Increased arterial stiffness in young adults with end-stage renal disease since childhood

Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa(-1). 10(-3); 95% CI, -9.1 to -0.8; P < 0.001), an increased stiffness parameter beta (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P = 0.02), an increased elastic incremental modulus E(inc) (0.35 versus 0.27 kPa. 10(3); 95% CI, 0.02 to 0.12; P < 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in beta and E(inc). Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E(inc) and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.     

Relationship between albuminuria, low eGFR, and carotid atherosclerosis in Japanese women

In this cross-sectional study, we have investigated whether chronic kidney disease components were associated with carotid plaque and carotid intima-media thickening in women. Between April 2005 and May 2006, 830 women underwent general health screening including carotid ultrasonography and urinary albumin excretion, and were enrolled in the study. Of these individuals examined, 83 (10%) had albuminuria, 203 (24%) had low estimated GFR (eGFR), and 24 (3%) had both albuminuria and low eGFR. Univariate analysis showed that albuminuria, but not low eGFR, was associated with carotid plaque, and that both albuminuria and low eGFR were positively associated with carotid intima-media thickening. Age-adjusted logistic regression analysis showed that albuminuria was positively associated with carotid plaque with an odds ratio of 2.48 (95% CI 1.49-4.11, p < 0.001). On the other hand, association between albuminuria and carotid intima-media thickening was not statistically significant after age adjustment. Positive association between albuminuria and carotid plaque was present when either hypertension or high fasting glucose was absent. In conclusion, in Japanese women who underwent general health screening, albuminuria, but not low eGFR, was positively associated with carotid plaque.     

Urinary albumin excretion associated with arterial wall stiffness rather than thickness in type 2 diabetic patients

BACKGROUND: A close relationship has been reported between microalbuminuria and atherosclerosis in patients with diabetes mellitus. The aim of this study was to determine which of the 2 aspects of atherosclerosis, arterial thickening or stiffness, has more effect on levels of microalbuminuria in type 2 diabetic patients. METHODS: Twenty-four-hour urine samples of 167 Japanese type 2 diabetic patients (aged 58 +/- 12 years) without overt proteinuria were collected for quantitative analysis of urinary albumin excretion (UAE). Arterial stiffness was evaluated by measuring aortic pulse-wave velocity (PWV), and arterial thickness was measured by the intima-media thickness (IMT) of the carotid artery. RESULTS: The aortic PWV and carotid IMT were both significantly positively correlated with logarithmically transformed UAE (r=0.269, p<0.001; and r=0.188, p<0.05, respectively). Although there was a significant positive correlation between aortic PWV and carotid IMT (r=0.263, p<0.001), multiple regression analyses demonstrated that aortic PWV, but not carotid IMT, was a significant factor associated with log UAE, independent of other confounding factors (R2=0.246, p<0.0001). CONCLUSIONS: These results suggest that increased arterial stiffness, but not arterial thickness, is significantly associated with the increase in albuminuria, and that decreased arterial distensibility due to increased stiffness caused by atherosclerosis may be related to the progression of diabetic nephropathy in type 2 diabetic patients.     

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.     

Arterial remodeling associates with CKD progression

In CKD, large arteries remodel and become increasingly stiff. The greater pulsatile pressure reaching the glomerulus as a result of increased aortic stiffness could induce renal damage, suggesting that the stiffening and remodeling of large arteries could affect the progression of CKD. We measured carotid-femoral pulse wave velocity, aortic pressure and carotid remodeling and stiffness parameters in 180 patients with CKD (mean measured GFR, 32 ml/min per 1.73 m(2)) and followed them prospectively for a mean of 3.1 years. During follow-up, carotid stiffness significantly increased (+0.28 ± 0.05 m/s; P<0.0001) but aortic stiffness did not. Carotid intima-media thickness decreased significantly during follow-up and the internal diameter of the carotid increased, producing increased circumferential wall stress (+2.08 ± 0.43 kPa/yr; P<0.0001). In a linear mixed model, circumferential wall stress significantly associated with faster GFR decline after adjustment for risk factors of cardiovascular disease and progression of CKD. In a multivariable Cox model, carotid circumferential wall stress and pulse pressure independently associated with higher risk for ESRD. None of the arterial stiffness parameters associated with progression of CKD. In conclusion, maladaptive remodeling of the carotid artery and increased pulse pressure independently associate with faster decline of renal function and progression to ESRD.     

Albuminuria and racial disparities in the risk for ESRD

The causes of the increased risk for ESRD among African Americans are not completely understood. Here, we examined whether higher levels of urinary albumin excretion among African Americans contributes to this disparity. We analyzed data from 27,911 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) measured at baseline. We identified incident cases of ESRD through linkage with the United States Renal Data System. At baseline, African Americans were less likely to have an eGFR <60 ml/min per 1.73 m(2) but more likely to have an ACR ≥ 30 mg/g. The incidence rates of ESRD among African Americans and whites were 204 and 58.6 cases per 100,000 person-years, respectively. After adjustment for age and gender, African Americans had a fourfold greater risk for developing ESRD (HR 4.0; 95% CI 2.8 to 5.9) compared with whites. Additional adjustment for either eGFR or ACR reduced the risk associated with African-American race to 2.3-fold (95% CI 1.5 to 3.3) or 1.8-fold (95% CI 1.2 to 2.7), respectively. Adjustment for both ACR and eGFR reduced the race-associated risk to 1.6-fold (95% CI 1.1 to 2.4). Finally, in a model that further adjusted for both eGFR and ACR, hypertension, diabetes, family income, and educational status, African-American race associated with a nonsignificant 1.4-fold (95% CI 0.9 to 2.3) higher risk for ESRD. In conclusion, the increased prevalence of albuminuria may be an important contributor to the higher risk for ESRD experienced by African Americans.     

Studies on effects of calcineurin inhibitor withdrawal on arterial distensibility and endothelial function in renal transplant recipients

Whether withdrawal of calcineurin inhibitors has a beneficial effect on disturbed endothelial function and large artery distensibility in renal transplant recipients is not clear. We studied the effects of cyclosporine A (CsA) withdrawal on arterial compliance and endothelium-dependent flow-mediated vasodilatation (FMD) in a prospective, randomized trial; 24 renal transplant recipients receiving mycophenolate mofetil were randomized to withdrawal (n=12) or continuation of CsA (n=12). At baseline and after 6 months, carotid and brachial artery distensibility coefficients and brachial FMD were measured. Brachial distensibility coefficients increased in both groups (withdrawal: 11.1+/-1-14.9+/-2 10(-3)/kPa, continuation: 10.7+/-1-15.2+/-3 10(-3)/kPa, P<0.05, respectively). However, there was no significant effect of treatment on carotid artery distensibility coefficients, FMD, or graft function. Withdrawal of CsA failed to improve carotid artery distensibility or brachial FMD in patients after renal transplantation. Our data indicate that CsA treatment does not contribute significantly to endothelial dysfunction observed in renal transplant recipients.     

Association of Serum Pentosidine With Arterial Stiffness in Hemodialysis Patients

Pentosidine is an advanced glycation end product (AGE). The present study was undertaken to investigate the association of serum pentosidine with carotid distensibility as a measure of arterial stiffness in hemodialysis patients. One hundred and three patients on maintenance hemodialysis were recruited. The distensibility coefficient of the common carotid artery was evaluated by an ultrasonic phase‐locked echo‐tracking system. Serum pentosidine was measured by competitive enzyme‐linked immunosorbent assay. Serum albumin, lipid profile, calcium, phosphorus, intact parathyroid hormone (iPTH), high‐sensitivity C‐reactive protein (hs‐CRP), and oxidized low‐density lipoprotein (ox‐LDL) levels were also measured. Correlation was determined by linear and multiple stepwise regression analysis. Serum pentosidine level studied in hemodialysis patients was 0.54 ± 0.13 µg/mL. No significant difference in serum pentosidine level was noted between patients with and without diabetes (0.59 ± 0.10 µg/mL vs. 0.53 ± 0.13 µg/mL, P = 0.062) as well as between patients with and without prior cardiovascular disease (CVD) history (0.56 ± 0.14 µg/mL vs. 0.53 ± 0.12 µg/mL, P = 0.206). In multivariate regression analysis, only age (β = 0.363, P < 0.001) and ox‐LDL (β = 0.262, P = 0.004) were identified as independent determinants for serum pentosidine. Serum pentosidine was significantly correlated with carotid distensibility (r = ?0.387, P < 0.001), as well as age, ox‐LDL, and hs‐CRP. After adjustment for age, blood pressure, history of diabetes, prior CVD history, lipid profile, calcium, phosphorus, iPTH, hs‐CRP, and ox‐LDL, serum pentosidine was still negatively correlated with distensibility (β = ?0.175, P = 0.044). Serum pentosidine was independently associated with carotid distensibility in hemodialysis patients. This finding suggested that the accumulation of AGE might be an important pathway in the development of arterial stiffness in end‐stage renal disease.     

Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes

Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.     

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults.

BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. METHODS: We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. RESULTS: The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm, P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm, P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P=0.047), while the association between GFR and IMT disappeared (P for trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinine.     

Association between 25-hydroxyvitamin D deficiency and cardiovascular disease in type 2 diabetic patients with mild kidney dysfunction.

BACKGROUND: A potentially modifiable and underestimated risk factor for cardiovascular disease (CVD) in subjects with kidney dysfunction is 25-hydroxyvitamin D deficiency, although the relationship between inadequate vitamin D status and manifest CVD in type 2 diabetic subjects with mild kidney impairment has not been extensively examined. METHODS: We evaluated the relationship between serum 25-hydroxyvitamin D concentrations, baseline kidney function (estimated using the modification of diet in renal disease equation) and manifest CVD (myocardial infarction, angina, ischaemic stroke, coronary revascularization or carotid endarterectomy) among 462 consecutive patients with type 2 diabetes. RESULTS: In the whole population, the mean age was 62+/-7 years, 64% were men, 76.3% had hypertension and the mean estimated glomerular filtration rate (GFR) was 94+/-33 ml/min/1.73 m(2). Kidney function was strongly and inversely associated with CVD. In multivariate logistic regression analysis, there was an inverse association between serum 25-hydroxyvitamin D concentrations and prevalent CVD [odds ratio 0.95 (95% CI 0.92-0.98; P=0.001)] in the whole population independent of baseline kidney function and other known risk factors. Additionally, the association between serum 25-hydroxyvitamin concentrations and CVD [odds ratio 0.97 (95% CI 0.94-0.99; P=0.045)] remained statistically significant in participants in the lowest estimated GFR tertile after adjustment for potential confounders. CONCLUSIONS: Decreased 25-hydroxyvitamin D concentrations are independently associated with prevalent CVD in type 2 diabetic patients with mild kidney dysfunction.     

Serum uric acid level is positively related to albuminuria in type 2 diabetic patients

Objective To investigate association between serum uric acid (SUA), albuminuria and glomerular filtration rates (eGFR) in type 2 diabetic patients. Methods A total of 220 patients were enrolled in this cross-sectional study. According to urinary albumin excretion rates, patients were divided into 3 groups: normoalbuminuria (NAU) group, microalbuminuria (MAU) group, and macroalbumnuria group (MAAU). The first two groups were subdivided at SUA＞420 μmol/L (＞357 μmol/L, female) into normouricemia group and hyperuricemia group, at eGFR＞90 ml/min into high and low renal function groups. General information, blood biochemical results were collected to analyze the association between serum uric acid, eGFR, UAER and urine albumin quantification among different groups. Results The difference of SBP, duration of diabetes (DD), Scr, SUA and eGFR between every two groups were significant (P＜0.05). SBP, DD, Scr and SUA were highest in subjects with macroalbumnuria, second in microalbuminuria group, and lowest in normoalbuminuria group, while eGFR was lowest in macroalbumnuria group and highest in normoalbuminuria group. Prevalence of hyperuricemia in macroalbumnuria group (56.9%) and microalbuminuria group (51.2%) were also significantly higher than that in normoalbuminuria group (17.5%) (all P＜0.01). The difference of UAER in the subgroups of normouricemia and hyperuricemia was more significant in microalbuminuria group than in normoalbuminuria group. eGFR was significantly lower in hyperuricemia subgroups (P＜0.01). Age and SUA were significantlg higher in subjects with low renal function compared with high eGFR (P＜0.05). Linear regression analysis indicated SUA was negatively correlated with eGFR after adjusted age, DD and UAER (β＝-0.430, P＜0.01). Binary logistic regression analysis found that increased age, DD and SUA were risk factors of microalbuminuria [β＝1.092, 95％CI(1.025, 1.163), P＜0.01; β＝1.005, 95%CI(1.001, 1.009), P＜0.05; β＝1.407, 95％CI(1.052, 1.881), P＜0.05)] andSUA, age were risk factors of early renal function decline [β＝1.015, 95％CI(1.00, 1.023), P＜0.01; β＝1.098, 95％CI(1.006, 1.199), P＜0.05]. Conclusion SUA is independently associated with albumnuria and renal function decline in type 2 DM patients.     

Mild renal insufficiency is associated with increased left ventricular mass in men, but not in women: an arterial stiffness-related phenomenon--the Hoorn Study

BACKGROUND: Mild renal insufficiency has recently been recognized as an important risk factor for cardiovascular disease (CVD). The mechanisms underlying this association are incompletely understood. Increased left ventricular mass (LVM) is an independent risk factor for CVD, which is particularly common in end-stage renal disease (ESRD) and which has been shown to be associated with mild renal insufficiency. Increased arterial stiffness has also been shown to be an independent risk factor for CVD in ESRD and has also been associated with mild renal insufficiency. We hypothesized that the association between mild renal insufficiency and increased LVM could be mediated through increased arterial stiffness, and that this may be one of the pathways linking mild renal insufficiency to CVD. We therefore investigated, in a cross-sectional population-based study, the influence of increased arterial stiffness on the association between renal function and LVM. METHODS: The study population consisted of 742 elderly individuals (373 men and 369 women). Renal function was estimated by the serum creatinine level in micromol/L; by the Cockcroft-Gault formula in mL/min and by the Modification of Diet in Renal Disease (MDRD) formula. LVM was obtained by echocardiography. RESULTS: The mean estimates of renal function in men and women were, respectively, 103.7 (SD 17.0) and 86.8 (SD 11.2) micromol/L for the serum creatinine level; 63.4 (SD 12.9) and 61.4 (SD 11.0) mL/min/1.73 m(2) for the Cockcroft-Gault formula; and 59.7 (SD 10.8) and 60.9 (SD 10.5) mL/min per 1.73 m(2) for the MDRD formula. LVM was 93.1 (SD 26.4) g/m(2) in men and 86.7 (SD 22.3) g/m(2) in women. In men, impaired renal function, as estimated by the Cockcroft-Gault and the MDRD formula, was significantly associated with greater LVM after adjustment for age, glucose tolerance, hypertension, and prior CVD [regression coefficient beta (95% CI), 1.28 (0.22 to 2.33) g/m(2) and 1.63 (0.41 to 2.86) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. However, the association between impaired renal function and increased LVM was not statistically significant after adjustment for arterial stiffness estimates [regression coefficient beta (95% CI), 0.02 (-1.60 to 1.64) g/m(2) and 0.54 (-1.25 to 2.33) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. In women, impaired renal function was not significantly associated with greater LVM. CONCLUSION: Our study shows that in a general elderly population, even mild impairment of renal function is associated with adverse changes in left ventricular structure. In men, but not in women, this leads to greater LVM, a process that may be related to increases in arterial stiffness. Importantly, these novel findings suggest that such changes occur early in the process of renal functional deterioration, which may explain, in part, the increase in cardiovascular risk in men with mildly impaired renal function.     

Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample

Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%), and twofold higher (95% CI 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles <0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage.     

人体测量学肥胖指标与微量白蛋白尿的相关性研究

目的 探讨人体测量学肥胖指标与微量白蛋白尿(microalbuminuria,MAU)的相关性.方法 在青岛市城阳区人民医院2012年流行病学调查数据库中收集调查人群1170例,留取清晨随机尿测定尿微量白蛋白(urinary albumin,UAlb)和尿肌酐(urinary creatine,UCr),计算比值(urinary albumin creatine rate,UACR)并根据UACR水平分为:正常白蛋白尿组(nornal albumin urine,NAU)(807例)和MAU组(363例),收集人体测量学指标和测定生化指标,作统计学处理.结果 ①与NAU组相比,MAU组年龄、空腹血糖(fasting blood glucose,FBG)、舒张压(diastolic blood pressure,DBP)、收缩压(systolic blood pressure,SBP)、血清尿酸(serun urinary acid,SUA)、腰围(waist circumference,WC)、腰身比(Waist to height ratio,WTHR)、腰臀比(Waist to hip ratio,WHR)均高于前者,差异有统计学意义(P＜0.05或P＜0.01);与NAU组相比,MAU 组高血糖(hyperglycemia,HG)、原发性高血压(primary hypertension,PHT)、血脂异常(dyslipidemia,DLP)及OB,尤其腹型肥胖(abdominal obesity,AOB)患病率升高,差异有统计学意义(P＜0.05或P＜0.01);②多元线性回归分析显示,对MAU贡献大小依次WTHR＞ WC＞ WHR;③采用受试者工作特征曲线(ROC)分析男性人群WTHR、WHR、WC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、0.90、91.8 cm.在女性人群中,WSR、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:O.62 ～0.65),预测切点0.52、0.84、82.5 cm.结论 ①AOB为MAU的高危人群;②WTHR为最佳预测指标,切点为0.52,其次为WC和WHR,男性切点分别为89.6 cm和0.88 cm,女性为84.5 cm和0.84 cm.     

Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria.

BACKGROUND: Intervention studies in microalbuminuric type 2 diabetic patients have demonstrated that it is possible to avoid progression to overt diabetic nephropathy and even to achieve regression to normoalbuminuria. However, the long-term impact of stabilization/regression in albuminuria on decline in glomerular filtration rate (GFR) has not been established. METHODS: 151 patients with type 2 diabetes and microalbuminuria at baseline in whom GFR was measured at least three times during 7.8 years of follow-up were divided into three groups according to the level of albuminuria during follow-up. Overt nephropathy was diagnosed as a urinary albumin excretion rate (AER) >300 mg/24 h and remission to normoalbuminuria was defined as an AER <30 mg/24 h at the last examination. RESULTS: During follow-up, 46 patients achieved remission to normoalbuminuria, 58 remained microalbuminuric and 47 patients progressed to overt nephropathy. The mean (+/- SE) yearly decline in GFR was lowest (2.3+/-0.4 ml/min/year) in patients who obtained remission, in comparison with patients remaining microalbuminuric, in whom the decline was 3.7+/-0.4 ml/min/year, and patients progressing to overt nephropathy, who had a decline in GFR of 5.4+/-0.5 ml/min/year (ANOVA, P<0.001). Start of antihypertensive treatment during follow-up was strongly associated with remission to normoalbuminuria [odds ratio: 2.32; 95% confidence interval (CI): 1.09-4.93] whereas a decrease in HbA(1c) by 1% increased the probability for remission (odds ratio: 1.48; 95% CI: 1.11-1.97). CONCLUSIONS: Remission to normoalbuminuria was associated with a decreased GFR decline during 7.8 years of follow-up in type 2 diabetic patients with microalbuminuria. Antihypertensive therapy and improved glycaemic control were independent predictors for remission.     

Superior mesenteric artery calcification is associated with cardiovascular risk factors,systemic calcified atherosclerosis,and increased mortality

Background

Atherosclerosis is a major risk factor for morbidity and mortality. However, epidemiologic data are sparse regarding risk factors for superior mesenteric artery calcification (SMAC), the association between SMAC and disease in other arterial beds, or the independent contribution of SMAC to risk of mortality. The objective of this study was to test the hypothesis that presence and extent of SMAC are associated with cardiovascular disease (CVD) risk factors, calcification in other arterial beds, and both cardiovascular and all-cause mortality, independent of classic risk factors and calcification in other arterial beds.

Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy

BACKGROUND: The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment. PATIENTS AND METHODS: Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system. RESULTS: At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02). CONCLUSION: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.     

Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance>70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.     

Association of kidney function with mortality in patients with chronic kidney disease not yet on dialysis: a historical prospective cohort study

Significant mortality occurs in populations with chronic kidney disease (CKD), but the relative contributions of lower glomerular filtration rate (GFR) itself, accompanying comorbidities, and the numerous abnormalities that develop with advancing CKD are poorly studied. We examined all-cause predialysis mortality in 861 United States veterans with CKD stage 3 to 5 not yet on dialysis. The association of GFR with mortality was analyzed by the Kaplan-Meier method, and the effects of several confounding variables on mortality were assessed in a Cox proportional-hazards model. Overall death rate was 102.1/1,000 person-years (95% CI: 90.2 to 115.6). Lower kidney function was associated with higher mortality (relative risk [95%CI] for GFR less than 20 v 41 to 60 mL/min/1.73 m2: 2.56 [1.61 to 4.07], P<0.001) after adjustment for age, race, diabetes mellitus, cardiovascular disease, smoking status, body mass index, mean arterial pressure, serum albumin, blood cholesterol, haemoglobin, and 24-hour urine protein. For every 10 mL/min/1.73 m2 lower estimated GFR, the adjusted relative risk of mortality (95% CI) was 1.28 (1.12 to 1.45), P<0.001. Lower kidney function is associated with increased mortality in patients with moderate and advanced CKD. This association is present even after adjustment for several confounders.