Urine Albumin-creatinine Ratio Levels Research Articles

Dapagliflozin treatment of patients with chronic kidney disease without diabetes across different albuminuria levels (OPTIMISE-CKD)

Abstract Background We compared kidney and cardiorenal protection in patients without type 2 diabetes across urine albumin-creatinine ratio (UACR) levels after initiation on dapagliflozin for the treatment of chronic kidney disease (CKD). Methods OPTIMISE-CKD is an observational study describing dapagliflozin treatment for CKD. Adult patients with CKD without type 2 diabetes were included in the primary analysis. Baseline UACR was grouped as normal/mildly elevated (0–29 mg/g), low (30–200 mg/g) and high (>200 mg/g). Outcomes were estimated glomerular filtration rate (eGFR) trajectories/slopes, cardiorenal complications and all-cause mortality. Results In total, 1480 patients had low (n = 796) and high (n = 684) UACR. The two groups were similar at baseline, aged 75 and 74 years, and 42% and 39% female, respectively. After dapagliflozin initiation, an acute eGFR dip of 3 mL/min/1.73 m2 was observed, followed by a flat development in both groups. The eGFR slope (95% confidence interval [CI]) for patients with low UACR was 0.79 mL/min/1.73m2 per year (–0.59, 2.56), and similar to patients with high UACR (0.40 mL/min/1.73m2 per year [–0.46, 1.38]). Risks of cardiorenal complications and all-cause mortality were similar, with adjusted hazard ratios of 0.89 [95% CI 0.66, 1.19] and 1.10 [95% CI 0.63, 1.92], respectively. Analogous results were found in those with normal/mildly elevated UACR. Conclusions Dapagliflozin in patients without type 2 diabetes for the treatment of CKD demonstrated similar kidney protection, cardiorenal and all-cause mortality risk across UACR levels. This suggests that the efficacy of dapagliflozin found in clinical trials expands to real-world patients with CKD, regardless of albuminuria levels.

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). Multicenter prospective cohort study. 7 U.S. clinical centers. 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. UACR was measured once. Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. None.

Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.

Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury. We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib. Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment. Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.

Correlation of HbA1c and Insulin Resistance with Urine Albumin Excretion in Non Diabetic Obese Population: A Cross-sectional Study

Introduction: A number of metabolic disorders are linked to obesity, which is a global health concern. Although renal impairment is a serious side-effect of obesity, its connection to insulin resistance is still a subject of discussion. Aim: To assess the correlation between microalbuminuria and HbA1c levels, as well as the association between Insulin Resistance (IR) and renal function in obese individuals. Materials and Methods: The present study was a crosssectional study conducted in patients attending the obesity clinic, in Endocrinology department, of a tertiary hospital in Kerala, India. A total of 144 obese individuals participated, meeting age, Body Mass Index (BMI), and health-related. Insulin resistance was measured using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while renal function was measured using the Urine Albumin Creatinine Ratio (UACR). Correlation analysis was conducted to investigate relationships between variables. Results: The study found a weak association between UACR and HbA1c levels and insulin resistance (r-value=0.159, p-value=0.056). Subjects with insulin resistance had significantly higher levels of microalbuminuria. Despite these connections, the mean UACR levels remained within the typical reference range. Conclusion: This study emphasises the importance of early renal health screening in obese individuals, with HbA1c and microalbuminuria measurements as promising methods for preventing kidney impairment. To establish causation in the complex interplay between metabolic variables and renal function in obesity and insulin resistance, future research should focus on understanding the underlying mechanisms and conducting longitudinal examinations.

PS-C28-2: STROKE RISK OF THE ELDERLY PATIENTS WITH NOCTURNAL HYPERTENSION DEFINED USING HOME BLOOD PRESSURE MONITORING IN JAPANESE GENERAL PRACTICE POPULATION

Objective: To investigate the association between nocturnal hypertension defined using home blood pressure (BP) monitoring (HBPM) and the prevalence, extent of cardiovascular target organ damage (TOD), and cardiovascular disease (CVD) event risks in participants with ≧ 65 years in general clinical practice. Design and method: We used the dataset of the Japan Morning Surge-Home BP (J-HOP) Study that recruited 4,310 participants with cardiovascular risk factors. Among them, we assessed the participants with ≧ 65 years who measured nocturnal home BP (n = 1,349, mean age 72.0 year, 48.6% men). We define nocturnal hypertension as nocturnal systolic (SBP) ≧ 120 mmHg or diastolic (DBP) ≧ 70 mmHg, using HBPM. Nocturnal home BP was automatically measured at least 1 day within the 14 days (2 AM, 3 AM, and 4 AM). We use the average of all nocturnal home BP values. N-terminal pro-brain natriuretic peptide (NT-proBNP) and urine albumin: creatinine ratio (UACR) were used as surrogate markers of TOD. The CVD outcomes were incident stroke and coronary heart disease (CHD) events. Results: The prevalence of nocturnal hypertension defined by HBPM was 61.7% of all study participants with ≧ 65 years. The participants with nocturnal hypertension defined by HBPM presented higher levels of log-transformed NT-proBNP and UACR at baseline compared to those with controlled nocturnal BP group. Over a median 4.0-year follow-up (5,453 person-years), 36 stroke events and 31 CHD events occurred, respectively. The nocturnal hypertension group had a higher incidence rate of stroke events compared with the controlled BP group. Concerning CHD, the incidence rate of CHD was similar between two groups (Figure). Cox model results suggested that the participants with nocturnal hypertension had a higher risk of stroke compared to those with controlled nocturnal BP group after adjustments for log-transformed NT-proBNP and UACR levels (adjusted hazard ratio 3.42; 95% confidence interval 1.15–10.19). Conclusions: In this Japanese population with ≧ 65 years, the participants with nocturnal hypertension defined by HBPM was significantly associated with stroke risk, independently of the extent of TOD.

The urine albumin creatinine ratio is one of the predictors of acute kidney injury in hepatitis C-related cirrhotic hepatic encephalopathy

Background/objectiveHepatic encephalopathy (HE) is a main manifestation of acute decompensation in liver cirrhosis. Recently, systemic inflammation was proposed as a key mechanism in the development of acute kidney injury (AKI) in cirrhotic patients. The urine albumin creatinine ratio (UACR) is considered a marker of systemic inflammation in a variety of clinical settings. Here, we aimed to evaluate the role of the urine albumin creatinine ratio in the early prediction of AKI in HE.Patients and methodsSixty-seven consecutive patients presented with cirrhotic HE, and 59 age- and sex-matched cirrhotic patients with no history of HE served as controls. HE was defined and graded by the West Haven criteria. The severity of liver cirrhosis was evaluated by the Child-Turcotte-Pugh (CTP) score, and model for end-stage liver disease (MELD) score. The incidence of AKI that developed during hospital admission and the in-hospital mortality rate was estimated among HE patients. In addition, predictors of AKI were analyzed.ResultsThe mean age of HE patients was 58.09±12.26 years; 36 (53.7%) were males, and 31 (46.3%) were females. Among HE patients, 16 (23.9%) developed AKI during hospital admission. The in-hospital mortality rate among HE patients was 22 (32.8%), the in-hospital mortality among HE-AKI patients was 81.3% (n=13/16), and UACR levels > 91.5 mg/g identified HE-AKI with 81.25% sensitivity (AUC = 0.85, P ≤ 0.001).ConclusionsPatients with cirrhotic HE are at high risk of AKI. HE-AKI patients had a high rate of in-hospital mortality. Estimation of UACR at hospital admission is suggested for the early detection of patients with HE-AKI.

Urine Albumin-Creatinine ratio is associated with prognosis in patients with diabetic foot osteomyelitis

AimsWe aimed to explore the association between albuminuria and clinical outcomes in patients with diabetic foot osteomyelitis (DFO). MethodsThis is an observational retrospective study and a total of 202 inpatients with DFO were eligible for inclusion in our study. Based on urine albumin-creatinine ratio (UACR), the patients were divided into three groups: normoalbuminuria group, microalbuminuria group and macroalbuminuria group. The data collected include demographics data, laboratory data, clinical diagnostic data, diabetic foot examination and clinical visit data. The association was then evaluated between albuminuria and all-cause mortality, major cardiovascular adverse events (MACE) and mixed endpoint events. ResultsThe mean age was 60.3 years, 62.9% were male and 45.05% were urinary protein-positive. The incidence rates of all-cause mortality, MACE and mixed endpoint events related to elevated UACR were significantly increased in patients with DFO (all P for trend < 0.01). After adjusting for confounders, compared with normoalbuminuria group, the risk of all-cause mortality, MACE and mixed endpoint events in the microalbuminuria group increased by 81.8%, 135.4% and 136.4%, respectively. The risk of all-cause mortality, MACE and mixed endpoint events in the macroalbuminuria group increased by 246.2%, 145.1% and 252.3%, respectively. The population attributable risk percentage (PAR%) suggested that 50.16% of all-cause mortality, 47.85% of MACE and 59.11% of mixed endpoint events could be attributed to the elevated UACR. Meanwhile, compared with normoalbuminuria, those with microalbuminuria or macroalbuminuria have lower apoA1 and ABI, higher SCr and higher incidence rate of CHD, hindfoot infection and severe infection (all P < 0.05). ConclusionsIn patients with DFO, the UACR level is associated with all-cause mortality, MACE and mixed endpoint events and elevated UACR levels increase the risk of all-cause mortality, MACE and mixed endpoint events.

Relationship between Vitamin D Deficiency, Albuminuria, Peripheral Artery Disease and 5-year Mortality in Chronic Kidney Disease.

To investigate the effects of vitamin D deficiency, albuminuria and peripheral artery disease (PAD) relationships, on 5-year mortality in patients with chronic kidney disease (CKD) . Observational study. Department of Internal Medicine, Kartal Dr Lutfi Kırdar City Hospital, İstanbul, Turkey, from August 2015 to August 2020. The study included patients with stage 2-4 CKD, who were not previously diagnosed with peripheral artery disease (PAD) and were not on hemodialysis. Each patient's ankle-brachial index (ABI) was measured at rest with a portable vascular hand doppler; and an ABI of <0.9 was considered to be PAD. The mortality status of the participants were confirmed by the national death reporting system. A total of 110 CKD patients, mean age of 62.1±9.7 years, 36.4% women, were included in the study. It was found that 17.3% of the patients had vitamin D deficiency, 15.4% had vitamin D insufficiency, 32.7% had asymptomatic PAD, 33.9% had microalbuminuria and 39.4% had macroalbuminuria. It was observed that as vitamin D levels decreased, the frequency of albuminuria, and the prevalence of PAD, was on an increasing trend. A significant correlation was found between 5-year mortality, gender, body mass index (BMI), glomerular filtration rate (eGFR), urine albumin creatinine ratio (UACR), hemoglobin A1c (A1c), calcium (Ca), phosphate (P), vitamin D, ankle brachial index (ABI), and the neutrophil lymphocyte ratio (NLR) as a result of univariate cox-regressionanalysis. In the multivariate cox-regression model, it was observed that vitamin D, ABI and UACR levels continued being significant, independent of age, gender, BMI and eGFR levels. Conclusion: Vitamin D deficiency, PAD and albuminuria, which are separate predictors of mortality, were shown to be independent predictors of long-term mortality in CKD patients. Key Words: Chronic kidney disease, Mortality, Peripheral arterial disease, Vitamin D deficiency, Albuminuria, Ankle-brachial index.

Microalbuminuria and Serum Cystatin C Correlation as Early Markers of Kidney Dysfunction in Patients with Type 1 Diabetes Mellitus

Introduction: Diabetes mellitus is the most common single cause of End Stage Renal Disease (ESRD). About 20-30% of patients with Type 1 Diabetes Mellitus (Type 1 DM) develop diabetic nephropathy as a serious complication which is the major cause of morbidity and mortality. Early identification of renal impairment is crucial to prevent the progression of nephropathy to a significant degree, because several interventions have greatest impact if initiated very early in the course of the disease. Aim: To study the correlation of microalbuminuria and serum cystatin C for the early prediction of renal impairment in patients with Type 1 DM. Materials and Methods: This was a cross-sectional study conducted from January 2016 to June 2016 on type 1 DM patients attending Diabetology Outpatient Department (OPD). According to the duration of diabetes, pateints were divided into two groups, Group I with &lt;5 years and Group II with &gt;5 years duration. The patients in each group were categorised as cases and controls, based on the Albumin Creatinine Ratio (ACR), serum urea, creatinine, cystatin C, glycated haemoglobin (HbA1c), and urine ACR levels were estimated. Student’s unpaired t-test was used to compare the means between two independent groups. Pearson correlation coefficient was used to estimate the degree of correlation between two quantitative variables. Results: Seventy-two patients with type 1 DM were included in the study. Cystatin C levels in cases (0.89±0.35) when compared to controls (0.67±0.26) in more than five years duration of type 1 DM was found to be statistically significant (p&lt;0.01). Positive correlation between cystatin C and ACR (r=0.4, p&lt;0.05) was found to be statistically significant in more than five years duration. It indicates that serum cystatin C levels increases as the values of ACR increases. There was no significant difference in cystatin C levels in patients with less than five years duration of type 1 DM. Conclusion: Serum cystatin C may be considered as an early predictor of renal impairment in type 1 DM patients with more than five years duration. However, in this study cystatin C carries no significance in less than five years duration of type 1 DM patients.

Urine Haptoglobin/Creatinine Ratio Correlates with Tubular Injury Biomarkers and Severity of Albuminuria in Type 2 Diabetes Patients.

This aim of this study was to investigate the correlation between urine haptoglobin/creatinine ratio(UHCR) and tubular injury biomarkers or severity of albuminuria in type 2 diabetes. Recruited T2DM patients (n=120) were divided into three groups based on urine albumin/creatinine ratio (UACR): normal albuminuria (Normo group, UACR<30 mg/g, n=40), microalbuminuria (Micro group, 30 mg/g ≤UACR<300 mg/g, n=38), and macroalbuminuria (Macro group, UACR ≥300 mg/g, n=42), with matched healthy individuals (NC group, n=30) as controls. ELISA assay was used to detect the levels of urine haptoglobin, NGAL and KIM-1. Automated biochemical analyzer was applied to detect the concentrations of urine creatinine and retinol binding protein (RBP). To eliminate concentration errors, urine NGAL, KIM-1, and RBP were normalized by creatinine and expressed as UHCR, UNCR, UKCR, and URCR, respectively. We found UHCR was significantly increased in T2DM patients as compared with NC group. Among the three diabetic groups, the Macro group had the highest level of UHCR, whereas the Normo group had the lowest level. T2DM patients with higher UHCR levels also had higher levels of UNCR, UKCR, and URCR. Spearman's correlation analysis indicated that UHCR was positively correlated with UACR, UNCR, UKCR, or URCR levels, and negatively correlated with eGFR. ROC curve analysis showed that UHCR was a sensitive and specific indicator for early diagnosis of DN. Stepwise multiple regression analysis showed that UHCR and UNCR were independent variables for UACR. Our research demonstrated that UHCR correlates with tubular injury biomarkers, including UNCR, UKCR, and URCR, and is independently associated with the severity of albuminuria in T2DM.

Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

This study summarizes the evidence from randomized controlled trials (RCTs) to assess the effects of SGLT2 inhibitors on renal function and albuminuria in patients with type 2 diabetes. We searched PubMed, Web of Science, Cochrane Library and EMBASE for reports published up to March 2018 and included RCTs reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (UACR) changes. Data extraction and assessment of research quality based on Cochrane risk biasing tools. Data were calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95% confidence intervals (CIs) were pooled using a random effects model. Fifty-one studies were included that evaluated eGFR levels, and 17 studies were included that evaluated UACR levels. A meta-analysis showed that SGLT2 inhibitors had no significant effect on eGFR levels (SMD - 0.02, 95% CI - 0.06, 0.03, p = 0.45), and eGFR reduction was observed in the subsets of the duration of the trial 12 < duration ≤ 26 weeks (SMD - 0.08, 95% CI - 0.13, - 0.02, p = 0.005) and mean baseline eGFR < 60ml/min per 1.73 square meters (SMD - 0.22, 95% CI - 0.37, - 0.07, p = 0.004). We found that SGLT2 inhibitors reduced UACR levels in patients with type 2 diabetes (SMD - 0.11, 95% CI - 0.17, - 0.05, p = 0.0001). Compared with monotherapy, the combination with other hypoglycemic agents can reduce albuminuria levels (SMD - 0.13, 95% CI - 0.19, - 0.06, p < 0.0001). The effect of SGLT2 inhibitor on eGFR in patients with T2DM was not statistically significant, but it was effective in reducing albuminuria levels.

Cyclophilin A and CD147 associate with progression of diabetic nephropathy

To find the associations of circulating cyclophilin A (CyP A) and CD147/EMMPRIN with renal outcomes in type 2 diabetes patients and possible pathogenesis involved. Total 131 patients were recruited since 2004. Glycated hemoglobin, blood glucose and urine albumin–creatinine ratio levels at baseline and every 3 months were measured. Plasma CyP A and CD147 were also measured at baseline. Patients were divided into two groups based upon the median level of the baseline plasma CyP A value: < 93.64 ng/mL (group A, n = 65), ≥ 93.64 ng/mL (group B, n = 66). The estimated glomerular filtration rate was calculated at each follow-up visit. Besides, mitochondrial function assay by cellular mitochondrial energy utility was studied when cells were exposed to glucose or exogenous CyP A or both. Multivariate analysis, using median level (93.64) ng/mL as the cut-off value, revealed that circulating CyP A and CD147 levels at baseline were associated with the baseline estimated glomerular filtration rate (eGFR) (p = .042 and p = .001 separately) in cross-sectional analysis. Longitudinally, higher baseline plasma CyP A level was also correlated to a rapid decline in eGFR (p = .016). The results were also significant when using the continuous plasma CyP A level (p = .003). In cells exposed to glucose, results of oxygen consumption rate (OCR) showed a significant reduction in basal respiration, maximal respiration and ATP production. Depressed OCR further occurred when incubated with both of CyP A and glucose. Plasma CyP A and CD147 can serve as indicators of renal disease progression in type 2 diabetes patients.

Urinary albumin excretion, HMW adiponectin, and insulin sensitivity in type 2 diabetic patients undergoing bariatric surgery.

Microalbuminuria portends an increased risk for renal and cardiovascular diseases in diabetes. In this pilot study, we determined the effect of weight loss induced by different types of bariatric surgery on albuminuria in severely obese type 2 diabetic (T2DM) subjects. Fifteen consecutive T2DM patients (9M/6F, 51+/-14 years, body mass index (BMI) 49+/-9 kg/m2, HbA1c 7.2+/-1.1 percent) undergoing either Roux-en-Y gastric bypass (RYGB; N=9) or other types of bariatric surgery (N=6) underwent determination of urine albumin/creatinine ratio (UACR) and adipokine and insulin sensitivity during a mixed meal tolerance test performed 2 weeks prior to and 6 months following surgery. Following RYGB, there was a significant decrease in BMI ((-4.74)+/-(-5.05) kg/m2), fasting glucose, cholesterol, and leptin levels. Insulin sensitivity (Matsuda index [12.05+/-3.81, p=0.003]) and high molecular weight (HMW) adiponectin increased significantly along with a significant reduction in UACR (median, 36 mg/g [7-94] vs. 27 mg/g [5.5-42.5], p=0.01). The reduction in UACR following RYGB was inversely correlated with the Matsuda index (r=-0.74), p=0.02) and HMW adiponectin (r=(-0.67), p=0.04). In contrast, despite reduction in BMI ((-4.11)+/-(-4.10) kg/m2) following other types of bariatric surgery (n=6), there was no significant improvement in insulin sensitivity (0.88+/-2.40, p=0.63), UACR, or HMW adiponectin levels. RYGB in severely obese DM subjects is associated with a reduction in albuminuria that correlates to the improvement in insulin sensitivity and HMW adiponectin. The data point to a need for larger studies to confirm these findings and evaluate the micro-macrovascular benefits including renal parenchymal benefits of different types of bariatric surgery in T2DM.

Relationship between antinuclear antibody and microalbuminuria in the general population: the Takahata study

Microalbuminuria, a marker of vascular damage, is associated with increased risk of progressive renal deterioration, cardiovascular disease and mortality. However, the relationship between antinuclear antibody (ANA) and microalbuminuria in the general population is unknown. Thus, we conducted a cross-sectional study to examine the relationship between ANA and microalbuminuria. The subjects of this community-based study were individuals over 40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) was calculated from a single-spot urine specimen collected in the morning. ANA was examined by enzyme immunoassay (EIA). Among the 2,875 subjects (mean age 63 years; men 1,276; women 1,599), positive ANA (ANA index >or=20.0) was detected in 16.9% of the total population (men 12.9%, women 20.3%) and the prevalence of positive ANA increased with age. The prevalence of microalbuminuria (UACR 30-300 mg/g), but not macroalbuminuria (UACR > 300 mg/g), was significantly higher in the positive ANA group than the negative ANA group (24.1% vs. 16.0%, respectively, P < 0.001). Along with the increase of the ANA index, the prevalence of microalbuminuria and UACR levels were increased. Multivariate logistic regression analyses showed that ANA was significantly associated with microalbuminuria (odds ratio [OR] 1.63 and 95% confidence interval [95%CI] 1.27-2.10). These associations were significant in women, but not men, when examined separately. These results indicate that the presence of ANA is associated with microalbuminuria in the general population, especially women.

Clinical utility of trace proteinuria for microalbuminuria screening in the general population

The urine dipstick test that regards > 1+ proteinuria as positive is unsuitable for microalbuminuria screening owing to its low sensitivity in the general population. We conducted a cross-sectional survey to examine whether trace proteinuria could be an indicator of microalbuminuria. The subjects were 2321 participants in a community-based health check-up in Takahata, Japan. Dipstick tests for proteinuria and the urine albumin-creatinine ratio (UACR) measurement were performed with single-spot urine specimens collected early in the morning. The results of the dipstick tests were recorded as (-), trace, (1+), (2+), and (3+). Micro- and macroalbuminuria were defined as UACR 30-300 mg/g and > 300 mg/g, respectively. Overall, the prevalence and median UACR levels of urine protein (-), trace, (1+), (2+), and (3+) were 92.0% (8.8 mg/g), 3.5% (43 mg/g), 2.6% (81 mg/g), 1.4% (315 mg/g), and 0.5% (1073 mg/g), respectively. Within the trace proteinuria category, the prevalence of microalbuminuria in all subjects, men, subjects >or=60 years, diabetic subjects, and hypertensive subjects was 59.3%, 73.8%, 71.2%, 88.9%, and 68.0%, respectively. By regarding trace proteinuria as positive, the sensitivity of the urine protein dipstick test for micro- and macroalbuminuria was improved (from 23.3% to 37.1%), while its specificity was not significantly changed (from 98.9% to 97.3%). Trace proteinuria could be a useful indicator of microalbuminuria in the general population, and especially in subjects at high risk of cardiovascular disease.

Heritability of GFR and albuminuria in Caucasians with type 2 diabetes mellitus

Background: Elevated urinary albumin excretion and decreased glomerular filtration rate (GFR) are risk factors for cardiovascular death and end-stage renal disease in individuals with type 2 diabetes mellitus (DM). Methods: To determine the extent of familial aggregation of GFR and urine albumin-creatinine ratio (ACR), we calculated heritability (h2) estimates by using a variance component approach. Results: Among 662 participants with DM from 310 families (422 DM-concordant sibling pairs), 51.8% (n = 343) were women, mean age was 62.3 ± 9.2 (SD) years (median, 62.6 years), diabetes duration was 10.8 ± 7.6 years (median, 9 years), GFR was 67.6 ± 19.0 mL/min (median, 64.7 mL/min), and urine ACR was 139.7 ± 631.4 mg/g (median, 13.1 mg/g). Estimated h2 of GFR was 0.75 ± 0.10 (P < 0.0001) after adjusting for age, sex, mean arterial blood pressure, medications, and hemoglobin A1c level. These covariates accounted for only 2% of the total phenotypic variation in log GFR. Similarly, estimated h2 of ACR was 0.46 ± 0.12 (P < 0.0001) when adjusting for these covariates, with covariates contributing only 9% of phenotypic variation. Conclusion: These data provide strong evidence that among Caucasians with type 2 diabetes, GFR and urine ACR show strong familiality, suggesting that genetic factors exhibit significant influences. Given their biological and clinical importance and the similarity of these estimates with other cardiovascular disease- and DM-related traits, efforts to map genes that influence GFR and urine ACR levels should have increased importance.

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study.

Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.