Normoalbuminuria Group Research Articles

The role of renal damage on cardiac remodeling in patients with diabetic nephropathy

Cardiovascular damage and diabetic nephropathy are major complications in patients with Type 2 diabetic nephropathy (T2DN); however, the role of renal damage on cardiac remodeling is not yet fully known. A retrospective research was conducted in 254 T2DN patients. All were divided into three groups according to urinary albumin excretion (UAE): the normoalbuminuria group (UAE < 30 mg/g, n = 18), the microalbuminuria group (UAE 30 - 300 mg/g, n = 99) and the macroalbuminuria group (UAE > 300 mg/g, n = 137). The parameters of cardiac remodeling, left atrial diameter (LAD), left ventricular diameter at the end of diastole (LVDd), interventricular septum (IVS), posterior wall of left ventricle (PWLV) and ejection fraction (EF), were determined by Doppler echocardiography. The effects of renal damage on cardiac remodeling were analyzed. Among the 254 patients, LAD and LVDd enlargement was found in 180 (70.86%) and 53 (20.86%) patients, respectively; 46 cases (18.11%) suffered from both LAD and LVDd enlargement. Compared with normal LAD/LVDd groups, creatinine clearance (Ccr) and hemoglobin (Hb) were significantly lower in the left atrial (LA) and left ventricular (LV) dilated groups. LAD was positively correlated with mesangial sclerosis, tubular-interstitial lesions, interstitial fibrosis, as well as tubular basement membrane thickness (r = 0.273, 0.208, 0.176, 0.155, p < 0.05, respectively). Moreover, in comparison to patients with LA enlargement, more severe renal damage was detected in patients with LV enlargement. There is a strong correlation between echocardiographic parameters and kidney lesions in patients with T2DN in China; the more severe the renal damage, the more severe the cardiac structural alteration. Renal damage contributes to cardiac remodeling, which may provide new insights into the pathogenesis of cardiovascular complications ,in diabetes mellitus.

Urinary podocalyxin positive-element occurs in the early stage of diabetic nephropathy and is correlated with a clinical diagnosis of diabetic nephropathy

AimsWe tested whether urinary podocalyxin-positive element (PCX+EL) can be a marker of early stage of diabetic nephropathy (DN). MethodsDN patients (n=68) and health controls (n=28) were enrolled in this study. Patients were classified into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Urinary PCX+EL, serum cystatin C (Scys C) and serum creatinine (SCr) were quantified, and correlations between urinary PCX+EL and urinary albumin, Scys C and SCr were examined. The comparison of diagnosis efficiency among urinary PCX+EL, Scys C and SCr was made by receiver operating characteristic (ROC) analysis. ResultsUrinary PCX+EL, Scys C and SCr significantly increased in DN patients compared with controls. Urinary PCX+EL increased significantly in all three patients groups compared with controls. However, the concentration of Scys C and SCr did not increase in normoalbuminuria group. Urinary albumin, Scys C and SCr correlated with urinary PCX+EL. ROC curve analysis indicated that area under the curve (AUC) of urinary PCX+EL (0.966) is higher than that of Scys C (0.857) and SCr (0.726) for discriminating nephropathy between DN patients and controls. ConclusionUrinary PCX+EL may be a noninvasive marker for the early stage of DN.

Effect of Losartan on Prevention and Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes

Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30–299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to ≤60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min. Another outcome was differences in glomerular structure at end of treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95% CI, 0.12–1.99). Differences in mesangial fractional volume were not estimated in the combined albuminuria groups because of an interaction with treatment assignment. In separate analyses, mesangial fractional volume was lower in subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P = 0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86). Treatment with losartan may preserve some features of kidney structure in American Indians with type 2 diabetes and microalbuminuria.

Impaired antioxidant action of high density lipoprotein in patients with type 1 diabetes with normoalbuminuria and microalbuminuria

AimsPatients with type 1 diabetes, in the absence of chronic complications, have serum concentrations of high density lipoprotein cholesterol (HDL-C) similar to the general population. However, their HDL particles may be dysfunctional. We aimed to evaluate the antioxidant effect of HDL2 and HDL3 obtained from Caucasian males with type 1 diabetes with normoalbuminuria and microalbuminuria. MethodsTwenty Caucasian men with type 1 diabetes (10 with normoalbuminuria and 10 with microalbuminuria) and 10 healthy Caucasian men participated in the study. Lipoproteins were obtained by density gradient ultracentrifugation. The antioxidant effect of HDL was assessed by measuring lipid hydroperoxide (LOOH) concentration after 3h of pooled LDL oxidation catalyzed by 5μM CuSO4 in the absence or presence of HDL2 or HDL3. ResultsThe control, normoalbuminuria, and microalbuminuria groups had similar HDL-C concentration and estimated glomerular filtration rate. Glycemic control was similar between diabetes groups (HbA1c 8.1±0.9% and 8.3±0.7%, P=0.70), but estimated glucose disposal rate was lower in patients with microalbuminuria (8.0±0.6 and 4.5±1.1mg/kg/min, P<0.01). The relative antioxidant effect of HDL2 from control, normoalbuminuria, and microalbuminuria groups were 92.8±2.4%, 85.4±1.7%, and 74.2±4.6%, respectively (P<0.01), and the HDL3 effect were 95.0±2.2%, 86.4±4.4%, and 75.3±4.2%, respectively (P<0.01). ConclusionBoth HDL2 and HDL3 inhibited LOOH formation in copper-catalyzed oxidation of LDL in vitro. Overall, this antioxidant effect was lower in Caucasian men with type 1 diabetes, and was further compounded in those with microalbuminuria.

Umbilical Pulsatility Index is Associated with Fetalacidemia in Type 1 Diabetic Pregnancies

This study was designed to test umbilical indices and establish a reference in pregnancies complicated by type 1 diabetes mellitus, and to correlate the pulsatility index to other clinical parameters. We included consecutively 129 type 1 diabetic pregnant women during a five year period. During their pregnancy HbA1c, electrolytes, uric acid, diurnal blood pressure was measured and 24-h urine collected for measurement of albumin excretion rate. Umbilical blood flow measurements were done routinely from week 32 and started before week 32 on indication. Resistance and pulsatility indices and systolic-diastolic ratio were measured. The weekly repeated measurements from gestational 32 to 34 had the lowest levels of pulsatility index in the normoalbuminuria group and highest in the micro- and macroalbuminuria group combined (p = 0.01). We found an association of pulsatility index and umbilical pH (p<0.006). Even when adjusted for birth weight ratio, blood pressure, albumin excretion rate and HbA1c the association of pulsatility index and umbilical pH persisted (r = -0.30, p = 0.016). Glycemia expressed as HbA1c was associated with pulsatility index at nearly all measurements from week 31 to 35 and associated with albumin excretion rate. We were not able to predict adverse feto-maternal outcome in our pregnancies using umbilical indices. The correlation of pulsatility index and HbA1c underlines the importance of glycemic status during pregnancy. Albumin excretion rate affects the level of the umbilical pulsatility index.

Assessment of Carotid Atherosclerosis in Type 2 Diabetes Mellitus Patients with Microalbuminuria by High-Frequency Ultrasonography

The aim of this study is to evaluate carotid atherosclerosis in patients of type 2 diabetes mellitus with microalbuminuria (MA) by high-frequency ultrasonography. Two hundred and fifty patients of type 2 diabetes mellitus were divided into two groups according to urinary albumin excretion rate (UAER): normoalbuminuria group (130 cases) and microalbuminuria group (120 cases). The intimal-medial thickness (IMT) and the atherosclerotic plaques of carotid artery were observed in both groups by high-frequency ultrasound. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. The values of IMT of microalbuminuria group were significantly higher than those of normoalbuminuria group (P < 0.05). In univariate analysis, IMT was positively and significantly associated with age (r = 0.265, P < 0.05), waist circumference (r = 0.263, P < 0.05), body mass index (r = 0.285, P < 0.05), systolic blood pressure (r = 0.276, P < 0.05), UAER (r = 0.359, P < 0.05), HbA1c (r = 0.462, P < 0.05) and, duration of diabetes (r = 0.370, P < 0.05). In multivariate linear regression analysis, UAER and HbA1c were independent predictors of IMT (P < 0.05 for all). In the two groups, the rate of soft plaques was higher than that of dense plaques and calcified plaques. In conclusion, there is a significant association between microalbuminuria and IMT which is regarded as the early sign of carotid atherosclerosis in type 2 diabetic patients.

Does microalbuminuria at mid‐pregnancy predict development of subsequent pre‐eclampsia?

The aim of this study was to evaluate microalbuminuria at mid-pregnancy, using the albumin-to-creatinine ratio (ACR), as a predictor of pre-eclampsia. This prospective observational study was carried out on 144 normotensive women, aged<35 years, body mass index<25kg/m², and live singleton pregnancy between 24 and 28 weeks. In all, the ACR was measured in spot random urine samples. Normoalbuminuria was an ACR of <30 mg/g, whereas microalbuminuria was an ACR of 30-299 mg/g creatinine. All were followed till delivery. Primary outcome was the development of pre-eclampsia. The secondary outcome measures were preterm births and neonatal birthweight. Statistical analysis was done with Fisher's exact and t-tests. Of all, 77.1% (111/144) had normoalbuminuria and 22.9% (33/144) had microalbuminuria. Of 33 microalbuminuric women, the mean blood pressure was significantly higher in those who subsequently developed pre-eclampsia (P<0.001). The mean ACR (mg/g) in this cohort was 60.6±29.4. The mean ACR (mg/g) in women who subsequently developed pre-eclampsia was significantly higher than in women who remained normotensive (P=0.003). Of 33 microalbuminuric women, 12 (36.4%) developed pre-eclampsia, and eight (24.2%) had preterm births. The mean birthweight (kg±standard deviation) was significantly lower in the microalbuminuria group (2.45±0.6) as compared to the normoalbuminuria group (2.8±0.37), P<0.001. Microalbuminuria in mid-pregnancy may be a significant predictor of development of subsequent pre-eclampsia, preterm birth and low-birthweight babies.

Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes

Increased albuminuria is a hallmark of early diabetic nephropathy, whereas the role of immunoglobulins (Igs), such as IgG (its 1-4 subtypes), IgA, and IgM, different in charge and size, has not been examined in early nephropathy in the past due to lack of a sensitive and reliable method. Our study group consisted of subjects with type 1 diabetes (T1D) and normoalbuminuria (n = 78), microalbuminuria (n = 78), and of 75 healthy subjects (HS). A Luminex-based immunoassay (1,000 time more sensitive than nephelometry-based method) was validated for the urine matrix and used for the measurements of IgG1-4, IgA, and IgM in our study groups. The Luminex-based assay detected Igs in 87% of HS subjects and in 100% of T1D subjects. Recovery of known amounts of Igs added to urine was 92-118%. In the normoalbuminuria group, urinary concentrations of albumin, IgG2, IgA, and IgM were significantly higher than in HS, whereas in the microalbuminuria, further elevation of IgG2, IgG4, and IgA was the most pronounced. In all three groups, fractional excretion of Igs was at least 100 times lower than that of albumin. Fractional excretion of IgG2 was the highest among all Igs. We validated a sensitive method for measuring Igs in urine using Luminex. We found that elevated concentrations of Igs, particularly in IgG2 and IgA, is present in subjects with T1D and no proteinuria. Elevation of those particular Ig subtypes suggests a contribution of novel mechanisms in early diabetic nephropathy, different from charge and size barrier impairment.

Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients

AimThe aim of this study was to evaluate the association of urinary tubular markers, interleukin-18 (IL-18) and angiotensinogen with albuminuria in early nephropathy of type 2 diabetics. MethodsUrine levels of tubular markers (kidney injury molecule [KIM]-1, neutrophil gelatinase-associated lipocalin [NGAL] and liver-type fatty acid-binding protein [L-FABP]), proinflammatory marker (IL-18), and a marker of intrarenal renin-angiotensin system (RAS) status (angiotensinogen) were determined in 118 patients with type 2 diabetes mellitus and 25 non-diabetic controls with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. ResultsUrinary levels of KIM-1, NGAL, IL-18 and angiotensinogen were significantly higher in macroalbuminuria group compared with control and normo- and microalbuminuria groups but not significantly different between control and normoalbuminuria group. Urinary tubular markers were positively correlated with urinary IL-18 and angiotensinogen, respectively. The urinary albuminuria was correlated with all investigated urinary markers in univariate analysis. After adjusting for several clinical parameters, urinary KIM-1, NGAL and angiotensinogen were significantly associated with albuminuria. ConclusionsThe results of this study suggest that urinary tubular markers may be independently associated with albuminuria in the early stage of nephropathy in type 2 diabetics (eGFR ≥60mL/min/1.73m2) and may reflect inflammatory processing and the activation of the intrarenal RAS.

Albuminuria independently predicts cardiovascular and all-cause mortality in a middle-aged and elderly Chinese population

Aim. To investigate the relationship between albuminuria and mortality in a middle-aged-to-elderly Chinese population. Methods. A total of 2,344 individuals aged over 40 in the same district were interviewed and followed up for 4 years. Information on survival or cause of death was recorded. A total of 2,181 participants with detailed information were finally recruited. Baseline overnight urine samples were obtained to measure urinary albumin and creatinine. The urinary albumin excretion rate was expressed as albumin-to-creatinine ratio (ACR). Participants were divided into three groups, according to their ACR: normoalbuminuria (ACR < 30 mg/g), microalbuminuria (≥ 30 – < 300 mg/g ACR) and macroalbuminuria (ACR ≥ 300 mg/g). The Cox proportional hazard model was used to analyze the relationships between albuminuria and cardiovascular and all-cause mortalities. Results. Seventy-seven deaths with known causes were registered. The prevalences of microalbuminuria and macroalbuminuria at baseline were 8.3% and 1.6%, respectively. Cardiovascular mortalities in the normoalbuminuria, microalbuminuria and macroalbuminuria groups were 2.4, 11.0, and 36.8/1,000 person years (pyrs) respectively, and all-cause mortalities were 6.9, 20.6, and 58.8/1,000 pyrs. After adjusting for confounding factors, the relative risks (RR) of cardiovascular mortality were 2.72 (95% CI, 1.06–4.20) in the microalbuminuria group, and 4.87 (95% CI, 2.46–9.45) in the macroalbuminuria group. Adjusted RRs for all-cause mortality were 2.01 (95% CI, 0.96–4.77) and 3.76 (95% CI, 1.52–7.15) in the two groups, respectively. Conclusion. Albuminuria is a useful predictor of cardiovascular mortality and all-cause mortality in the general population.

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and normoalbuminuria group (n = 43), and 34 age- and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.

Elevated Admission Microalbuminuria Predicts Poor Myocardial Blood Flow and 6‐Month Mortality in ST‐Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Microalbuminuria (MA) is considered a major risk factor predisposing to cardiovascular morbidity and mortality. Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by MA have been well described. However, data regarding admission MA and coronary and myocardial flow are scant. The aims of this study were to evaluate the effects of admission MA on coronary blood flow and prognosis in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. Did elevated admission microalbuminuria predict poor myocardial blood flow and 6-month mortality in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention? A total of 247 patients undergoing primary PCI for STEMI within 12 hours after symptom onset were studied. Patients were divided into 2 groups according to admission urinary albumin extraction rate (UAER): (1) an MA group (UAER 20-200 µg/min), and (2) a normoalbuminuria (NA) group (UAER < 20 µg/min). Microalbuminuria was observed in 108 patients. Univariate analyses showed statistical differences between the NA and MA groups in serum creatine level, plasma glucose level, and peak creatine kinase level on presentation. Thrombolysis In Myocardial Infarction (TIMI) flow grades (TFGs) 0-2 in the MA group were more frequent (9.4% vs 21.2%, P < 0.05) than in the NA group, and corrected TIMI frame count was higher (23.9 ± 18.5 vs 29.8 ± 23.5, P < 0.05). Admission MA was an independent predictor of poor myocardial perfusion (adjusted relative risk: 3.14, 95% confidence interval: 0.99-6.78) and a higher rate of 6-month mortality in STEMI patients undergoing primary PCI (adjusted relative risk: 1.58, 95% confidence interval: 0.74-3.39). Admission MA levels are associated with impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI.

Pattern of urinary albumin excretion in normotensive young and adolescent Indian women with polycystic ovary syndrome

Objective:Polycystic ovarian syndrome (PCOS) is a clinically heterogeneous endocrine disorder affecting up to 4–8% of women of reproductive age. The aim of this study was to evaluate the presence of microalbuminuria in women with PCOS and study its correlation with the various metabolic, clinical, and hormonal parameters.Materials and Methods:A cross-sectional study involving 69 PCOS women was carried out in a tertiary care center hospital. The diagnosis of PCOS was made according to the Rotterdam criteria. Blood samples were collected in the follicular phase of the menstrual cycle and analyzed for fasting luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17-hydroxyprogesterone (17-OHP), total testosterone (T), glucose, insulin, and lipid profile. Urinary albumin was measured in the first void spot urine sample.Results:The mean age of the subjects was 22.0 ± 4.1 years and 21.8 ± 4.7 years in normoalbuminuric and microalbuminuric groups, respectively. Urinary albumin excretion (UAE) varied from 5 mg/l to 100 mg/ml, with a median of 5 mg/l. Microalbuminuria was observed in 17/69 (24.6%) of subjects. The mean UAE was 3.65 ± 4.44 mg/l in the normoalbuminuria group versus 45.29 ± 22.74 mg/l in the microalbuminuria group. Upon univariate analysis, hip circumference, diastolic blood pressure, and fasting blood glucose showed significant correlations with urinary albumin concentration (r = 0.264, 0.264, and 0.551, respectively; P = 0.028, 0.029, and 0.000, respectively). No association between UAE and the usual cardiovascular risk factors could be found upon regression analysis.Conclusion:About 24.6% of women with PCOS showed presence of microalbuminuria in the first void spot urine sample. Screening for the presence of microalbuminuria can help in early identification of a subset of PCOS women with a high risk for future CVD, who can be subjected to preventive strategies at the earliest. However, further studies are needed before recommending routine use of UAE in PCOS cases for the detection of CVD risk.

The association of albuminuria, arterial stiffness, and blood pressure status in nondiabetic, nonhypertensive individuals

Although several studies have reported an association between microalbuminuria and pulse wave velocity in patients with hypertension or diabetes, there have been no reports of their significance in apparently healthy individuals. Microalbuminuria and brachial-ankle PWV (baPWV) were investigated in a sample of 3826 nonhypertensive, nondiabetic individuals (3598 men, mean age 50 ± 11.3 years) at Kangbuk Samsung Health Promotion Center between 2006 and 2009. The patients were classified into two groups according to urinary albumin-creatinine ratio (UACR) in morning urine specimens: normoalbuminuria (<30 μg/mg) and microalbuminuria (30-300 μg/mg). The prevalence of prehypertension (preHT) and microalbuminuria was 52.5 and 4%, respectively. Abnormal baPWV and microalbuminuria each has unfavorable cardiometabolic profile. The absolute values of baPWV were correlated with those of UACR (r = 0.220, P < 0.001). In multivariate regression analysis, the microalbuminuria group showed an independent association of increasing baPWVs irrespective of potential confounders, compared with the normoalbuminuria group (standard β = 0.049, P < 0.001). In the subspecified analyses, category III (preHT + normoalbuminuria) and IV (preHT + microalbuminuria) had higher odds ratio (ORs) [95% confidence interval (CI)] for the abnormal baPWV group, compared with category I (normal BP + normoalbuminuria) [2.345 (2.010-2.735) and 3.822 (2.367-6.171), respectively]. These findings demonstrate epidemiologic evidence for an independent association between arterial stiffness and microalbuminuria, indices of subclinical target organ damage in nonhypertensive, nondiabetic individuals, which suggests the possibility of a similar pathophysiologic mechanism involved in these two indices of subclinical target organ damage.

J-028 PULSE PRESSURE AS A RISK FACTOR FOR THE INCIDENCE OF MICROALBUMINURIA IN THE GENERAL POPULATION

Background Microalbuminuria (MA) is associated with vascular endothelial dysfunction and is known to be an independent risk factor for cardiovascular diseases even in non-diabetic, non-hypertensive general population. Previous cross-sectional studies have shown that the pulsatile component of blood pressure is related to the prevalence of MA, however, the association between baseline pulse pressure (PP) and the future onset of MA has not been clarified. Methods Study subjects were 2253 inhabitants of the town of Watari who had regular medical check-ups both in 2008 and 2009. Demographic data, fasting blood samples for lipid and glucose metabolism, sitting blood pressures, and urinary albumin-creatinine ratio (UACR) in a spot urine sample were obtained. Of these, subjects with nonfasting blood sampling and missing data components were excluded. We also excluded subjects under treatment with antihypertensive and/or antidiabetic drugs. Finally, we excluded subjects with baseline MA (UACR of 30–299 mg/gCr) and overt albuminuria (UACR>300 mg/gCr), leaving 1462 subjects for the statistical analysis. Results Among 1462 subjects with baseline normoalbuminuria (NA), 44 developed MA at one year follow-up (incident MA group). The incident MA group exhibited higher waist circumference (88.0 ± 8.65 vs. 84.3 ± 8.65 cm, p < 0.01), body-mass index (24.1 ± 2.98 vs. 22.7 ± 3.0 kg/m2, p < 0.01), systolic/diastolic blood pressures (135.3 ± 17.6/77.1 ± 11.0 vs. 124.3 ± 17.7/71.9 ± 11.0 mmHg, p < 0.01 for both), PP (58.2 ± 11.1 vs. 52.5 ± 11.1 mmHg, p < 0.01), and increased triglyceride (median 96.5 mg/dL vs. 87.0 mg/dL, p < 0.05), compared with the NA group. Multivariate logistic regression analysis revealed that the higher baseline PP (PP≥60mmHg) was associated with increased risk for the one-year incidence of MA (odds ratio: 2.49, 95%CI: 1.16–5.60), with the lower baseline PP (PP < 50mmHg) as reference. Conclusions Higher pulse pressure is a risk factor for the incidence of MA in the general population, implying that the pulsatile component of blood pressure is a contributing factor to the development of MA.

Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study

The purpose of this study was to investigate the prevalence of tubular damage in short-term (less than five years) type 2 diabetes mellitus (T2DM) patients and to explore the correlation between tubular markers and their relationship with renal indices at different stages of diabetic nephropathy. A group of 101 short-term T2DM patients and 28 control subjects were recruited. Tubular markers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D: -glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1), as well as urinary albumin excretion were measured in voided urine. Glomerular filtration rate (GFR) was estimated via Macisaac's formula. The patients were further categorized into three groups, namely, the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, according to their urine albumin/creatinine ratio (UACR). Urinary tubular markers were compared and their correlations with renal indices [UACR and estimated GFR (eGFR)] were analyzed among the different diabetic groups. Compared with the control group, Urinary NGAL [median (IQR)][83.6(41.4-138.7) μg/gcr vs. 32.9(26.1-64.5) μg/gcr], NAG [13.5(8.7-17.9) U/gcr vs. 7.6(6.5-13.0) U/gcr] and KIM-1 [120.0(98.4-139.9) ng/gcr vs. 103.1(86.8-106.2) ng/gcr] in the T2DM were all markedly increased. For all patients, urinary NGAL had stronger positive correlations with UACR than NAG (R = 0.556 vs. 0.305, both P < 0.05). In addition, only urinary NGAL showed a negative correlation with eGFR (R = -0.215, P < 0.05). Urinary KIM-1, however, showed no significant difference among the three T2DM groups and did not correlate with either UACR or eGFR. As UACR increased from the normoalbuminuria to the last macroalbuminuria group, all of the markers increased. However, only the concentrations of NGAL were statistically different among the three diabetic groups. The correlation between the tubular markers and their relationships with the renal indices differed markedly among the three T2DM groups. In conclusion, these results suggest that tubular damage is common in short-term T2DM patients. Urinary NGAL may be a promising early marker for monitoring renal impairment in short-term T2DM patients.

Urinary Podocyte-Associated mRNA profile in Various Stages of Diabetic Nephropathy

BackgroundPodocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.MethodsDN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.ResultsThe urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = −0.349, p = 0.01).ConclusionThe urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus

Observations on the association between the vascular endothelial growth factor (VEGF) gene polymorphism and nephropathy have been inconsistent, which might be due to ethnic and geographical variations. Furthermore, the relationship between +405 G/C polymorphism and albuminuria in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between +405 G/C polymorphism and albuminuria in an population from Tehran of Iran. A total of 255 consecutive patients with type 2 diabetes and microalbuminuria (Group A) and 235 patients with type 2 diabetes and normoalbuminuria (Group B) were included. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect the VEGF alleles. In univariate analysis, the groups were statistically similar in all variables except for HbA1c (8.53 ± 1.7 in Group A vs. 8.2 ± 1.73 in Group B; P = 0.034), 24-h urinary albumin (201.33 ± 84.8 in Group A vs. 22.88 ± 3.5 in Group B; P < 0.001), and the frequency of GG genotype (31% in Group A vs. 18.7% in Group B; P = 0.006). The GG genotype was the independent predictor of albuminuria [P = 0.014, OR = 1.771, 95% confidence interval (CI) = 1.124-2.790]. Our study showed that the G allele was not associated with albuminuria, but the GG genotype in the VEGF gene is independently associated with development of nephropathy in the our diabetic population.

41 Poor Glycemic Control but not Dyslipidemia is Associated with Albuminuria in Patients with Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM): A Kidney Early Evaluation Program (KEEP) Report

POOR GLYCEMIC CONTROL BUT NOT DYSLIPIDEMIA IS ASSOCIATED WITH ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) AND TYPE 2 DIABETES MELLITUS (T2DM): A KIDNEY EARLY EVALUATION PROGRAM (KEEP) REPORT Subhasish Bose, Nehal N. Mehta, Shu-Cheng Chen, Suying Li, Peter A. McCullough. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota; St. John Providence Health System, Providence Park Heart Institute, Novi, Michigan. Dyslipidemia and albuminuria have both been associated with unfavorable cardiovascular prognosis in patients with T2DM. However, the direct relation between lipid abnormalities and overall glycemic control with urinary albumin-creatinine ratio (ACR) in CKD patients with T2DM has not been elucidated. We sought to investigate the association of dyslipidemia and glycemic control with albuminuria in KEEP participants with T2DM and CKD stage ≤3. Our study included a total of 6639 eligible KEEP patients from June ‘08 to December ‘09 with glycosylated hemoglobin (HbA1c) values. After excluding nondiabetic, non-CKD and patients with missing values of urinary ACR, the total sample size was 2141. Baseline characteristics and health screening results based on quartiles of HbA1c were compared. We performed multivariate logistic regressions in estimating individual association of lipid parameters (per 10 mg/dl change in serum level) and HbA1c values with ACR, adjusting for age, gender and race. These associations were compared across different degrees of ACR groups: normo-albuminuria ( 300 mg/g). Association between components of serum lipid profile with ACR was not significant. HbA1c was associated with ACR when compared between normo-albuminuria and micro-albuminuria groups [OR=1.32, (95% CI: 1.23-1.41), p<0.001]. Association was attenuated in the micro-albuminuria versus macroalbuminuria groups [OR=1.15, (95% CI: 1.05-1.27), p<0.01]. In this cross-sectional study of 2141 KEEP participants with T2DM and CKD, overall glycemic control measured by HbA1C but not dyslipidemia was associated with urinary ACR.

Relationship Between Microalbuminuria and Vulnerable Plaque Components in Patients With Acute Coronary Syndrome and With Diabetes Mellitus - Virtual Histology-Intravascular Ultrasound -

The purpose of the present study was to use virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between microalbuminuria and plaque components in 920 patients. Patients with albumin levels <30mg/g creatinine were defined as having normoalbuminuria (n=824), and those with albumin levels 30-300mg/g as having microalbuminuria (n=96). The microalbuminuria group contained more patients with acute coronary syndrome (ACS; 72% vs. 61%, P=0.018) and more patients with diabetes (53% vs. 26%, P<0.001). In ACS patients, %necrotic core (NC) volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (19±10% vs. 15±9%, P=0.019), but not in patients with stable angina. In ACS patients, thin-cap fibroatheroma (TCFA) was observed more frequently in the microalbuminuria group (36% vs. 18%, P=0.008), and microalbuminuria was the independent predictor of TCFA (odds ratio [OR], 1.106; 95% confidence interval [CI]: 1.025-1.144, P=0.018). In diabetic patients, %NC volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (20±9% vs. 16±10%, P=0.017), but not in non-diabetic patients. In diabetic patients, TCFA was observed more frequently in the microalbuminuria group (38% vs. 17%, P=0.002) and microalbuminuria was the independent predictor of TCFA (OR, 1.120; 95%CI: 1.038-1.204, P=0.012). Microalbuminuria was associated with a higher number of vulnerable plaque components in ACS and diabetic patients. More intensive medical therapy is needed to stabilize the vulnerable plaque if microalbuminuria is observed in diabetic ACS patients.