Mild hyperuricemia and subclinical renal damage in untreated primary hypertension

BACKGROUND: Subclinical renal damage and hyperuricemia are not uncommon in patients with primary hypertension. Whether mild hyperuricemia reflects a subclinical impairment of renal function or contributes to its development is currently debated. We investigated the relationship between serum uric-acid levels and the occurrence of early signs of kidney damage. METHODS: Four hundred eighteen patients with primary hypertension were studied. Albuminuria was measured as the albumin-to-creatinine ratio, and creatinine clearance was estimated by the formula of Cockcroft and Gault. Interlobar resistive index and renal abnormalities, ie, the renal volume-to-resistive index ratio, were evaluated by renal Doppler and ultrasound. RESULTS: Uric acid was directly related to resistive index (P = .007) in women and to albuminuria (P = .04) in men, and was inversely related to the renal volume-to-resistive index ratio in both men (P = .005) and women (P = .02). Patients with uric-acid levels above the median showed a higher prevalence of microalbuminuria (14% v 7%, P = .012) and of renal abnormalities (41% v 33%, P = .007). Moreover, when creatinine clearance was taken as a covariate, patients with increased uric-acid levels showed higher albuminuria and resistive indices, and a lower renal volume-to-resistive index ratio. Even after adjustment for several risk factors, each standard deviation increase in serum uric acid entailed a 69% higher risk of microalbuminuria, and a 39% greater risk of ultrasound detectable renal abnormalities. CONCLUSIONS: Mild hyperuricemia is associated with early signs of renal damage, ie, microalbuminuria and ultrasound-detectable abnormalities, regardless of the glomerular filtration rate in primary hypertension.     

Urinary albumin excretion in a population based sample of 1011 middle aged non-diabetic subjects

Jensen JS, Feldt-Rasmussen B, Borch-Johnsen K, Jensen G and The Copenhagen City Heart Study Group. Urinary albumin excretion in a population based sample of 1011 middle-aged non-diabetic subjects. Scand J Clin Lab Invest 1993; 53: 867-872

Increased urinary albumin excretion rate (UAER) especially in the range of 20-200 μg min^?1, termed microalbuminuria, has been proposed as a risk marker and predictor for cardiovascular disease in non-diabetic subjects. Thus it would be of importance to describe the distribution of UAER in the non-diabetic population. Among 1011 30-70-year-old subjects without diabetes mellitus or urinary tract infection, who were invited to participate in a population based epidemiological study, the albumin concentration was measured in an overnight urine sample. The measurement was performed by an ELISA method. The UAER was calculated in units of μgmin^?1 as urinary albumin concentration × urine volume/urine collection time. The distribution of UAER was positively skewed with a median value of 2.3μgmin^?1 and a 5-95 inter-percentile range of 0-11.0μgmin^?1. The UAER held constant with age, but males had higher UAER than females, 2.6 (0-13.5)μgmin^?1 vs 2.2 (0-8.3)μgmin^?1; p < 0.005. The prevalence of microalbuminuria, defined as an UAER in the range of 15-150μgmin^?1 in an overnight urine sample, was 3% (95% C.I. interval: 1.9-4.0). These findings suggest, that the level of UAER which might notify increased cardiovascular risk, is lower than in patients with diabetes mellitus, if it is considered to be of any clinical relevance.     

Differential regulation of mesothelial cell fibrinolysis by transforming growth factor beta 1

Management of hypertension and diabetes mellitus in primary health care requires occasional assessment of kidney function. Monitoring the urinary albumin excretion every 24?h is often used as a diagnostic gold standard but measurement of U‐Albumin concentrations in morning urine either alone or together with U‐Creatinine is a well‐established surrogate measure. We compared the ratio U‐Albumin/U‐Creatinine and U‐Albumin concentrations measured by commonly used POC (Point of care) instruments with those obtained in a central laboratory and estimated the uncertainty of the results after establishing an uncertainty budget. It is concluded that the presentation of ratios or concentrations on an ordinal scale is less satisfactory than reporting U‐Albumin concentration on a ratio scale. Moreover the latter will have the advantage of allowing the physician to adjust the diagnostic sensitivity and specificity to local needs. The present report is a methodological study and does not consider the diagnostic performance of the studied properties per se.     

An aid to the early detection and management of diabetic nephropathy: assessment of a new point of care microalbuminuria system in the diabetic clinic.

AIMS: To compare the performance of the DCA2000 microalbuminuria system for albumin and creatinine concentrations and the albumin:creatinine ratio (ACR) with laboratory measurements in the hospital diabetes clinic and to assess the ease of use and applicability by standard clinic personnel. METHODS: Urine albumin and creatinine concentration and ACR were measured in 154 diabetic patient samples and in 77 normal subjects. Both albumin assays are based on immunoturbidimetry. The DCA2000 system utilizes reagent cartridges processed automatically. RESULTS: Control material within-run precision (coefficient of variation (CV)) for albumin and creatinine ranged up to 7.1% and 3.3% respectively. Between-run CVs ranged from 2.1% to 4.3%. Method comparisons yielded correlation coefficients > 0.99 for albumin, creatinine and ACR, only a small negative bias of 3.2 mg/l for albumin and 0.10 mg/mmol for ACR, no concentration-related bias for ACR and no between-method difference for either albumin (P = 0.195) or ACR (P = 0.341). At a laboratory albumin concentration cut-off of 20 mg/l the sensitivity, specificity, negative and positive predictive values were 92.4% 100% 92.7% and 100%. Normal reference range mean albumin, creatinine and ACR values for the DCA2000 and the laboratory were 7.7 mg/l vs. 9.0 mg/l 13.0 mmol/l vs. 12.6 mmol/l and 0.66 mg/mmol vs. 0.81 mg/mmol respectively. Clinic personnel found that the DCA2000 system was easy to use suited the clinic environment and generated confidence in the results. CONCLUSIONS: This point of care system safely substitutes laboratory-based measurements. Ease of use and low cost make it suitable for screening and monitoring diabetes treatment. It facilitates the use of random urines, and may obviate the need for timed samples. This approach has a clear place in the battle to reduce the diabetic vascular disease burden.     

Predictors of the development of microalbuminuria in patients with Type 1 diabetes mellitus: a seven-year prospective study

Aims To determine risk factors for the development of persistent microalbuminuria (albumin excretion rate (AER) ≥ 30 μg/min) in Type 1 diabetes mellitus. Methods One hundred and forty-eight initially normotensive Type 1 diabetic patients with normal albumin excretion (< 30 μg/min) were followed prospectively in hospital diabetes outpatient clinics for a median of 7 years. Main outcome measures were: progression to persistent microalbuminuria (albumin excretion rate ≥ 30 μg/min on at least two consecutive occasions); rate of change of albumin excretion rate; development of arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg or commencement of antihypertensive therapy). Results In a median follow-up period of 7 years (range 6 months to 8 years), 14 patients progressed to persistent microalbuminuria, a cumulative incidence of 11% (95% confidence interval 6.36–16.94). AER remained persistently < 30 μg/min in 109 subjects and 25 developed intermittent microalbuminuria. In those who developed persistent microalbuminuria, baseline AER (16.2 (13.9–19.1) vs. 5.2 (3.8–9.2) μg/min, P < 0.01), blood pressure (136 (123–148)/80 (74–85) vs. 121 (118–124)/72 (70–73) mmHg, P < 0.05), and HbA₁ (10.2 (9.1–11.4) vs. 9.0 (8.7–9.4)%, P < 0.05) were higher than in those who continued to have persistent normoalbuminuria, retinopathy was more severe and height (1.64 (1.57–1.71) vs. 1.70 (1.69–1.72) m, P < 0.05) less. In multivariate analysis, baseline AER was the strongest predictor of the development of persistent microalbuminuria (P < 0.0001), followed by mean arterial pressure (P = 0.02) and HbA₁ (P = 0.05). Conclusions The level of AER, raised blood pressure and poor glycaemic control are the most important predictors of the development of microalbuminuria in Type 1 diabetes.     

Pulse pressure and subclinical cardiovascular damage in primary hypertension.

BACKGROUND: High pulse pressure (PP) values have recently been implicated in the development and progression of large vessel atherosclerosis, small vessel disease, and in the occurrence of cardiovascular events. The aim of the present study is to investigate the relationship between PP and subclinical cardiovascular damage in a cohort of unselected middle-aged patients (204 male, 129 female) with untreated primary hypertension. METHODS: PP was calculated as the difference between systolic (SBP) and diastolic blood pressure (DBP). Left ventricular mass index (LVMI) was assessed by M-B mode echocardiography (LVH=LVMI>51 g/m(2.7)), and carotid intima-media thickness (IMT) by high-resolution US scan. Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. RESULTS: PP was positively correlated to gender (P<0.05), duration of disease (P<0.001), age (P<0.0001), LDL cholesterol (P=0.007), and to early signs of target organ damage (TOD), namely LVMI (P<0.0001), IMT (P<0.0001), and ACR (P=0.036). Patients in the upper quartile of PP showed higher LVMI (P<0.001), thicker carotid walls (P<0.001), as well as higher ACR (P<0.04). Multiple linear regression analysis showed that PP and ACR independently influence LVMI (F=26.476, r(2)=0.29, P<0.0001) and IMT (F=17.813, r(2)=0.26, P<0.0001). Patients with LVH, increased carotid IMT and microalbuminuria showed higher PP values as compared with those with lesser degrees of target organ involvement (F=4.97, P<0.003 inter-group comparison). Moreover, the risk of having the simultaneous occurrence of various signs of TOD increases significantly with each SD increase in PP or SBP, but is not influenced by DBP. CONCLUSIONS: PP is an independent marker of preclinical cardiovascular damage in relatively young patients with primary hypertension and, therefore, can be useful for identifying those at higher risk of cardiovascular events.     

ACEI影响血压正常的糖尿病人尿白蛋白分泌的荟萃分析

目的对血管紧张素转化酶抑制剂(ACEI)是否能有效抑制血压正常的糖尿病人的尿白蛋白分泌进行系统评价.方法查阅自1980年1月至2004年3月期间发表的有关ACEI对血压正常的糖尿病人尿蛋白影响效应的随机对照临床试验研究文献.选择的检索数据库有:Medline(1980-2003),Embase数据库(Embase database)(1980-2000),Cochrane图书馆(Co-chrane Library,CL)(1980-2004),中国生物医学文献数据库(CBMdisc)(1980-2002),国际药学文献(IPA)(1980-2002).最终入选7项随机对照试验.采用Revman 4.2软件对试验结果进行合并分析.结果7项试验治疗末期AER值与基线值差值的合并治疗效应为-56.31μg·min-1[-81.96,-30.66](P＜0.0001),具显著的统计学意义.根据亚组分析结果,治疗1-5年期AER值与基线值差值的合并治疗效应分别为-11.97μg·min-1[-22.04,-1.89](P=0.02),-28.01μg·min-1[-34.50,-21.52](P＜0.00001),-43.24μg·min-1[-57.15,-29.32](P＜0.00001),-61.25μg·min-1[-77.77,-45.54](P＜0.00001),-98.41μg·min-1[-162.02,-34.79](P=0.002),均有显著统计学意义.治疗末期由微量蛋白尿发展为临床蛋白尿的数据合并效应量PetoOR=0.27[0.18,0.40](95%CI),P＜0.00001,具有显著的统计学意义.2年期,5年期亚组合并效应量Peto OR=0.30[0.18,0.51](P＜0.00001),PetoOR=0.25[0.13,0.50](P＜0.0001),均具有显著统计学意义.各分析结果发表偏倚影响均较小.结论对血压正常的早期糖尿病患者,ACEI有效降低了尿白蛋白的排泄率,减缓了糖尿病人由微量蛋白尿发展为临床蛋白尿的进程.     

24-h blood pressure and autonomic function is related to albumin excretion within the normoalbuminuric range in IDDM patients

Summary Significant changes in both blood pressure, autonomic function and kidney ultrastructure are observed in insulin-dependent diabetic (IDDM) patients with microalbuminuria. Intervention strategies are evaluated at even earlier stages of disease. Identification of patients at risk of developing microalbuminuria must be based on a thorough knowledge of the relations between key pathophysiological parameters in patients with normoalbuminuria. The aim of the present study was to characterize the interactions of urinary albumin excretion (UAE), 24-h ambulatory blood pressure (AMBP), and sympathovagal balance in a large group of normoalbuminuric IDDM patients. In 117 normoalbuminuric (UAE < 20 μg/min) patients we performed 24-h AMBP (Spacelabs 90 207), with assessment of diurnal blood pressure and heart rate (HR) variation, and short-term (three times 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (HR variation to deep breathing, postural HR and blood pressure response). Patients with UAE above the median (4.2 μg/min) had significantly higher 24-h systolic and diastolic AMBP (125 ± 10.1/76 ± 7.2 mmHg) compared to the low normoalbuminuric group (120 ± 8.4/74 ± 5.1 mmHg), p < 0.01 and 0.02, respectively. Patients with UAE above the median had significantly reduced short-term RR interval variability including both the high frequency component (5.47 ± 1.36 vs 6.10 ± 1.43 ln ms²), and low frequency component (5.48 ± 1.18 ln ms² compared to 5.80 ± 1.41 ln ms²), p < 0.02 and p = 0.04 (ANOVA). In addition, patients with high-normal UAE had reduced mean RR level (faster heart rates) 916 ± 108 compared to 963 ± 140 ms, p < 0.04. These differences were not explained by age, duration of diabetes, gender, level of physical activity, or cigarette smoking. HbA_{1 c} was significantly higher (8.6 ± 1.2 vs 8.2 ± 1.0 %, p = 0.03) in the group with high normal UAE. Comparing normoalbuminuric IDDM patients with UAE above and below the median value, we found significantly higher AMBP in combination with significant differences in sympathovagal balance and significantly poorer glycaemic control in the group with high-normal albumin excretion. Our data demonstrate interactions between albumin excretion, blood pressure, autonomic function, and glycaemic status, already present in the normoalbuminuric range and may describe a syndrome indicative of later complications. [Diabetologia (1997) 40: 718–725] Received: 9 January 1997 and in revised form: 12 March 1997     

不同剂量氯沙坦对高血压病并发Ⅱ型糖尿病患者微量白蛋白尿及血管内皮功能的影响

目的探讨不同剂量氯沙坦对高血压病并发Ⅱ型糖尿病患者微量白蛋白尿及血管内皮功能的影响。方法将31例伴有持续微量白蛋白尿的高血压病并发Ⅱ型糖尿病患者随机分为2组,分别接受氯沙坦50mg/d（A组,16例）及100mg/d（B组,15例）口服治疗16周,检测并比较两组患者治疗前后尿白蛋白排泄率（UAER）、肱动脉血流介导的血管舒张反应（FMD）。结果A、B两组患者经氯沙坦治疗16周后平均UAER水平分别由（114±31）μg/min、（108±30）μg/min降至（92±26）μg/min、（74±28）μg/min（均P<0.01）,B组降低程度更为显著（P<0.05）;A、B两组患者治疗后平均FMD内径变化率分别由治疗前（6.5±1.9）%、（6.8±1.0）%增至（7.0±1.2）%、（7.2±1.1）%（均P<0.01）,B组的增加程度更为显著（P<0.05）。UAER与FMD内径变化率呈负向线性关系（r=-0.78,P<0.05）。结论与每日使用50mg氯沙坦相比,每日使用100mg氯沙坦可以更为显著地降低这类患者尿微量白蛋白的排泄,更为有效地改善其血管内皮功能,并且具有良好的安全性及耐受性。     

人体测量学肥胖判定指标与微量白蛋白尿的相关性

目的:探讨各项人体测量学肥胖判定指标与微量白蛋白尿(MAU)的相关性。方法:采取分层的整群随机抽样方法,从糖尿病流行病学调查数据库中抽取1 170例,清晨留取随机测定尿微量白蛋白和尿肌酐,根据尿微量白蛋白/尿肌酐比值(UACR)水平分为:正常白蛋白尿(NAU)组(男398例,女409例)和MAU组(男175例,女188例)。收集一般临床资料和测定生化指标,统计学处理采用SPSS 16.0软件。结果:与NAU组相比,MAU组年龄、空腹血糖(FBG)、舒张压(DBP)、收缩压(SBP)、血清尿酸(SUA)、腰围(WC)、腰身比(WHtR)、腰臀比(WHR)、高血糖(HG)、原发性高血压、血脂异常及肥胖,尤其腹型肥胖患病率均高于前者,差异有统计学意义;多元线性回归分析,年龄、DBP、FBG、WHtR、WC、WHR与UACR相关。调整年龄、性别、FBG及DBP等因素后,对MAU影响大小依次WHtRWCWHR;采用受试者工作特征曲线(ROC)分析男性人群WHtR、WC、WHR等预测MAU的曲线下面积依次为0.68(95%CI:0.67-0.70)、0.64(95%CI:0.62-0.65)、0.57(95%CI:0.55-0.59),预测切点0.52、91.8、0.90cm。在女性人群中,WHtR、WC、WHR等预测MAU的曲线下面积依次为0.71(95%CI:0.70-0.72)、0.69(95%CI:0.68-0.70)和0.64(95%CI:0.62~0.65),预测切点0.52、82.5、0.84 cm。结论:人体测量学腹型肥胖指标与微量白蛋白尿密切相关,可作为预测、评估人群患病风险的简易指标;在人体测量学腹型肥胖指标中,WHtR是预测本地区人群微量白蛋白尿等风险的最好指标,最佳切割点为0.52。