A newly estimated glomerular filtration rate is independently associated with arterial stiffness in Japanese patients.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, and thus is a major worldwide public health problem. Recently, an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation for Japanese patients was proposed by the Japanese Society of Nephrology. However, the role of eGFR in the assessment of atherosclerosis is not well understood in Japanese patients. We analyzed the relationship between eGFR and severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 647 adult Japanese patients. baPWV correlated significantly and positively with age, hypertension, diabetes, prior cardiovascular disease, blood pressure, pulse pressure and heart rate, and negatively with eGFR (r=-0.405, p<0.0001). A multiple regression analysis revealed that baPWV correlated independently with eGFR. Furthermore, there was a stepwise increase in baPWV, corresponding to advances in CKD through stages 1 to 5. When CKD stage 3 was divided at eGFR 45 mL/min/1.73 m2, the baPWV of stage 3b (eGFR 30 to 44) was significantly higher than that of stage 3a (eGFR 45 to 59) independent of traditional risk factors, suggesting that an eGFR of 45 mL/min/1.73 m2 may be a critical cut off value to predict arterial stiffness in CKD. In conclusion, the newly proposed eGFR is significantly associated with arterial stiffness, independent of traditional risk factors for cardiovascular disease.     

Hyperhomocysteinaemia is not associated with isolated crural arterial occlusive disease: The Hoorn Study

OBJECTIVES: Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease (PAD). The localization of peripheral arterial disease is clinically relevant, because proximal (aortoiliac and femoropopliteal) disease is associated with a particularly poor overall prognosis, whereas isolated distal (i.e. crural) disease is associated with a better overall prognosis. The aim of the study was to investigate whether the strength of the association between hyperhomocysteinaemia and peripheral arterial disease differs according to the localization of the anatomical obstruction. DESIGN: Fasting serum total homocysteine (tHcy) was measured in an age-, sex- and glucose-tolerance stratified random sample (n = 631) of a 50- to 75-year-old general Caucasian population. History of a peripheral arterial reconstruction was recorded. Aortoiliac, femoropopliteal and crural arterial obstructions were registered by means of Doppler flow velocity curves. RESULTS: The median serum tHcy level was 12.2 micromol L-1 (interquartile range: 10.0-15.3) in men and 10.7 micromol L-1 (interquartile range: 9.0-13.3) in women. The prevalences of aortoiliac, femoropopliteal and crural obstructions were 2.1%, 2.7% and 11.9%, respectively. After adjustment for age, sex, systolic blood pressure, current smoking, serum cholesterol and diabetes mellitus, the odds ratios (95% confidence interval) per 5 micromol L-1 tHcy increment were 1.41 (1.05-1.89) for aortoiliac, 1.03 (0. 70-1.52) for femoropopliteal and 0.82 (0.59-1.15) for crural obstructions. Finally, diabetes mellitus, HbA1c and current smoking were significantly associated with crural and femoropopliteal disease, whereas systolic blood pressure was significantly associated with aortoiliac obstructions. CONCLUSIONS: The present study indicates that hyperhomocysteinaemia is associated with aortoiliac but not with isolated crural arterial occlusive disease.     

Albuminuria rather than glomerular filtration rate is associated with vascular endothelial function in patients with type 2 diabetes

AimsAlbuminuria and reduced glomerular filtration rate (GFR) are manifestations of diabetic kidney disease and are both shown to be associated with cardiovascular outcomes. However, the differential association of albuminuria and reduced GFR with endothelial dysfunction, an early feature of atherosclerotic vascular damage, remains unclear. In this study, we investigated the association between albuminuria or estimated GFR (eGFR) and flow-mediated dilatation (FMD), a marker of endothelial function, in patients with type 2 diabetes.MethodsThis study included 633 patients with type 2 diabetes. The FMD of the brachial artery was measured by ultrasonography. Albuminuria was evaluated by urinary albumin-to-creatinine ratio (ACR).ResultsThe mean FMD and eGFR, and the median value of ACR were 6.7%, 66.5 mL/min/1.73m² and 12.5 mg/g creatinine, respectively. Impaired FMD was found in patients with advanced stages of chronic kidney disease based on both GFR and albuminuria categories. Multivariate analysis after adjusting for potential confounders revealed that ACR, but not eGFR, was significantly and inversely associated with FMD.ConclusionsAlbuminuria is associated with FMD, independently of traditional cardiovascular risk factors in patients with type 2 diabetes. This study suggests a close relationship between albuminuria, rather than reduced GFR, and endothelial dysfunction in type 2 diabetes.     

Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study

Summary Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this study was to investigate whether microalbuminuria is part of a cluster of risk factors, the insulin resistance syndrome (IRS), or whether it is only associated with, and presumably a complication of, hypertension and non-insulin-dependent diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random sample from a 50–75 year old general population (n = 622) was investigated. The urinary albumin-to-creatinine ratio was measured in an early morning spot urine sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater than 2.0 mg/mmol. We considered, as IRS-related variables, fasting hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL-cholesterol in the lowest and / or levels of triglyceride in the highest tertile. Fasting insulin levels, IR and WHR were divided into tertiles; the highest tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance-adjusted analyses showed microalbuminuria to be significantly associated with hypertension, NIDDM and WHR. In multiple logistic regression analyses, microalbuminuria showed independent associations with hypertension, NIDDM and WHR, with odds ratios (ORs [95 % confidence interval]) of 3.33 (1.86–5.96), 2.26 (1.14–4.48) and 2.49 (1.09–5.70), respectively. No associations were found with impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple logistic regression analyses in diabetic and non-diabetic subjects separately showed that microalbuminuria was independently associated only with hypertension (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was associated with hypertension, NIDDM and WHR and not with other variables of the IRS. It is therefore likely that microalbuminuria is a complication of hypertension and NIDDM, and not an integral part of the IRS. [Diabetologia (1998) 41: 694–700] Received: 7 August 1997 and in revised form: 5 January 1998     

Relation between estimated glomerular filtration rate and composition of coronary arterial atherosclerotic plaques

It is well known that chronic kidney disease is a risk factor for atherosclerosis. The present study was conducted to identify any relation between the estimated glomerular filtration rate (eGFR) and coronary plaque characteristics using integrated backscatter intravascular ultrasound (IB-IVUS), which can detect coronary plaque composition. We performed IB-IVUS for 201 consecutive patients undergoing percutaneous coronary intervention, and they were divided into 3 groups according to the eGFR values (group 1 [n = 20], ≥90 ml/min/1.73 m(2); group 2 [n = 123], 60 to 90 ml/min/1.73 m(2); and group 3 [n = 58], <60 ml/min/1.73 m(2)). Coronary plaques in nonculprit lesions on 3-dimensional analysis were evaluated using IB-IVUS. The baseline characteristics were similar, except for older age and a greater prevalence of men in group 3. IB-IVUS showed a percentage of lipid volume of 44.7 ± 5.0% in group 1, 53.6 ± 6.2% in group 2, and 63.5 ± 6.2% in group 3 (p <0.01), with a corresponding percentage of fibrous volume of 53.9 ± 4.9%, 45.1 ± 6.0%, and 35.3 ± 6.1%, respectively (p <0.01). The eGFR correlated significantly with both parameters (r = -0.68, p <0.001 and r = 0.68, p <0.001, respectively). In conclusion, lower eGFR levels were associated with greater lipid and lower fibrous contents, contributing to coronary plaque vulnerability.     

老年高血压患者动态动脉硬化指数与估测肾小球滤过率的相关性

目的 观察老年高血压患者动态动脉硬化指数（ AASI）与估测肾小球滤过率（eGFR）的相关性,探讨以AASI大小反应的动脉硬化程度在老年高血压患者肾功能受损中的作用.方法 218例行24小时动态血压检测血肌酐水平基本正常的老年高血压患者,根据文献方法计算AASI,以AASI≤0.55或AASI＞ 0.55分为两组,比较各组间eGFR的差异,以及运用Pearson相关分析及多元线性回归分析eGFR与AASI及年龄、平均收缩压、平均舒张压、血肌酐水平等因素的相关性.结果 与AASI≤0.55组比较,在AASI＞ 0.55组中eGFR值明显降低（P＜0.001）.Pearson 相关分析显示,eGFR与AASI呈负相关（r=-0.624,P＜0.001）,控制年龄、平均收缩压、平均舒张压、平均脉压、血肌酐水平等因素后,偏相关分析显示,eGFR仍与AASI显著相关（r=-0.343,P＜0.001）.多元逐步回归分析显示,eGFR 与肌酐水平、AASI独立相关,标准化偏回归系数分别为-0.770、-0.240,P＜0.001.结论 在老年高血压患者,AASI与eGFR呈独立负相关,AASI值增加是老年高血压患者早期肾功减退的独立危险因素.     

High glomerular filtration rate is associated with impaired arterial stiffness and subendocardial viability ratio in prediabetic subjects

Background and aimsHigh glomerular filtration rate (HGFR) is associated with cardiovascular damage in the setting of various conditions such as obesity and diabetes. Prediabetes was also associated with increased GFR, however, the association between prediabetes, HGFR and cardiovascular damage has not been investigated. In this study, we investigated the association between HGFR and early markers of cardiovascular disease in subjects with prediabetes.Methods and resultsAugmentation pressure (Aug), augmentation index (AIx), subendocardial viability ratio (SEVR), pulse wave velocity (PWV), intima-media thickness (IMT) and estimated GFR (eGFR) were evaluated in 230 subjects with prediabetes. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration formula. HGFR was defined as an eGFR above the 75th percentile.Prediabetic subjects were divided into two groups according to presence/absence of HGFR: 61 subjects with HGFR and 169 subjects without HGFR. Subjects with HGFR showed higher Aug, AIx and lower SEVR compared with prediabetic subjects with lower eGFR (14.1 ± 7.2 vs 10.8 ± 6.2, 32.9 ± 12.7 vs 27.6 ± 11.7, 153.5 ± 27.8 vs 162 ± 30.2, p < 0.05). No differences were found in PWV and IMT values between the two groups. Then, we performed multiple regression analysis to test the relationship between Aug, SEVR and several cardiovascular risk factors. In multiple regression analysis Aug was associated with age, systolic blood pressure (BP), HOMA-IR and eGFR; the major determinants of SEVR were systolic BP, HOMA-IR and eGFR.ConclusionSubjects with prediabetes and HGFR exhibited an increased Aug, AIx and a reduced SEVR. These alterations are associated with eGFR, insulin resistance and systolic BP.     

Rapid decline in estimated glomerular filtration rate is common in adults with sickle cell disease and associated with increased mortality

We evaluated the prevalence of rapid decline in kidney function, its potential risk factors and influence upon mortality in sickle cell disease (SCD) in a retrospective single-center study. Rapid decline of kidney function was defined as estimated glomerular filtration rate (eGFR) loss of >3·0 ml/min/1·73 m² per year. A multivariable logistic regression model for rapid eGFR decline was constructed after evaluating individual covariates. We constructed multivariate Cox-regression models for rapid eGFR decline and mortality. Among 331 SCD patients (median age 29 years [interquartile range, IQR: 20, 41]; 187 [56·5%] female) followed for median 4·01 years (IQR: 1·66, 7·19), rapid eGFR decline was noted in 103 (31·1%). History of stroke (odds ratio [OR]: 2·91, 95% confidence interval [CI]: 1·25–6·77) and use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (OR: 3·17, 95% CI: 1·28–7·84) were associated with rapid eGFR decline. The rate of eGFR change over time was associated with mortality (hazard ratio [HR]: 0·99, 95% CI: 0·984–0·995, P = 0·0002). In Cox-regression, rapid eGFR decline associated with mortality (HR: 2·07, 95% CI: 1·039–4·138, P = 0·04) adjusting for age, sex and history of stroke. Rapid eGFR decline is common in SCD and associated with increased mortality. Long-term studies are needed to determine whether attenuating loss of kidney function may decrease mortality in SCD.     

Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not; The Hoorn Study

BACKGROUND: Type 2 diabetes (DM2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. Impaired endothelial synthesis of nitric oxide (NO) is an important feature of atherothrombosis and can be estimated from endothelium-dependent flow-mediated dilation (FMD). It is controversial whether or not FMD is impaired in DM2 and IGM. We investigated this issue in a population-based setting. METHODS AND RESULTS: In the study population (n = 650; 246 with normal glucose metabolism (NGM), 135 with IGM and 269 with DM2; mean age: 67.6 years), FMD and endothelium-independent nitroglycerine-mediated dilation (NMD) were ultrasonically estimated from the brachial artery and expressed as the absolute change in diameter in mm. The increase in diameter (mean +/- standard deviation) in NGM, IGM and DM2 was 0.19 +/- 0.15, 0.19 +/- 0.18 and 0.13 +/- 0.17 MD and 0.45 +/- 0.21, 0.43 +/- 0.24 and 0.45 +/- 0.25 for NMD. After adjustment for age, sex, baseline diameter and percentage increase in peak systolic velocity, DM2, as compared to NGM, remained associated with impaired FMD (regression coefficient beta (95%CI)) as compared to NGM, -0.06 mm (-0.09 to -0.03). IGM was not associated with impaired FMD (beta, 0.01 mm (-0.02 to 0.04)). Additional adjustment for conventional cardiovascular risk factors did not alter these associations. Hyperglycemia or hyperinsulinemia explained 2% of the association between DM2 and FMD. NMD was not associated with glucose tolerance. CONCLUSIONS: This study shows that DM2 is independently associated with impaired FMD. Hyperglycemia and hyperinsulinemia contribute minimally to this association. Impaired FMD may therefore, in part, explain the increased cardiovascular disease risk in DM2, whereas the normal FMD in IGM suggests that other forms of endothelial dysfunction are important in explaining the increased cardiovascular disease risk in IGM.     

Increase in collagen turnover but not in collagen fiber content is associated with flow-induced arterial remodeling

BACKGROUND: Degradation and synthesis of collagen are common features in arterial geometrical remodeling. Previous studies described an association between arterial remodeling and an increase in collagen fiber content after balloon injury. However, this does not exclude that the association between collagen content and remodeling depends on arterial injury since the association of collagen fiber content and arterial remodeling, without arterial injury, has not been investigated. The aim of the present study was to study the relation between flow-induced arterial geometrical remodeling, without arterial injury, and collagen synthesis and degradation, collagen fiber content and cell-migration-associated moesin levels. METHODS AND RESULTS: In 23 New Zealand White rabbits an arteriovenous shunt (AV shunt) was created in the carotid and femoral artery to induce a structural diameter increase or a partial ligation (n = 27 rabbits) to induce a diameter decrease. In both models, arterial remodeling was accompanied by increased procollagen synthesis, reflected by increased procollagen mRNA or Hsp47 protein levels. In both models, however, no changes were detected in collagen fiber content. Active MMP-2 and moesin levels were increased after AV shunting. CONCLUSIONS: Collagen synthesis and MMP-2 activation were associated with arterial remodeling. However, a change in collagen fiber content was not observed. These results suggest that, during flow-induced geometrical arterial remodeling, increases in collagen synthesis are used for matrix collagen turnover and cell migration but not to augment collagen fiber content.     

Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration

Background

The aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients.

Method

Patients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated.

Result

In total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116–8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ.

Conclusion

We provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations.

Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study

Aims/hypothesis. The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA_{1 c} in a population-based cohort of 2363 older (50–75 years) subjects, without known diabetes. Methods. Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. Results. During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA_{1 c} values were, even within the non-diabetic range, associated with an increased risk (p for linear trend < 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p < 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p < 0.05). Conclusion/interpretation. High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA_{1 c} values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes. [Diabetologia (1999) 42: 926–931] Received: 18 January 1999 and in revised form: 22 April 1999     

GlycA,a marker of protein glycosylation,is related to albuminuria and estimated glomerular filtration rate: the ELSA-Brasil study

Background

Systemic inflammation has been implicated in several chronic diseases. GlycA is a new nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation that reflects protein glycosylation. We evaluated the association of GlycA with albuminuria and eGFR in the ELSA-Brasil Study.

Methods

The cross-sectional association between GlycA (automated NMR LipoProfile(®) test spectra, LabCorp, Raleigh, NC), and overnight 12 h–albuminuria and CKD-EPI eGFR was evaluated among 5050 participants.

Results

GlycA was higher among older, women, smokers, alcohol abstemious, obese and in those with diabetes, hypertension or dyslipidemia. In addition, both eGFR and albuminuria were associated to GlycA. In linear regression, GlycA was independently associated with log albuminuria (B 0.03; 95%CI 0.02–0.04, P?<?0.0001, per 1sd increase) and inversely related to eGFR (B -0.53; 95%CI -0.99 – -0.07, P?<?0.02), even after adjustments including hsCRP. In logistic regression, GlycA was independently related to the risk of A2 or A3 albuminuria (OR 1.42, 95%CI 1.27–1.57, p?<?0.0001, per 1sd increase), of having an eGFR?<?60 ml/min/1.73m² (OR 1.26, 95%CI 1.12–1.41, p?=?0.0003, per 1 sd) or of a combined diagnosis of both conditions (OR 1.35, 95%CI 1.23–1.46, p?<?0.0001, per 1 sd). In the ROC curve, GlycA had a higher AUC in comparison to hsCRP (AUC 0.67 vs. 0.62, p?=?0.06) for the association with albuminuria A2 or A3.

Conclusions

The present study demonstrates that GlycA is associated with albuminuria and eGFR, independently of major risk factors for CKD progression, including (and with a stronger association than) hsCRP. GlycA should be further evaluated in CKD progression.