慢性肾脏病患者尿血管紧张素原与肾脏肾素血管紧张素系统活性的相关性

Objective To analyze the correlation of urinary angiotensinogen (AGT) with clinical index of kidney injury and intrarenal renin-angiotensin system (RAS) activity in chronic kidney disease (CKD) patients. Methods Urinary or plasma renin activity, AGT, angiotensin Ⅱ (Ang Ⅱ ), aldosterone were measured by RIA or ELISA in 129 CKD patients. Expression of intrarenal renin, AGT, Ang Ⅱ and angiotensinⅡ receptor was examined by immunohistochemistry staining (IHCS) in 73 CKD patients undergoing renal biopsy. Correlation of urinary AGT with other indexes was performed. Results Average urinary AGT in 129 CKD patients was (159.08 ± 125.18) μg/g Cr, Scr was (113.20± 105.05)μmol/L, and urinary AGT was positively correlated with Scr (r=0.51, P<0.01). Average estimated glomerular filtration rate (eGFR) was (58.52±27.15) ml·min-1·(1.73 m2)-1, which was negatively correlated with urinary AGT (r=-0.55, P<0.01). Average urinary protein was (2.03±2.65) g/24 h, which was positively correlated with urinary AGT (r=0.30, P<0.01). Average urinary Ang Ⅱ was (164.71 ±139.25) ng/g Cr, which was positively correlated with urinary AGT (r=0.20, P<0.05). Average urinary type Ⅳ collagen was (447.60± 800.66) μg/g Cr, which was positively correlated with urinary AGT (r=0.47, P<0.01). Average urinary soduim was (162.17±81.61) mmol/24 h, which was negatively correlated with urinary AGT (r=-0.20, P<0.05). Multiple regression analysis indicated that low eGFR (P<0.01), high Scr (P< 0.01), high urinary protein (P<0.05), high urinary Ang Ⅱ (P<0.05) and high urinary type Ⅲ collagen (P<0.01) were significantly correlated with high urinary AGT. In renal tissues of CKD patients, there was positive correlation of urinary AGT with positive IHCS area of AGT (r=0.45, P< 0.01), Ang Ⅱ (r=0.52, P<0.01) and angiotensin Ⅱ type 1 receptor (r =0.28, P <0.05). Conclusions Urinary AGT level may indicate the kidney injury severity, especially in chronic kidney injury, and may be used as a non-invasive marker of intrarenal Ang Ⅱ activity in CKD patients.     

慢性肾脏病患者尿血管紧张素原与肾脏肾素血管紧张素系统活性的相关性

Objective To analyze the correlation of urinary angiotensinogen (AGT) with clinical index of kidney injury and intrarenal renin-angiotensin system (RAS) activity in chronic kidney disease (CKD) patients. Methods Urinary or plasma renin activity, AGT, angiotensin Ⅱ (Ang Ⅱ ), aldosterone were measured by RIA or ELISA in 129 CKD patients. Expression of intrarenal renin, AGT, Ang Ⅱ and angiotensinⅡ receptor was examined by immunohistochemistry staining (IHCS) in 73 CKD patients undergoing renal biopsy. Correlation of urinary AGT with other indexes was performed. Results Average urinary AGT in 129 CKD patients was (159.08 ± 125.18) μg/g Cr, Scr was (113.20± 105.05)μmol/L, and urinary AGT was positively correlated with Scr (r=0.51, P<0.01). Average estimated glomerular filtration rate (eGFR) was (58.52±27.15) ml·min-1·(1.73 m2)-1, which was negatively correlated with urinary AGT (r=-0.55, P<0.01). Average urinary protein was (2.03±2.65) g/24 h, which was positively correlated with urinary AGT (r=0.30, P<0.01). Average urinary Ang Ⅱ was (164.71 ±139.25) ng/g Cr, which was positively correlated with urinary AGT (r=0.20, P<0.05). Average urinary type Ⅳ collagen was (447.60± 800.66) μg/g Cr, which was positively correlated with urinary AGT (r=0.47, P<0.01). Average urinary soduim was (162.17±81.61) mmol/24 h, which was negatively correlated with urinary AGT (r=-0.20, P<0.05). Multiple regression analysis indicated that low eGFR (P<0.01), high Scr (P< 0.01), high urinary protein (P<0.05), high urinary Ang Ⅱ (P<0.05) and high urinary type Ⅲ collagen (P<0.01) were significantly correlated with high urinary AGT. In renal tissues of CKD patients, there was positive correlation of urinary AGT with positive IHCS area of AGT (r=0.45, P< 0.01), Ang Ⅱ (r=0.52, P<0.01) and angiotensin Ⅱ type 1 receptor (r =0.28, P <0.05). Conclusions Urinary AGT level may indicate the kidney injury severity, especially in chronic kidney injury, and may be used as a non-invasive marker of intrarenal Ang Ⅱ activity in CKD patients.     

肾素-血管紧张素系统阻断与肾脏病

通过介绍血管紧张素Ⅱ（ＡⅡ）的产生途径、受体亚型等有关进展,比较阻断肾素血管紧张素系统不同方法的异同,探讨ＡⅡ１型受体拮抗剂（ＡＴ１ＲＡ）在降低血压及延缓肾脏疾病进展中的作用     

肾素—血管紧张素系统阻断与肾脏病

通过介绍血管紧张素Ⅱ（ＡⅡ）的产生途径、受体亚型等有关进展比较阻断肾素血管紧张素系统不同方法的异同。探讨了ＡⅡⅠ型受体拮抗剂（ＡＴＩＲＡ）在降低血压及延缓肾脏疾病进展中的作用。     

原发性IgA肾病患者肾脏局部血管紧张素Ⅱ表达与肾脏纤维化相关

目的 研究原发性IgA肾病患者肾脏局部肾素-血管紧张素系统（RAS）组分的表达及其相互调节,探讨肾内血管紧张素Ⅱ（AngⅡ）表达与临床病理损伤指标间的关系。 方法 采用免疫组织化学方法评价肾脏局部RAS组分的表达。分析36例原发性IgA肾病患者肾脏局部RAS组分表达之间的相关性以及肾内AngⅡ表达与血压、估算肾小球滤过率（eGFR）、24 h尿蛋白量和Katafuchi肾脏病理评分之间的相关性。 结果 肾内肾素、血管紧张素原与AngⅡ表达呈正相关（r ＝ 0.43,P < 0.01;r ＝ 0.34,P < 0.05）。肾内AngⅡ表达与eGFR呈负相关（r ＝ -0.61,P < 0.01）,并与病理慢性积分及间质炎性细胞浸润积分呈正相关（ρ ＝ 0.39,P < 0.05;ρ ＝ 0.52,P < 0.05）。 结论 IgA肾病患者肾内AngⅡ表达与肾内肾素、血管紧张素原表达相关,并且肾内AngⅡ表达与肾脏纤维化程度相关。     

门静脉高压大鼠局部肾素血管紧张素系统活性的改变

本研究应用逆转录聚合酶链反应(RT-PCR)方法,检测门静脉高压(PH)大鼠肝、肾脏局部肾素、血管紧张素原mRNA的表达,以探讨其在门静脉高压内脏血流动力学紊乱中的作用。1.材料与方法:(1)动物模型的制作:选取30只健康SD大鼠随机数字法分为PH组18只和假手术(SO)组12只。采用门静脉部分缩窄法建立门静脉高压动物模型。SO组只游离而不结扎门静脉。术后,PH组死亡4只,SO组死亡1只,所余25只用于本实验研究。(2)取材和检测:3周后颈椎脱臼法处死两组动物,剖腹取肾脏及肝脏组织,立即置于-80℃液氮保存备用。应用RT-PCR技术检测大鼠肝、肾脏局…     

肾素血管紧张素系统与造血调控研究进展

肾素-血管紧张素系统（RAS）的主要生物学作用体现在对血压和水、电解质的调控上.近年来的研究表明,RAS参与造血调控,其主要活性物质血管紧张素Ⅱ（AngⅡ）促进红系造血,而其受体拮抗剂（ARB）和血管紧张素转换酶抑制剂（ACEI）抑制红系造血.     

阻断肾素血管紧张素系统对慢性肾脏疾病的治疗作用

众所周知，我们正面临着越来越多的进展性肾脏病患者，而血管紧张素Ⅱ（AngⅡ）在肾脏疾病进展中起着重要作用。因此，阻断肾素血管紧张素系统（RAS）是阻止慢性肾脏病进展的关键。几个大型临床试验已经清楚地显示，血管紧张素转换酶抑制剂（ACEI）治疗能减慢肾脏疾病的进展，包括糖尿病肾病，这种效果部分不依赖于血压的控制。近来，用AngⅡ1型受体（AT1）拮抗剂（ARB）治疗2型糖尿病，对肾功能同样具有保护作用。     

肾素-血管紧张素系统的新概念（上）

近年来，在肾素-血管紧张素系统（R峪）方面的研究有了很大的进展，如发现血管紧张素酶-2（A（=E2）和糜蛋白酶作用的重要性，确认了血管紧张素17（Ang1-7）和血管紧张素Ⅳ（AngⅣ）的活性作用，这些活性物质与血管紧张素Ⅱ（AngⅡ）具相辅相成和相生相克作用，因此我们需更新对RAS的认识。     

The relationship between kidney function and body mass index before and after bariatric surgery in patients with chronic kidney disease

BackgroundImprovements in kidney function post–bariatric surgery may be related to weight loss–independent effects.ObjectivesTo characterize the dynamic relationship between body mass index (BMI) and estimated glomerular filtration rate (eGFR) before and after bariatric surgery in patients with chronic kidney disease (CKD).SettingKaiser Permanente Southern California (KPSC) health system.MethodsWe conducted an observational, retrospective cohort study of patients with CKD stage 3 or higher who received bariatric surgery at the KPSC health system between 2007–2015. Bariatric surgery procedures included primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) procedures. Outcomes consisted of mean trajectory estimates and correlations of BMI and eGFR taken between 2 years before and 3 years after surgery. Multivariate functional mixed models were used to estimate how BMI and eGFR trajectories evolved jointly.ResultsA total of 619 RYGB and 474 SG patients were included in the final analytic sample. The measurements were available before surgery for a median time of 1.9 years for SG and 1.8 years for RYGB patients. Median follow-up times after surgery were 2.8 years for both SG and RYGB patients. The mean age at the time of surgery was 58 years; 77% of patients were women; 56% of patients were non-Hispanic White; the mean BMI was 44 kg/m²; 60% of patients had diabetes mellitus; and 84% of patients had hypertension. Compared to the presurgery eGFR declines, the postsurgery declines in eGFR were 57% slower (95% credible interval [CrI], 33%–81%) for RYGB patients and 55% slower (95% CrI, 25%–75%) for SG patients. The mean correlation between BMI and eGFR was negligible at all time points.ConclusionThough bariatric surgery slowed declines in eGFR up to 3 years after surgery, changes in eGFR tracked poorly with changes in BMI. This study provides evidence that the kidney-related benefits of bariatric surgery may be at least partly independent of weight loss. Confirming this hypothesis could lead to mechanistic insights and new treatment options for CKD.     

双重阻断肾素-血管紧张素系统对慢性肾脏疾病血压、蛋白尿和肾功能的影响

目的 观察长程应用ACEI联合ARB治疗慢性肾脏疾病的疗效和安全性。 方法 60例慢性肾脏疾病患者随机分为3组：ACEI组、ARB组和联合组，ACEI组接受贝那普利治疗，ARB组接受缬沙坦治疗，联合组接受贝那普利联合缬沙坦治疗。观察治疗后1、3、6、9和12个月的相关临床指标变化，并进行评价。 结果 3 组患者经过12个月治疗后，24 h尿蛋白从(1.08±0.68) g降至(0.27±0.29) g，P < 0.05；收缩压从(129±24) mm Hg降至(116±18) mm Hg(P < 0.05)；肾小球滤过率从(67.5±30.2)ml/min升至(69.3±34.6)ml/min(P > 0.05)；血钾变化不大(P > 0.05)；不良反应轻微。3 组相比，联合组有最强的减少尿蛋白和降低舒张压作用(P < 0.05)，而在肾功能改善、血钾变化及不良反应方面，3 组间差异无统计学意义(P > 0.05)。结论 长期联合治疗双重阻断RAS系统有更强地降低蛋白尿和舒张压作用，而不良反应轻微。     

Cystatin C相关方程在计算慢性肾脏病肾小球滤过率的对照研究

目的 评价血清半胱氨酸蛋白酶抑制剂C（Cystatin C,CysC）相关方程在不同病因引起慢性肾脏病（CKD）患者的肾小球滤过率（GFR）计算中的临床应用价值。方法选择CKD患者255例,运用MDRD方程（mGFR）、MDRD简化方程（rnGFR）、Hoek方程（hGFR）、2006年中华医学会肾脏病学分会推荐的方程（c-cGFR1,c-cGFR2）计算GFR,与^99m-二乙撑三胺五乙酸（^99m TcDT-PA）肾动态显像测得的。肾小球滤过率（sGFR）进行比较。结果在分期比较中,各方程估算的GFR和sGFR相关性一般,CysC相关方程能更敏感反应GFR;在不同病因分组中,各方程估算的GFR和sGFR均明显相关,特别是c-cGFR2。结论在CysC相关方程中,以2006中华公式2计算的c-cG-FR2与sGFR相关性及一致性最好,并且在糖尿病肾脏病组中,各方程相关系数优于其他组别,有必要进一步大规模临床研究证明其应用价值。     

Risk factors and urinary biomarkers of non-albuminuric and albuminuric chronic kidney disease in patients with type 2 diabetes

BACKGROUND A number of recent studies indicate a transformation in the natural course of chronic kidney disease(CKD) in type 2 diabetes(T2 D) patients: an increasing prevalence of declined renal function without proceeding to the accompanying elevation of albuminuria. It has been suggested that albuminuric and nonalbuminuric CKD patterns could be different in their phenotypes and pathogenic mechanisms.AIM To identify the risk factors and biomarkers of albuminuric and non-albuminuric patterns of CKD in patients with T2 D.METHODS Three hundred sixty patients with T2 D duration ≥ 10 years were included in this observational cross-sectional study. The associations of a panel of demographic and clinical characteristics, complications, comorbidities, and metabolic and hematology parameters with albuminuric and non-albuminuric CKD patterns were analyzed. The urinary excretion of nephrin and podocin, two podocytespecific markers, and WAP-four-disulfide core domain protein 2(WFDC-2), a marker of tubulointerstitial fibrosis, was determined by ELISA in comparison with healthy controls.RESULTS Non-albuminuric CKD was associated with age ≥ 65 years(P = 0.0001), female sex(P = 0.04), diabetes duration ≥ 15 years(P = 0.0009), and the use of diuretics(P= 0.0005). Male sex(P = 0.01), smoking(P = 0.01), waist-to-hip ratio 1.0(P = 0.01)and hemoglobin A1 c(Hb A1 c) 8.0%(P = 0.005) were risk factors for elevated albuminuria not accompanied by a decrease in estimated glomerular filtration rate(e GFR). Duration of diabetes ≥ 15 years and the use of calcium channel blockers were risk factors for albuminuria with decreased e GFR(both P = 0.01).In multivariate logistic regression analysis, age, Hb A1 c, female sex and diuretics were significant predictors for reduced e GFR, while waist-to-hip ratio, Hb A1 c and male sex were associated with elevated urinary albumin-to-creatinine ratio(UACR). Excretion of nephrin and podocin was increased in patients with albuminuria, regardless of decline in renal function(P 0.001), correlating positively with UACR. The urinary excretion of WFDC-2 was markedly higher in men than in women(P 0.000001). Men with T2 D demonstrated increased WFDC-2 levels independently of the CKD pattern(all P 0.05). In T2 D women,WFDC-2 excretion was increased in those with reduced renal function(P ≤ 0.01),correlating negatively with e GFR.CONCLUSION The data provide further evidence that albuminuric and non-albuminuric CKD phenotypes correspond to different pathways of diabetic kidney disease progression.     

MDRD方程在我国慢性肾脏病患者中的改良和评估

目的开发适合我国慢性肾脏病(CKD)患者的肾小球滤过率(GFR)评估方程。方法收集国内不同地域、肾功能不同分期的CKD患者684例的有关资料。随机选取454例为开发组,230例为验证组。以双血浆法~(99m)Tc-DTPA血浆清除率为GFR参考值。(1)在简化MDRD方程中添加种族系数；(2)多元逐步回归线法开发新的GFR评估方程；(3)将上述两种改良的方程与改良前简化MDRD方程进行偏离度、精确度、准确性比较。结果684例患者中,男352例,女332例,平均年龄(49．9±15．8)岁。上述两种改良的简化MDRD方程在肾功能不同分期内偏离度分别为543．0、677．2和2175．0任意单位；精确度分别为57．5、56．5和60．7 ml·min~(-1)·(1．73 m~2)~(-1)；准确性均优于改良前简化MDRD方程,差异有统计学意义(30%的准确性由66．1%提高至77．8%和79．6%,P＜0．05)。结论基于我国CKD人群特点,改良的简化MDRD方程与改良前方程相比,表现了显著的优势,可以替代改良前简化MDRD方程,应用于我国CKD患者的GFR评估。     

Comparison of different equations for estimated glomerular filtration rate in patients with chronic kidney disease

Objective To compare different equations for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD). Methods Hospitalized patients with CKD from the nephrology department of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) were recruited between December 2014 and May 2015. The calculations of eGFR and 24 h creatinine clearance rate (Ccr) were accomplished in three days after admission. The eGFRs were calculated separately using the 24 h creatinine clearance rate adjusted by the standard body surface area (Ccr_BSA), Cockcroft-Gault equation adjusted by the standard body surface area (eCcr_BSA), CKD-EPI creatinine equation (EPI_Cr), CKD-EPI cystatin C equation (EPI_CysC), CKD-EPI creatinine-cystatin C equation (EPI_Cr_CysC), simplified MDRD (MDRD) and China MDRD equations. The EPI_Cr_CysC equation was used as the standard and the precision and accuracy of the other six equations were compared and analyzed. Results A total of 403 CKD participants were enrolled in the study, with 228 male patients and a mean age of (54.9±18.4) years. The main primary diseases were chronic glomerulonephritis (43.7%) and diabetic nephropathy (13.2%). The median concentration of serum creatinine and cystatin C were 117.5 (69.7, 242.4) μmol/L and 1.80 (1.13, 3.31) mg/L, respectively. The median values of Ccr_BSA, eCcr_BSA, MDRD, China MDRD, EPI_Cr, EPI_CysC and EPI_Cr_CysC equations were 50.8 (21.1, 96.2), 51.9 (23.3, 93.2), 53.6 (23.0, 97.4), 52.2 (22.4, 94.1), 53.2 (22.1, 97.3), 35.1 (15.4, 67.0) and 49.1 (22.8, 82.3) ml?min-1?(1.73 m2)-1, respectively. There was well agreement among MDRD, China MDRD and EPI_Cr equations, while there were large differences between equations derived from CysC (EPI_Cr_CysC and EPI_CysC) and equations derived only from creatinine (EPI_Cr, MDRD, China MDRD, eCcr_BSA, Ccr_BSA equations). Compared with EPI_Cr_CysC equation (the reference equation), EPI_Cr equation showed the highest accuracy [percentage of other eGFR equation calculations that were ＞30% of the reference equation calculations (1-P30), 30.8%] while Ccr_BSA equation showed the lowest (1-P30, 42.4%). EPI_CysC equation showed the highest precision [inter-quartile range (IQR) of the difference, 11.7 ml?min-1?(1.73 m2)-1] while Ccr_BSA equation showed the lowest [IQR of the difference, 22.8 ml?min-1?(1.73 m2)-1]. Conclusions The agreement among equations derived only from creatinine is better; while it exhibits some differences between equations with cystatin C and equations derived only from creatinine. The accuracy of EPI_Cr equation is second only to EPI_Cr_CysC equation and it is currently the most suitable eGFR equation for clinical popularization of renal glomerular function assessment.     

CKD—EPI方程在慢性肾脏病患者中的适用性

目的探讨慢性。肾脏病流行病学合作研究（CKD-EPI）方程对评估中国人肾小球滤过率（GFR）的适用性。方法选择CKD患者42例,对其以CKD-EPI方程估算GFR（eGFR）与BSA标准化的99mTc-DTPA肾动态显像法测定的GFR（sGFR）进行比较。结果eGFR与sGFR呈正相关（r=0．868,P〈0．01）;eGFR的15％、30％及50％符合率分别是23．8％、40．5％和64．3％,eGFR与sGFR平均偏差5．46ml／min。结论CKD-EPI方程可广泛应用于评估CKD患者GFR,但仍然存在偏差,需进行大规模试验并根据CKD不同分期进行适用性研究。     

肾移植术后一年时的肾小球滤过率与移植肾长期功能的相关性研究

目的 探讨肾移植受者术后1年时的肾小球滤过率(GFR)与移植肾长期功能的相关性. 方法 回顾性分析1994年11月至2004年10月间334例肾移植受者的临床资料.根据术后1年时的GFR不同,将受者分成肾功能正常组(≥1.083 ml/s; 267例)和肾功能异常组(GFR＜1.083 ml/s;67例))GFR采用Coekeroft-Gault(C-G)公式进行计算.采用Kaplan-Meier方法比较两组受者术后5年时移植肾的长期存活率;分析术后1年与术后5年时GFR的相关性. 结果 肾移植术后移植肾存活率呈现逐年下降趋势,术后1年时的GFR与移植肾存活时间成正比,术后同一时间点(5年、10年),肾功能正常组(不包括或包括肾功能正常的死亡者)移植.肾的长期存活率均高于肾功能异常组,两组比较,差异有统计学意义(P＜0.05).与术后1年时GFR比较,术后5年时的GFR变化幅度为(0.080±0.248)ml/s,其下降程度与术后1年时的GFR呈现明显正相关性. 结论 术后1年时的GFR水平影响移植肾的长期功能,术后1年时的GFR越高,术后5年的GFR也越高.