought to determine the relationships among albuminuria, endothelial dysfunction, and BP in HCT recipients. Patients age ?≥12 years who underwent their first allogeneic HCT between 2012 and 2015 and survived through day 80 post-HCT were eligible. Peripheral endothelial function was assessed using the EndoPAT2000 device at day 80 along with 24-hour ambulatory BP monitoring (ABPM). Clinical and laboratory data were collected along with a urine sample for calculation of the albumin-to-creatinine ratio. Both logistic and linear regression analyses were used to identify associations between EndoPAT score and clinical variables. Sixty patients (median age, 48 years; range, 14 to 69 years) completed the study. The median EndoPAT score was 2.05 (range, 1.02 to 4.45), and 17 patients (28%) had abnormal endothelial function. Forty-two patients (72%) had ambulatory hypertension (HTN), and 38 (63%) had blunted nocturnal dipping. HTN on ABPM (P?=?.045) and blunted nocturnal dipping (P?=?.04) were associated with a lower EndoPAT score. Albuminuria was not associated with EndoPAT score. There was a lack of agreement between our clinical definition of HTN (office BP and/or use of medications) and ABPM results (P?=?.04). We did not find an association between lower EndoPAT scores and albuminuria, but did find an association between an abnormal nocturnal dip and HTN diagnosed by ABPM. This suggests that albuminuria may reflect local endothelial injury and inflammation rather than a systemic process. Office BP readings do not accurately reflect true BP, suggesting that 24-hour ABPM studies are needed to diagnose and treat HTN appropriately.     

培哚普利对伴微量白蛋白尿老年高血压者的肾脏作用

对１４例伴微量白蛋白尿老年高血压患者应用血管紧张素转换酶抑制剂（ＡＣＥＩ）—培哚普利，短期观察２个月，结果显示：２个月后，２４小时尿白蛋白排泄显著降低（Ｐ＜０．０５），平均动脉压亦显著降低（Ｐ＜０．０５），但两者的下降无显著相关；研究期间，血肌酐、尿素氮及血钾无明显变化。资料提示：培哚普利可降低老年高血压患者尿白蛋白排泄，可能对防治高血压肾脏病变有一定作用，该作用不完全依赖于血压的降低。     

高血压病患者尿微量白蛋白与血浆高敏C反应蛋白的关系

目的:探讨高血压病患者尿微量白蛋白(UMA)与血浆高敏C反应蛋白(hs-CRP)之间的关系。方法:选择高血压病患者48例和健康对照者45例,高血压患者又根据UMA水平分为UMA异常组(UMA≥20mg/L)和UMA正常组(UMA20mg/L),常规测量血压、体重、身高、计算体重指数(BMI),并抽取空腹静脉血检测血糖、血脂、hs-CRP。结果:高血压病组hs-CRP水平显著高于正常对照组[(1.68±0.48)mg/L:(0.57±0.20)mg/L,P0.01];高血压患者中UMA异常组血浆hs-CRP水平显著高于UMA正常对照组[(2.41±0.50)mg/L:(2.01±0.47)mg/L,P0.01];UMA与hs-CRP水平呈正相关(r=0.392,P0.05)。结论:高血压患者高敏C反应蛋白水平升高可能参与尿微量白蛋白的发生,提示高血压可能通过炎症反应加重内皮功能的损害。     

白蛋白尿对中老年人群总死亡及心血管病死亡的预测研究

目的 了解中老年人群白蛋白尿与总死亡及心血管病死亡之间是否有独立关系。 方法 在北京市首钢社区整群随机选取40岁以上人群2500人,实际调查2315人。收集清晨首次尿标本,测量尿白蛋白和肌酐,计算尿白蛋白/肌酐比（ACR）。以ACR<30、30~299、 ≥300 mg/g分为正常、微量、显性白蛋白尿3组。微量、显性组合称白蛋白尿组。同时调查心血管病危险因素。4年后对该人群进行随访,共获得1725人的结局事件。使用Cox回归模型调整混杂因素,分析白蛋白尿与死亡的关系。 结果 研究人群中微量、显性白蛋白尿的患病率分别为7.6%和1.4%。4年后随访结果显示,正常、微量、显性组心血管病死亡事件发生率分别为2.7/1000人年、19.9/1000人年和11.5/1000人年,总死亡发生率分别为6.6/1000人年、25.9/1000人年和57.5/1000人年。调整混杂因素后,与正常组相比,白蛋白尿组发生心血管病死亡的风险（hazard ratio,HR）为5.26（95%CI 2.26~12.24）,发生总死亡的HR为3.34（95%CI 1.82~6.15）。在无心血管病史的人群中,白蛋白尿患者发生心血管病死亡和总死亡的风险分别为6.92（95%CI 1.80~26.58）和2.85（95%CI 1.22~6.65）。 结论 首钢社区中老年人群中,白蛋白尿是心血管病死亡和总死亡发生的独立预测因素。     

上海市社区2型糖尿病患者清蛋白尿的患病情况及相关危险因素调查

目的了解上海市社区糖尿病人群清蛋白尿的患病情况及相关危险因素。方法选择上海市社区卫生服务机构管理的2型糖尿病患者,收集患者的临床资料(包括人口学资料和实验室检查结果),根据尿清蛋白/尿肌酐比值(ACR)来评价糖尿病患者的清蛋白尿情况。结果共调查了2 044例患者,其中男性852例,女性1 192例,平均年龄(67.6±9.6)岁。微量清蛋白尿占22.7%,临床清蛋白尿占5.0%。糖尿病患者中清蛋白尿的患病率随着年龄、糖化血红蛋白和病程的增长而增高。Logistic回归分析显示,年龄≥80岁、高血压、糖化血红蛋白≥7%和三酰甘油(TG)水平是糖尿病患者发生微量清蛋白尿的独立危险因素;病程≥10年、高血压和总胆固醇(TC)水平是糖尿病患者发生临床清蛋白尿的独立危险因素,高密度脂蛋白胆固醇(HDL-C)则是糖尿病患者避免发生临床清蛋白尿的保护因素。结论上海市社区糖尿病患者中清蛋白尿的患病率较高,糖尿病肾病可能与血压、体质量、血脂和血糖相关,提示降低血压、控制体质量、控制血脂和血糖对预防和治疗糖尿病肾病有着很大的重要性。     

螺内酯对2型糖尿病肾病患者尿清蛋白的影响

目的探讨螺内酯对2型糖尿病肾病患者尿清蛋白的影响。方法选取86例合并Ⅲ期糖尿病肾病的2型糖尿病患者,将其随机分为试验组(44例)和对照组(42例)。对照组采用常规治疗,试验组在常规治疗基础上加用螺内酯20 mg/d,治疗12周。分别观察治疗前后两组患者血压、血糖[空腹血糖(FBG)、餐后2 h血糖(2 hP-BG)]、血脂[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)]、糖化血红蛋白(HbA1c)、尿清蛋白/尿肌酐(ACR)、血电解质(钾、钠)、血肌酐(SCr)等。结果对照组和试验组分别有38例和40例完成研究。两组患者治疗前及治疗后FBG、2 hPBG、收缩压、舒张压、HbA1c、TG、LDL-C、SCr比较,差异均无统计学意义(P>0.05)。对照组患者治疗后ACR与治疗前比较[(110±111)mg/g与(82±68)mg/g],差异无统计学意义(P>0.05);而试验组患者治疗后ACR较治疗前显著降低[(45±47)mg/g与(85±59)mg/g],也显著低于对照组治疗后,差异均有统计学意义(P<0.05)。两组患者治疗后血清TC水平均较治疗前显著降低,差异有统计学意义(P<...     

蹲踞试验对糖尿病心血管自主神经病变的诊断价值——附66例分析

目的：评价蹲踞试验对糖尿病心血管自主神经病变的诊断价值。方法：对６６例２型糖尿病患者和４４名正常对照组同期进行蹲踞经典心电图心血管自主神经功能测定。结果 与对照组同年龄比较，糖尿病踞副交感神经功能比值（ＳｑＴｖ）明显升高，蹲踞交感神经功能比值（ＳｑＴａ）显著降低；与对照组和正常清蛋白尿患者比较，伴清蛋水者，尤其是大量清蛋白尿者。ＳｑＴｖ明显升高，ＳｑＴｓ明显降ｑＴｖ和ＳｑＴｓ和经典心血管自主神经功