Association Of Urinary Albumin Excretion Research Articles

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

MO504: Urinary Albumin Excretion and Cancer Risk

Abstract BACKGROUND AND AIMS Accumulating evidence has shown that chronic kidney disease (CKD) is associated with cancer development. However, the main focus in these studies was on patients with moderately or severely impaired kidney function, rather than on patients with milder CKD defined by higher albuminuria. We hypothesized that albuminuria may have an association with cancer risk that is independent of kidney function. This study examined therefore the association between urinary albumin excretion (UAE), considered the gold standard for albuminuria assessment, and the risk of cancer incidence, independent of estimated glomerular filtration rate (eGFR). METHOD We included 8490 subjects in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. UAE was measured in two 24-h urine specimens at baseline (1997–8). Cancer incidence was ascertained by record linkage with the nationwide network and registry of histo and cytopathology in the Netherlands (PALGA). Non-melanoma skin cancer was excluded from analyses. eGFR was calculated by the 2012 CKD-EPI creatinine-cystatin C equation. Cox proportional hazards regression models were used to calculate hazard ratios [HRs, [95% confidence intervals (95% CIs)] crude and additionally adjusted for age, sex, BMI, smoking, alcohol, educational level, diabetes and baseline eGFR. To detect potential reverse causation, we excluded subjects with a follow-up time of &amp;lt;1 year and recalculated the fully adjusted models. RESULTS Overall, 50% of the included subjects were female, and the mean age was 49.8 ± 12.7 years old. Median baseline UAE was 9.4 (IQR: 6.3–17.8) mg/24 h, and the mean baseline eGFR was 94.6 ± 17.3 mL/min/1.73 m2. At baseline, subjects who had higher UAE were more likely to be male, older, have lower eGFR and to have hypertension or diabetes. During a median follow-up of 17.7 (IQR: 17.67–17.71) years, 1789 subjects developed a de novo cancer. In the age- and sex-adjusted model, every doubling of UAE was associated with a 7% (HR: 1.07, 95% CI 1.04–1.10) higher risk of overall cancer. This association remained essentially unchanged after additional multivariable adjustments, including eGFR (HR: 1.06, 95% CI 1.02–1.09). UAE was also independently associated with an increased risk of development of several site-specific cancers including urothelial cell carcinoma (HR: 1.13, 95% CI 1.02–1.25), as well as lung cancer (HR: 1.13, 95% CI 1.04–1.22), haematological cancer (HR: 1.12, 95% CI 1.00–1.25), and head and neck cancer (HR: 1.29, 95% CI 1.06–1.57). We did not observe significant associations of UAE with melanoma, breast, prostate and colorectal cancers. Additionally, the associations of UAE with overall cancer, UCC, lung cancer and head and neck cancer remained significant in the fully adjusted models after we excluded subjects with a follow-up time of &amp;lt;1 year. CONCLUSION Higher albuminuria, assessed in 24-h urine, is associated with an increased risk of overall cancer and several site-specific cancers, independent of baseline eGFR. Future studies are warranted to corroborate these findings and to examine mechanisms underlying these associations.

Albuminuria but not low eGFR is closely associated with atherosclerosis in patients with type 2 diabetes: an observational study

BackgroundThere is still controversy regarding the associations of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Therefore, it is necessary to explore the correlation between them in T2DM patients.MethodsWe conducted a survey involving 2565 T2DM patients from a single center. The study cohort was classified into three groups based on the levels of albuminuria: normal UAE (UAE < 30 mg/24 h), moderate UAE (UAE between 30 and 299 mg/24 h) and high UAE (UAE ≥ 300 mg/24 h). Additionally, the patients were divided into three separate groups according to eGFR levels, including low eGFR (eGFR < 60 ml/min/1.73 m2), intermediate eGFR (eGFR 60–89 ml/min/1.73 m2) and normal eGFR (eGFR ≥ 90 ml/min/1.73 m2) groups. Atherosclerotic lesions were compared among the three UAE and eGFR groups. Regression analyses were used to assess the associations of atherosclerotic lesions with UAE and eGFR in T2DM.ResultsAfter controlling for age, sex and diabetes duration, the prevalence of atherosclerotic plaque and stenosis were significantly increased from the normal to high UAE groups (plaque: 72.2%, 78.6% and 87.3%, respectively, p = 0.016 for trend; stenosis: 14.0%, 25.5% and 37.3%, respectively, p < 0.001 for trend). Likewise, the values of carotid intima-media thickness (CIMT) and femoral intima-media thickness (FIMT) were also obviously increased from the normal to high UAE groups (CIMT: p < 0.001 for trend; FIMT: p = 0.001 for trend). Conversely, only the FIMT value was clearly increased from the low to normal eGFR groups (p = 0.001 for trend). Fully adjusted regression analyses revealed that UAE was closely associated with the presence of atherosclerotic plaque (OR 1.20, 95% CI 1.03–1.40, p = 0.020) and stenosis (OR 1.17, 95% CI 1.01–1.35, p = 0.036), and with the values of CIMT (β 0.05, 95% CI 0.01–0.10, p = 0.029) and FIMT (β 0.07, 95% CI 0.03–0.11, p = 0.001) in T2DM patients. However, there was no significant association between eGFR levels and atherosclerotic lesions in T2DM after adjustment for multiple confounding factors.ConclusionsOverall, albuminuria rather than low eGFR is closely associated with atherosclerotic lesions in T2DM patients. Albuminuria is an independent risk factor for carotid and femoral atherosclerotic lesions in T2DM. Therefore, albuminuria may be a potential early marker to predict the development of atherosclerosis in patients with T2DM.

Association of urinary albumin excretion with central foveal thickness and intravitreal conbercept treatment frequency in patients with diabetic macular edema.

To investigate the effect of albuminuria on diabetic macular edema (DME) and the possible association between baseline urinary albumin excretion (UAE) and intravitreal conbercept (IVC) treatment frequency in DME patients. In this hospital-based retrospective study, a total of 350 in-patients with type 2 diabetes mellitus were recruited and their clinical records were reviewed. Thereafter, 52 patients identified with severe non-proliferative diabetic retinopathy (NPDR) combined with albuminuria were divided into the microalbuminuria (UAE 30-300 mg/24h) and macroalbuminuria (UAE>300 mg/24h) groups, which were compared and analyzed by both independent sample t-test and Chi-square test. Correlations between the systemic variables and the central foveal thickness (CFT) were evaluated using Spearman's correlation and linear regression analyses. Of the 52 patients with center-involved DME, 43 received an initial combined injection of conbercept (0.5 mg/0.05 mL) and triamcinolone acetonide (1 mg/0.05 mL), followed by an IVC injection, as needed. The relationship between baseline UAE and number of IVC injections during the first year of treatment was analyzed using Spearman's partial correlation. Of 350 patients, a higher incidence of DME was observed in severe non-proliferative retinopathy (NPDR) patients than that observed in other groups. By dividing the 52 patients with severe NPDR into the micro- and macro-albuminuria subgroups, significant differences in CFT, systolic blood pressure, total cholesterol and serum creatinine levels, and UAE were revealed. Furthermore, a positive liner correlation between the UAE and CFT was found. Finally, the partial correlation coefficient adjusted for either the CFT or UAE indicated that both parameters directly correlated with the number of IVC injections administered during the 12mo of follow-up. Generally, macular edema occurred in patients with severe NPDR, for whom the UAE is an independent risk predictor of DME. The baseline UAE and CFT predicted the treatment frequency of IVC injections administered in the first year for eyes with DME.

Association of urinary albumin excretion with periodontal parameters in patients with type 2 diabetes mellitus: a cross-sectional study.

Our previous pilot study using patients with type 2 diabetes mellitus in one medical clinic showed an association of urinary albumin excretion, a marker of generalized vascular dysfunction and kidney damage, with periodontitis. The purpose of this study was to confirm the association by increasing the number of patients and medical clinics. Participants were 2302 patients (59.9% males, aged 29-93years) with type 2 diabetes mellitus from 25 medical clinics. Their medical records and information about socioeconomic status and health behavior were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses were conducted to examine the association of log-transformed urinary albumin-to-creatinine ratio with periodontal parameters after adjusting for sociodemographic status, general health conditions, and health behaviors. The analyses were performed in all subjects and subjects with normoalbuminuria only. Multiple linear regression analysis showed that mean probing pocket depth (beta: 0.062), percentage of sites with probing pocket depth of 4mm or deeper (beta: 0.068), percentage of mobile teeth (beta: 0.055), and severity of periodontitis (beta: 0.049) were significantly (p < 0.05) correlated with log-transformed urinary albumin-to-creatinine ratio after adjusting for possible confounders in all subjects. However, no significant associations between urinary albumin-to-creatinine ratio and periodontal parameters were observed in subjects with normoalbuminuria only. These results suggest that periodontitis is associated with urinary albumin excretion in patients with type 2 diabetes mellitus. Collaboration between medical and dental healthcare providers is needed for treatment of diabetes and periodontitis.

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study.

We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04-1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15-1.55) for IRAE; HR 1.38 (1.06-1.79) for IURAE; HR 1.62 (1.22-2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment.

Association of night-time home blood pressure with night-time ambulatory blood pressure and target-organ damage

Night-time ambulatory blood pressure (nABP) is the most important aspect of the blood pressure profile in terms of prognosis. Novel low-cost home monitors allow automated night-time blood pressure monitoring (nHBP). This study reviewed the evidence on the association of nHBP with nABP and preclinical organ damage. Systematic review and meta-analysis. Analysis of six studies (n = 1404) showed pooled difference between nHBP and nABP (SBP/DBP) at 1.4, 95% confidence interval (CI) 0.3, 2.6/-0.2, 95% CI -0.9, 0.6 mmHg, whereas the pooled correlation coefficient between nHBP and nABP (SBP/DBP) was r = 0.70, 95% CI 0.59, 0.81/r = 0.72, 95% CI 0.67, 0.77, respectively. Two studies (n = 212) investigated the agreement between nHBP and nABP in detecting nondippers with weighted agreement 77.3% (pooled kappa 0.27, 95% CI 0.08, 0.45). Three studies (n = 954) reported on the association of left ventricular mass index with systolic nHBP and nABP (pooled correlation coefficient r = 0.36, 95% CI 0.23, 0.50 and r = 0.32, 95% CI 0.10, 0.54, respectively, P = NS for comparison). Two studies (n = 950) reported on the association of urinary albumin excretion with systolic nHBP and nABP (pooled r = 0.39, 95% CI 0.21, 0.58 and r = 0.30, 95% CI 0.06, 0.55, respectively, P < 0.01 for comparison). Two studies (n = 350) reported on the association of common carotid intima-media thickness with systolic nHBP and nABP (pooled r = 0.31, 95% CI 0.16, 0.46 and r = 0.35, 95% CI 0.17, 0.53, respectively, P = NS for comparison). The available evidence suggests that nHBP and nABP present similar values and comparable relationship with target-organ damage. Studies on the prognostic value of nHBP are needed.

Apolipoprotein B attenuates albuminuria-associated cardiovascular disease in prevention of renal and vascular endstage disease (PREVEND) participants.

Whether urinary albumin excretion relates to higher levels of atherogenic apolipoprotein B fractions in the nondiabetic population is uncertain. Such a relationship could explain, in part, the association of elevated urinary albumin excretion with cardiovascular disease risk. We assessed the relationship of urinary albumin excretion with apolipoprotein B fractions and determined whether the association of elevated urinary albumin excretion with incident cardiovascular events is modified by high apolipoprotein B fraction levels. We performed a prospective study on 8286 nondiabetic participants (580 participants with cardiovascular disease; 4.9 years median follow-up time) with fasting lipids, apolipoprotein B, and urinary albumin excretion determined at baseline. With adjustment for sex and age, micro- and macroalbuminuria were associated with increased apolipoprotein B fractions (non-HDL cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B). All four apolipoprotein B fractions modified associations of urinary albumin excretion with incident cardiovascular disease (hazard ratios for interaction terms ranged from 0.89 to 0.94 with 95% confidence intervals ranging from 0.84 to 0.99 and P values ranging from 0.001 to 0.02 by Cox proportional hazards modeling). These interactions remained present after additional adjustment for conventional risk factors, eGFR, cardiovascular history, and lipid-lowering and antihypertensive drug treatments. Such modification was also observed when urinary albumin excretion was stratified into normo-, micro-, and macroalbuminuria. We conclude that there is an association between elevated urinary albumin excretion and apolipoprotein B fraction levels and a negative interaction between these variables in their associations with incident cardiovascular events. Elevated urinary albumin excretion may share common causal pathways with high apolipoprotein B fractions in the pathogenesis of cardiovascular disease.

Association between urinary albumin excretion and coronary heart disease in black vs white adults.

Excess urinary albumin excretion is more common in black than white individuals and is more strongly associated with incident stroke risk in black vs white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear. To determine whether the association of urinary albumin excretion with CHD events differs by race. Prospective cohort study of black and white US adults aged 45 years and older who were enrolled within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 with follow-up through December 31, 2009. We examined race-stratified associations of urinary albumin-to-creatinine ratio (ACR) in 2 groups: (1) incident CHD among 23,273 participants free of CHD at baseline; and (2) first recurrent CHD event among 4934 participants with CHD at baseline. Expert-adjudicated incident and recurrent myocardial infarction and acute CHD death. A total of 616 incident CHD events (421 nonfatal MIs and 195 CHD deaths) and 468 recurrent CHD events (279 nonfatal MIs and 189 CHD deaths) were observed over a mean time of 4.4 years of follow-up. Among those free of CHD at baseline, age- and sex-adjusted incidence rates of CHD per 1000 person-years of follow-up increased with increasing categories of ACR in black and white participants, with rates being nearly 1.5-fold greater in the highest category of ACR (>300 mg/g) in black participants (20.59; 95% CI, 14.36-29.51) vs white participants (13.60; 95% CI, 7.60-24.25). In proportional hazards models adjusted for traditional cardiovascular risk factors and medications, higher baseline urinary ACR was associated with greater risk of incident CHD among black participants (hazard ratio [HR] comparing ACR >300 vs <10 mg/g, 3.21 [95% CI, 2.02-5.09]) but not white participants (HR comparing ACR >300 vs <10 mg/g, 1.49 [95% CI, 0.80-2.76]) (P value for interaction = .03). Among those with CHD at baseline, fully adjusted associations of baseline urinary ACR with first recurrent CHD event were similar between black participants (HR comparing ACR >300 vs <10 mg/g, 2.21 [95% CI, 1.22-4.00]) vs white participants (HR comparing ACR >300 vs <10 mg/g, 2.48 [95% CI, 1.61-3.78]) (P value for interaction = .53). Higher urinary ACR was associated with greater risk of incident but not recurrent CHD in black individuals when compared with white individuals. These data confirm that black individuals appear more susceptible to vascular injury.

The association of urinary albumin excretion and metabolic complications in polycystic ovary syndrome

Objective This study was planned to screen polycystic ovary syndrome (PCOS) women for albuminuria and to evaluate the association between urinary albumin excretion (UAE) and metabolic disturbances of PCOS. In addition, this is the first study in the literature evaluating the association between UAE and carotid intima–media thickness (CIMT) in PCOS cases. Study design The study population consisted of 65 PCOS women. The study was prospectively designed and performed in a university hospital. The diagnosis of PCOS was made according to the Rotterdam criteria: exclusion criteria were hyperprolactinemia, thyroid dysfunction, adrenal dysfunction, diabetes mellitus, hypertension, and pregnancy. Blood samples were collected in the follicular phase of a menstrual cycle and serum samples were analyzed for fasting glucose, insulin, and hormone and lipid profiles. Twenty-four hour urine specimens were collected for the detection of UAE. CIMT was estimated by visual assessment of the distance between the lumen–intima and intima–adventitia interfaces. Results The mean age and BMI were 23 years and 23 kg/m 2, respectively. The median UAE was 7 mg/day (range: 0.3–154 mg/day). The median UAE as micrograms of albumin per milligram of creatinine (uACR) was 5.6 (0.28–159). Regarding the uACR cutoff value (>6.93 μg/mg), significantly higher levels of triglycerides, 17 OH-progesterone, insulin resistance (HOMA index > 2.1) and increased CIMT were present in these cases. Microalbuminuria (uACR > 25 μg/mg) was present in 6.2%. In the regression analyses serum HDL-C levels were found to be independent predictor for uACR > 2 μg/mg (OR: 0.85) and estradiol levels were the independent predicting factor for uACR > 6.93 μg/mg even after adjustments for age and BMI were performed (OR:1.02). Conclusions UAE, expressed as uACR > 6.93 μg/mg, seems to be an associated sign of metabolic problems which might help in discriminating PCOS at risk of future CVD. Further studies are needed before routine use of albuminuria in PCOS cases for the detection of CVD risk.

Association of Urinary Albumin Excretion with Insulin Resistance in Japanese Subjects: Impact of Gender Difference on Insulin Resistance

To investigate the relationship between homeostasis model assessment for insulin resistance (HOMA-R) and urinary albumin excretion in Japanese and clarify gender difference in albuminuria-related insulin resistance. The subject group consisted of 752 Japanese who had no history of diabetes, hypertension or dyslipidemia. After anthropometric examination, fasting blood samples were obtained to determine plasma glucose (FPG), lipids and HOMA-R. The urinary excretion of albumin in the first void urine was expressed as the creatinine ratio (ACR, mg/gCr). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the formula for Japanese. HOMA-R showed a significant correlation with ACR, and the correlation between HOMA-R and ACR was evident in the subjects with central obesity, whereas no significant correlation was found in the non-obese subjects. There was no correlation between HOMA-R and eGFR. HOMA-R increased according to the quintile of ACR and followed a significant trend. This association was obvious in males; however, in females there was no significant trend. Multiple regression analysis revealed that HOMA-R showed a significant correlation with age, waist circumference, blood pressure and serum triglyceride. In addition, ACR exhibited an independent association with HOMA-R. The association of HOMA-R and ACR was observed only in males, and was not present in females. Microalbuminuria is associated with insulin resistance in Japanese, where central obesity might play an essential role. This association is gender-specific suggesting the involvement of sex hormones in the pathogenesis of albuminuria-related insulin resistance.

The association of urinary albumin excretion with fibrinolytic activity in patients with type 2 diabetes

Objective To examine the relationship between UAE and fibrinolytic activity in patients with type 2 diabetes.Methods 129 type 2 diabetic patients recruited and subgrouped by UAE,and the UAE,FBS,lipids,renal function and the activity of t-PA and PAI-1 were conducted in these patients and 40 health people.Results Compared to control group,the activity of PAI-1 was increased and the activity of t-PA decreased dramaticlly in type 2 diabetic group(P＜0.05);there was significant difference in the ratio of PAI-1 and t-PA between three diabetic groups(P＜0.05),of three group the ratio of PAI-1 and t-PA was most highest in the patients with macroal buminuria,and simple correlation analysis showed positive correlation between UAE and the ratio of PAI-1 and t-PA,especially in the patients with microalbuminuria(r=0.321,P＜0.05).Conclusion The UAE is closely relatedto fibrinolytic activity in patients type 2 diabetes. Key words: Diabetes,type 2; Urinary albumin excretion; Fibrinolytic activity

Relation of Microalbuminuria to Adiponectin and Augmented C-Reactive Protein Levels in Men With Essential Hypertension

Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.

Low-Grade Albuminuria and Incidence of Cardiovascular Disease Events in Nonhypertensive and Nondiabetic Individuals

Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. We examined the association of urinary albumin excretion (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49 (19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD (hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (> or =3.9 microg/mg for men, > or =7.5 microg/mg for women) experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P<0.001) and a borderline significantly increased risk of death (adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P=0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest probabilities of CVD. In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR <30 microg/mg indicates "normal" albumin excretion.

Relation of urinary albumin excretion to coronary heart disease and low renal function: Role of blood pressure

Previous studies report that urinary albumin excretion is associated with coronary heart disease (CHD). The present epidemiologic study investigated if (1) blood pressure status affects the association of urinary albumin excretion with CHD; and (2) urinary albumin excretion is associated with low renal function also. The cross-sectional association was analyzed of overnight urinary albumin excretion with prevalence of CHD (myocardial infarction and/or ischemia as defined by standard electrocardiogram) and low renal function (overnight creatinine clearance <60 mL/min) in a population sample of 1632 men and women with ages 45 to 64 years. Hypertension, hypercholesterolemia, smoking habit, and diabetes mellitus were included in analyses. CHD prevalence was in the whole sample 8.2% (N= 134), in the hypertensive subgroup 11.9% (N= 79), and in the nonhypertensive subgroup 5.7% (N= 55). For the association between urinary albumin excretion (logarithm-transformed due to skewed distribution) and CHD, the multivariate logistic coefficient with 95% CI was significant in the whole sample (+0.79, 95% CI =+0.32/+1.26, P < 0.001) and in the hypertensive subgroup (+0.97, 95% CI =+0.70/+1.24, P < 0.001), not in the nonhypertensive subgroup (-0.06, 95% CI =-0.80/+0.68, P= 0.997). Prevalence of low creatinine clearance was in the whole sample 4.0% (N= 66), in the hypertensive subgroup 4.8% (N= 32), and in the nonhypertensive subgroup 3.5% (N= 34). The logistic coefficient between urinary albumin excretion and low creatinine clearance was borderline significant in the whole sample (+0.56, 95% CI =-0.02/+1.14, P= 0.090), significant in the hypertensive subgroup (+0.73, 95% CI =+0.04/+1.42, P= 0.044), not significant in the nonhypertensive subgroup (-0.07, 95% CI =-1.25/+1.10, P= 0.913). Results support the use of urinary albumin excretion as marker of CHD and slightly reduced renal function in hypertensives.

Benefícios da atividade física no perfil lipídico de pacientes com diabetes tipo 1

Avaliamos a resposta do perfil lipídico a uma intervenção não-farmacológica de curta duração, e investigamos se alterações nas lipoproteínas estavam presentes, antes da nefropatia diabética (ND) clínica, em 46 pacientes jovens com diabetes tipo 1 (DM1), com idade de 15,5±1,5 anos submetidos a um programa de 8 dias de dieta apropriada e exercícios, durante controle glicêmico estável (glicemia média 110,3±27,1mg/dl e HbA1c 6,9±1,3%). No início, 65% dos jovens apresentavam colesterol total &gt; 160mg/dl (IC 95% 0,51-0,78), enquanto que ao final somente 38% (IC 95% 0,24-0,51) tinham tais níveis. A melhora no perfil lipídico foi ainda melhor para a fração LDL, considerando que inicialmente 67% mostravam valores acima de 100mg/dl (IC 95% 0,55-0,78) e 24% (IC 95% 0,12-0,36) ao final. Valores de HDL-colesterol subnormais (&lt; 40mg/dl) ocorreram em 38% (95% IC 0,24-0,51) e 11% (IC 95% 0,02-0,20) deles, no início e final do período. A razão albumina/creatinina média foi 9,0±8,0mg/g de creatinina. Encontramos fracas correlações entre a razão albumina/creatinina e os níveis de colesterol total (r= 0,21), LDL (r= 0,24), VLDL (r= 0,30), HDL (r= -0,17) e de triglicérides (r= 0,31). Dentro da faixa de referência de albuminúria, não foi encontrada nenhuma associação entre a excreção urinária de albumina e os níveis de lípides nos pacientes com DM1 estável. Um programa de exercícios regulares é eficaz em otimizar o perfil lipídico nestes pacientes, independentemente do controle glicêmico. Nossos dados não apoiam a hipótese de que mudanças no metabolismo lipídico precederiam a microalbuminúria no curso da ND.

Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes.

The reason for the elevation of fibrinogen concentration in diabetic patients with nephropathy is not known so far. In order to elucidate the mechanism of such an increase in fibrinogen levels, we investigated haemorheological and inflammatory markers in type 2 diabetic patients in a cross-sectional design. Thirty-two non-smoking type 2 diabetic patients (13 women, 19 men; body mass index 29.1+/-5.4 kg/m2, age 62.8+/-12.1 years) were investigated. Patients with C-reactive protein levels >1.5 mg/dl were excluded from the study. Concentration of fibrinogen was measured by immunonephelometry, C-reactive protein by immunoturbidimetry, and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay, and viscosity of plasma and of whole blood was determined by rotation viscosimetry. Concentrations of inflammatory parameters were well correlated with each other (p<0.05 for all correlations): IL-6 with C-reactive protein (r=0.48), and C-reactive protein with fibrinogen (r=0.41). While no associations were found with concentrations of C-reactive protein or IL-6, urinary albumin excretion was correlated with erythrocyte sedimentation rate (r=0.47) and with fibrinogen concentration (r=0.39; p<0.05). In patients with type 2 diabetes mellitus, urinary albumin excretion was not associated with concentrations of IL-6 or C-reactive protein. These results suggest an IL-6-independent mechanism for increased fibrinogen levels and erythrocyte sedimentation rate in type 2 diabetic patients with increased urinary albumin excretion.