Urinary Albumin Excretion Values Research Articles

Cardio Vascular Autonnomic Dysfunction in Type 2 Diabetes Patients with Microalbuminuria

Objective: Main objective of this study is to determine the prevalence of cardiovascular autonomic dysfunction in type-2 diabetes patients with microalbuminuria. Study Design: Descriptive/ observational study Place and Duration: Department of Cardiology, DHQ Hospital Alpurai, Shangla, from December, 2021 to May, 2022. Methods: Total 70 patients of both genders diagnosed diabetes 2 mellitus were presented in this study. Patients were aged between 20-80 years. Patients details demographics were recorded after taking written consent. Prevalence of cardiovascular autonomic dysfunction with microalbuminuria was assessed by statistical analysis. Microalbuminuria was diagnosed among patients if urinary albumin excretion was >30-300mg/g and graded into mild, moderate and severe according to value of urinary albumin excretion was (20–50 mg/24 hr, 50–100 mg/24 hr, 100–300 mg/24 hr). Complete data was analyzed by SPSS 20.0 version. Results: Out of 70, 38 (54.3%) were males and 32 (45.7%) were females. Mean age of the patients were 49.71±17.8 years with mean BMI 28.41±9.42 kg/m2. Mean ACR of microalbuminuria was 166.7±47.8 mg/gm. Among 70 cases, mild microalbuminuria was found in 28 (40%) cases, moderate microalbuminuria was among 31 (44.3%) and 11 (15.7%) was severe microalbuminuria. Lethargy was the most common symptom found in 25 (35.7%) followed by anorexia 20 (28.6%). Frequency of Cardiac autonomic neuropathy was 58 (82.86%), Parasympathetic dysfunction found in 59 (84.3%) and sympathetic dysfunction was among 62 (88.6%). Conclusion: We concluded in this study that the cardiovascular autonomic dysfunction in type-2 diabetes patients highly associated with microalbuminuria with increased systolic diastolic pressure and heart rate. Keywords: Microalbuminuria, Type 2 Diabetes, Cardio autonomic dysfunction

Cardio Vascular Autonomic Dysfunction in Type 2 Diabetes Patients with Microalbuminuria

Objective: Main objective of this study is to determine the prevalence of cardiovascular autonomic dysfunction in type-2 diabetes patients with microalbuminuria. Study Design: Descriptive/ observational study Place and Duration: Study was conducted at Diabetes Hospital Hayatabad Peshawar and Mukhtar A Sheikh Hospital Multan for duration of six months from September, 2019 to February, 2020. Methods: Total 70 patients of both genders diagnosed diabetes 2 mellitus were presented in this study. Patients were aged between 20-80 years. Patients’ details demographics were recorded after taking written consent. Prevalence of cardiovascular autonomic dysfunction with microalbuminuria was assessed by statistical analysis. Microalbuminuria was diagnosed among patients if urinary albumin excretion was >30-300mg/g and graded into mild, moderate and severe according to value of urinary albumin excretion was (20–50 mg/24 hr, 50–100 mg/24 hr, 100–300 mg/24 hr). Complete data was analyzed by SPSS 20.0 version. Results: Out of 70, 38 (54.3%) were males and 32 (45.7%) were females. Mean age of the patients were 49.71±17.8 years with mean BMI 28.41±9.42 kg/m2. Mean ACR of microalbuminuria was 166.7±47.8 mg/gm. Among 70 cases, mild microalbuminuria was found in 28 (40%) cases, moderate microalbuminuria was among 31 (44.3%) and 11 (15.7%) was severe microalbuminuria. Lethargy was the most common symptom found in 25 (35.7%) followed by anorexia 20 (28.6%). Frequency of Cardiac autonomic neuropathy was 58 (82.86%), Parasympathetic dysfunction found in 59 (84.3%) and sympathetic dysfunction was among 62 (88.6%). Conclusion: We concluded in this study that the cardiovascular autonomic dysfunction in type-2 diabetes patients highly associated with microalbuminuria with increased systolic diastolic pressure and heart rate. Keywords: Microalbuminuria, Type 2 Diabetes, Cardio autonomic dysfunction

The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population

Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, using enzyme-linked immunosorbent assays. Associations with clinical variables and outcomes were analysed. Median DKK3 level was 32.8 ng/ml (28.0–39.0). In multivariable linear regression analysis, the strongest correlates for plasma DKK3 were age, body mass index and estimated glomerular filtration rate (eGFR). At baseline, 564 (6.7%) subjects had CVD (defined as a myocardial infarction and/or cerebrovascular accident) and 1361 (16.2%) subjects had CKD (defined as eGFR < 60 ml/min/1.73m2 and/or urinary albumin excretion (UAE) > 30 mg/24 h). Of subjects with known CVD and CKD follow-up status (respectively 7828 and 5548), 669 (8.5%) developed CVD and 951 (17.1%) developed CKD (median follow-up respectively 12.5 and 10.2 years). Crude logistic regression analysis revealed that DKK3 levels were associated with prevalent CVD (Odds ratio: 2.14 [1.76–2.61] per DKK3 doubling, P < 0.001) and CKD (Odds ratio: 1.84 [1.59–2.13] per DKK3 doubling, P < 0.001). In crude Cox proportional hazard regression analysis, higher DKK3 levels were associated with higher risk for new-onset CVD (Hazard ratio: 1.47 [1.13–1.91] per DKK3 doubling, P = 0.004) and CKD (Hazard ratio: 1.45, [1.25–1.69] per DKK3 doubling, P < 0.001). However, these associations remained no longer significant after correction for common clinical variables and risk factors, though independently predicted for new-onset CKD in a subgroup of subjects with the lowest UAE values. Together, DKK3 plasma levels are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD and only predicted for new-onset CKD in those subjects with the lowest UAE values.

Serum uric acid measurement and its correlation with urinary albumin-creatinine ratio in type-2 Diabetic subjects

Increased serum uric acid (SUA) is known to play a critical role in the development of type-2 diabetes mellitus (T2DM) as well as in progression of its complications. Hyperuricemia is an independent risk factor for kidney dysfunction in patients with diabetes. The appearance of albuminuria is the first sign of kidney damage and the mechanisms of hyperuricemia-induced renal injury mainly include oxidative stress, endothelial dysfunction, renal fibrosis, and inflammation. To determine the possible association of SUA with urinary albumin-creatinine ratio (ACR) in type-2 diabetic subjects, data with lab investigations of SUA and urinary ACR of 95 confirmed and known cases of T2DM were collected from the laboratory medicine department, DMWIMS Hospital, Wayanad Kerala. Based on the urinary albumin excretion values, diabetic subjects were divided into three groups (Normoalbuminuric, microalbuminuric &amp; macroalbuminuric groups). A significant increase in mean ACR from group-1--&gt;group-2--&gt;group- 3 was observed which is proportional to an increase in mean SUA levels suggesting that increase in SUA may be responsible for increased urinary albumin excretion. This study shows a positive correlation between SUA and ACR. Keywords: Serum uric acid; diabetes mellitus; hyperuricemia; kidney damage; T2DM; albuminuria; urinary albumin-creatinine ratio; diabetic nephropathy

Low circulating arachidonic acid is associated with macroalbuminuria in diabetic patients: a cross-sectional examination of the KAMOGAWA-DM cohort study

BackgroundDiabetic nephropathy, a major complication of diabetes, is the primary risk factor for dialysis, cardiovascular diseases, and mortality. Dietary fatty acids (FAs) have been revealed to be related with cardiovascular diseases in the general populations. The aim of this study was to investigate the association of circulating FAs with diabetic nephropathy.MethodsIn this cross-sectional study, 190 Japanese patients with type 2 diabetes were included. Circulating FAs were measured by gas chromatography-mass spectrometry. Spearman rank correlation coefficients were used to investigate the association between the logarithm of FAs and the logarithm of urinary albumin excretion (UAE). We have performed logistic regression analysis to determine the effect of FAs on the presence of macroalbuminuria, defined as UAE value ≥300 mg/g creatinine.ResultsMean age, body mass index, and duration of diabetes were 62.7 ± 12.1 years, 25.0 ± 4.5 kg/m2, and 9.8 ± 8.7 years, respectively. In total, 26 patients were diagnosed with macroalbuminuria. The logarithm of circulating arachidonic acid (AA) was negatively associated with the logarithm of UAE (r = − 0.221, p = 0.002). Additionally, circulating AA in patients with macroalbuminuria was lower than that in patients without macroalbuminuria (112.3 ± 75.3 mg/day vs. 164.8 ± 66.0 mg/day, p < 0.001). The logarithm of circulating AA was associated with the presence of macroalbuminuria after adjusting for covariates (odds ratio of Δ1 incremental: 0.32, 95% confidence interval: 0.10–0.99, p = 0.042).ConclusionsCirculating AA was negatively associated with UAE and the presence of macroalbuminuria.

Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

IntroductionNon-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people...

Liver Stiffness Is Associated With Progression of Albuminuria in Adults With Type 2 Diabetes: Nonalcoholic Fatty Disease Cohort Study

ObjectivesPrevious studies have shown the association between liver fibrosis and albuminuria. However, the effect of liver fibrosis on change in albuminuria is unclear. Thus, we investigated the effect of liver fibrosis on change in albuminuria in patients with type 2 diabetes. MethodsIn this retrospective cohort study, we assessed 105 patients with type 2 diabetes concomitant with nonalcoholic fatty disease. A change in urinary albumin excretion (UAE) was defined as follows: change in UAE=(logarithm [UAE+1] at follow-up examination minus logarithm [UAE+1] at baseline examination) / follow-up duration (1 year in this study). Elastography was performed to assess controlled attenuation parameter (dB/m) and liver stiffness measurement (LSM; kPa) values. ResultsMean (standard deviation) data were as follows: age, 63.3 (12.1) years; body mass index, 25.4 (4.3) kg/m2; controlled attenuation parameter, 273.1 (53.0) dB/m; and LSM, 6.2 (3.4) kPa. Median UAE value (interquartile range) was 16 (6 to 43) mg/g creatinine. LSM was associated with changes in UAE (r=0.27, p=0.005). Multiple regression analysis demonstrated that LSM was associated with change in UAE (β=0.28, p=0.015) after adjusting for sex, age, duration of diabetes, smoking status, exercise habits, glycated hemoglobin, body mass index, estimated glomerular filtration rate, systolic blood pressure, logarithm (UAE+1) at baseline examination, use of renin‒angiotensin system inhibitors, new use of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 and controlled attenuation parameter. ConclusionsLiver stiffness is an independent risk factor for the progression of albuminuria in patients with type 2 diabetes.

Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.

Aims/IntroductionThe maximum value of home systolic blood pressure is correlated with damage to target organs, including diabetic nephropathy. However, the precise relationship between the development of diabetic nephropathy and maximum home systolic blood pressure has not been elucidated.Materials and MethodsIn this prospective 2‐year cohort subanalysis of the KAMOGAWA‐HBP study, the patient population was 477 Japanese patients with normoalbuminuria. We investigated the effects of mean and maximum home blood pressure on the development of diabetic nephropathy, which we defined as a urinary albumin excretion value ≥30 mg/g creatinine. Among the 477 patients, 67 developed diabetic nephropathy.ResultsIn our multivariate logistic regression analyses, the maximum morning home systolic blood pressure was significantly positively associated with the development of diabetic nephropathy after adjusting for patient sex and age, smoking status, the diabetes mellitus duration, body mass index, creatinine, total cholesterol, hemoglobin A1c, and antihypertensive medication use (odds ratio 1.21, 95% confidence interval 1.03–1.42, P = 0.021).ConclusionsMaximum home blood pressure can be identified at a glance, and its measurement would thus be helpful to healthcare providers who treat patients with diabetes and normoalbuminuria.

A urinary proteome-based classifier for the early detection of decline in glomerular filtration.

Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be late-stage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m 2 . A total of 2672 patients with different CKD stages were included in the study. Of these, 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m 2 /year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of ≥80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m 2 . In addition, areas under the curve for CKD273 and UAE were calculated. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.

Renal diffusion-weighted imaging in diabetic nephropathy: correlation with clinical stages of disease.

We aimed to assess the correlation between renal apparent diffusion coefficient (ADC) values measured by diffusion-weighted imaging (DWI) and the clinical stages of diabetic nephropathy. DWI (b value, 0 and 600 s/mm2) was performed in 78 patients with clinically confirmed diabetic nephropathy (study group) and 22 volunteers without diabetes mellitus or any renal disease (control group). The mean ADCs were calculated from multiple region-of-interest circles positioned in the renal cortex. Diabetic nephropathy was clinically categorized into five stages based on the values of urinary albumin excretion and glomerular filtration rate (GFR). Mean renal ADC values of patients with stage 3 or 4 disease were significantly lower than those in patients with stage 1 or 2 disease and the control group (P < 0.001). ADC values of patients with stage 5 disease were significantly lower than those in patients with stage 4 (P = 0.003), stage 3 (P = 0.020), stages 2 and 1, and the control group (P < 0.001). Significant correlations were found between mean renal ADC values and clinical stages of diabetic nephropathy (r=-0.751, P < 0.001), between mean renal ADC values and estimated GFR values (r=0.642, P < 0.001), and between mean renal ADC values and urinary albumin excretion (r=-0.419, P < 0.001). Renal ADC values show a significant correlation with clinical stages of diabetic nephropathy. As a relatively simple and noninvasive tool without contrast media administration, renal quantitative DWI may potentially play a role in making clinical decisions in the follow-up of diabetic patients.

A proposal for improving the KDIGO renal disease risk table

Recent surveys have revealed that the prevalence of chronic kidney disease (CKD), particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type-2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation [1]. The diagnosis and management of CKD has been made easier in recent years by the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines of the US National Kidney Foundation. The K/DOQI guidelines advise that CKD can be defined and appropriately managed by a staging approach that relies on estimating the severity of kidney damage based on the degree of proteinuria and impaired kidney function, the latter assessed as a decrease in the glomerular filtration rate (GFR). CKD is defined as kidney damage for [3 months, with or without decreased GFR, manifested by either pathologic abnormalities or markers of kidney damage such as proteinuria 3.4. If there are no signs of kidney damage, a diagnosis of CKD cannot be made until the GFR is\60 mL/min/1.73 m [2]. Using this standard of measure, the National Kidney Foundation estimates that 20 million Americans have CKD, while an additional 20 million are at risk of the disease [3]. During this time, an increasing recognition has emerged about the definition and classification limitations, leading to a heated debate and calls for revisions, mainly in nephrology subspecialty journals. The leadership of KDIGO (Kidney Disease: Improving Global Outcomes), with the endorsement of K/DOQI, convened a Controversies Conference to provide a forum for an open discussion on this problem [4]. One important issue was whether or not the current classification (based on eGFR) should be modified to include additional factors associated with prognosis. The conference generated a table similar to the one used for the European Hypertension Guidelines [5]. It was drawn by a composite ranking of relative risks that enhances communication about prognosis in which colours indicate groups of patients at progressively higher risk for the major outcomes. This table (Fig. 1) would help clinicians, researchers and public health agencies to describe and prioritise efforts aimed at patients and populations at risk of renal disease. The main improvement in the table is to add the value of urinary albumin excretion categorised by N. R. Robles J. F. Macias J. Alvarez-Gregori Cardiovascular Risk Chair, University of Salamanca School of Medicine, Salamanca, Spain

Re: Microalbuminuria in Normal Korean Children

Re: Microalbuminuria in Normal Korean Children

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51-1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68-4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A(1c) influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.

Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) study

Measurement of urinary albumin excretion (UAE) shows important intra-individual variability suggesting the need for multiple assessments. This study aimed at investigating the reproducibility of UAE in type 2 diabetes. UAE was obtained from two to three samples collected in a 3- to 6-month period from 4062 of the 15 773 type 2 diabetic subjects participating in the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study in 2007-08. UAE was assessed as albumin excretion rate (AER) in 24-h urine collections from 833 subjects and albumin:creatinine ratio (A/C) in early-morning urine samples from 3229 patients. Albuminuria was measured by immunonephelometry or immunoturbidimetry. The median coefficient of variation (CV) was 32.5% (interquartile range: 14.3-58.9). Concordance rate between a single UAE and the geometric mean of multiple measurements was 94.6% for normoalbuminuria, 83.5% for microalbuminuria, 91.1% for macroalbuminuria and 90.6% for albuminuria (micro + macro). CV was significantly higher (P < 0.01) for AER measurement than for A/C and with immunoturbidimetry than with immunonephelometry, whereas concordance rates were similar between the two modalities of urine collection and the two assay methods. Receiver-operating characteristic (ROC) plots demonstrated a good performance of single UAE in predicting the geometric mean of multiple measures at the cut-off level of both microalbuminuria (ROC(AUC) 0.926; 95% confidence interval: 0.915-0.937) and macroalbuminuria (ROC(AUC) 0.950; 95% confidence interval: 0.927-0.973). Data from this large cohort indicate that, in type 2 diabetic subjects, a single UAE value, thought to be encumbered with high intra-individual variability, is an accurate predictor of nephropathy stage for clinical and epidemiological purposes.

High Rate of Regression From Micro-Macroalbuminuria to Normoalbuminuria in Children and Adolescents With Type 1 Diabetes Treated or Not With Enalapril

OBJECTIVETo evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE).RESEARCH DESIGN AND METHODSAll diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 ± 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment.RESULTSThe cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 ± 1.0 vs. 9.4 ± 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 ± 11.3 vs. 42.7 ± 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 ± 11.4 vs. 62.4 ± 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients.CONCLUSIONSMicroalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol levels.

Is the reno-protective effect of valsartan dose dependent? A comparative study of 80 and 160 mg day−1

Whether the reno-protective effect of angiotensin receptor blockers is dose dependent is unknown for the Japanese population. We sought to elucidate the dose-dependent reno-protective effects of valsartan in Japanese hypertensive patients with albuminuria. This was a multi-center, open-label, parallel-group trial. A total of 181 patients were randomized to receive either 80 (n=89) or 160 mg day(-1) (n=92) of valsartan for 24 weeks. Then, the effects on blood pressure, urinary albumin excretion (UAE), type IV collagen and beta(2)-microglobulin (beta2MG) were determined. Systolic and diastolic blood pressures decreased substantially by almost the same extent in the low-dose and high-dose groups, showing no inter-group difference during the treatment. The UAE value decreased significantly by 35% in both groups. Urinary excretion of beta2MG was significantly decreased in the high-dose group (17%), but not in the low-dose group (13%), although the decrease was not significantly different between the two groups (P=0.74). Urinary excretion of type IV collagen decreased non-significantly by 10% in the low-dose group and by 8% in the high-dose group, showing no significant inter-group difference (P=0.78). Low (80 mg day(-1)) and high (160 mg day(-1)) doses of valsartan showed a similar effect of lowering blood pressure. The high dose of valsartan resulted in a slightly greater decrease in urinary beta2MG, but it was inconclusive whether the high dose was more reno-protective as compared with the low dose.

Screen-and-treat strategies for albuminuria to prevent cardiovascular and renal disease: Cost-effectiveness of nationwide and targeted interventions based on analysis of cohort data from the Netherlands

Background: Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk. Objective: This study aimed to estimate the costeffectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands. Methods: A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microal-buminuria involved prescreening for UAC ≥20 mg/L, followed by a confirmation test for UAE ≥30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and ≥10, ≥20, ≥100, and ≥200 mg/L) and UAE confirmation test (≥15, ≥30, and ≥300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged ≥50 years, and aged ≥60 years). Results: The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at €926 (€2003 vs €1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at €22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of €20,000, €50,000, and €80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged ≥50 and ≥60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction. Conclusions: Our analyses suggest the potentially favorable cost-effectiveness of population-based screening for albuminuria in the general Dutch population. The results offer health care decision-makers new tools for considering actual implementation of such screening.

IN RESISTANT HYPERTENSION, A CUTOFF FOR URINARY ALBUMIN EXCRETION LOWER THAN THE CURRENT DEFINITION OF MICROALBUMINARIA IS SIGNIFICANTLY ASSOCIATED WITH BLOOD PRESSURE: PP.35.446

Microalbuminuria (MA) is a target organ damage marker that correlates with true resistant hypertension (T-RH) better than with isolated office-resistant hypertension (IO-RH). The best cutoff value for urinary albumin excretion (UAE) to discriminate between both groups remains undetermined. Objective: To determine the cutoff value of UAE that better identifies patients with T-RH with respect to subjects with IO-RH. Design and Method: 529 RH patients were consecutively recruited from Spanish Hypertension Units. Inclusion criteria: age>18yr, office-RH diagnosis (BP> = 140 and/or 90mmHg despite treatment with >=3 drugs, diuretic included), secondary hypertension ruled-out, glomerular filtration rate > 30 mL/min/1,73m2. All subjects underwent laboratory evaluation and 24h-ABPM. We defined IO-RH if office-BP >=140 and/or 90mmHg and 24h-ABPM <130/80mmHg. UAE: average of three first-morning-void urine determinations of urinary albumin/creatinine ratio. The best cutoff value of UAE associated with T-RH was assessed by ROC curve analysis. Student't test was used to compare the associations of the new found and classical UAE cutoff values, with 24h-ABPM and office-BP measures. Results: area under ROC curve: 0.66[IC95%:0.59–0.73;p < 0.001]; best cutoff: UAE=15 mg/g. Patients were categorized for MA according to: (A):UAE>=22 mg/g(males) or >=31(females); (B):UAE>=30; (C):UAE>=15. Bivariate analysis: there was no significant association of office-SBP or office-DBP and patients with MA according to A, B or C criteria. Day-SBP was significantly higher in patients with MA according to C (144.8 ± 17.5 vs. 138.7 ± 17.3;p = 0.0014) but not according to A or B. Both day-DBP and night-SBP, night-DBP, 24h-SBP and 24h-DBP were significantly associated with MA as defined by A, B or C criteria. Conclusions: 1)both office-SBP and -DBP poorly correlate with UAE, in comparison to the excellent association of UAE with 24h-ABPM measures, reinforcing the key role of 24h-ABPM to identify patients with T-RH but also to detect those with more target organ damage. 2) cutoff value of 15 mg/g for MA appears to have a better discrimination power to identify patients with T-RH, detecting those with high day-SBP better than when current accepted cutoff values for MA are used.

Renal Function Following Long-Term Weight Loss in Individuals with Abdominal Obesity on a Very-Low-Carbohydrate Diet vs High-Carbohydrate Diet

A frequently cited concern of very-low-carbohydrate diets is the potential for increased risk of renal disease associated with a higher protein intake. However, to date, no well-controlled randomized studies have evaluated the long-term effects of very-low-carbohydrate diets on renal function. To study this issue, renal function was assessed in 68 men and women with abdominal obesity (age 51.5±7.7 years, body mass index [calculated as kg/m 2] 33.6±4.0) without preexisting renal dysfunction who were randomized to consume either an energy-restricted (∼1,433 to 1,672 kcal/day), planned isocaloric very-low-carbohydrate (4% total energy as carbohydrate [14 g], 35% protein [124 g], 61% fat [99 g]), or high-carbohydrate diet (46% total energy as carbohydrate [162 g], 24% protein [85 g], 30% fat [49 g]) for 1 year. Body weight, serum creatinine, estimated glomerular filtration rate and urinary albumin excretion were assessed before and after 1 year (April 2006-July 2007). Repeated measures analysis of variance was conducted. Weight loss was similar in both groups (very-low-carbohydrate: −14.5±9.7 kg, high-carbohydrate: −11.6±7.3 kg; P=0.16). By 1 year, there were no changes in either group in serum creatinine levels (very-low-carbohydrate: 72.4±15.1 to 71.3±13.8 μmol/L, high-carbohydrate: 78.0±16.0 to 77.2±13.2 μmol/L; P=0.93 time × diet effect) or estimated glomerular filtration rate (very-low-carbohydrate: 90.0±17.0 to 91.2±17.8 mL/min/1.73 m 2, high-carbohydrate: 83.8±13.8 to 83.6±11.8 mL/min/1.73 m 2; P=0.53 time×diet effect). All but one participant was classified as having normoalbuminuria at baseline, and for these participants, urinary albumin excretion values remained in the normoalbuminuria range at 1 year. One participant in high-carbohydrate had microalbuminuria (41.8 μg/min) at baseline, which decreased to a value of 3.1 μg/min (classified as normoalbuminuria) at 1 year. This study provides preliminary evidence that long-term weight loss with a very-low-carbohydrate diet does not adversely affect renal function compared with a high-carbohydrate diet in obese individuals with normal renal function.

Plasma serotonin is a predictor for deterioration of urinary albumin excretion in men with type 2 diabetes mellitus

We performed an observational study to investigate if plasma 5-hydroxyindole-3-acetic acid (5-HIAA), a derivative end product of serotonin (5-hydroxytryptamine), concentration could be a predictor for deterioration of urinary albumin excretion. The relationship between baseline plasma 5-HIAA concentration and changes in urinary albumin excretion for 24 months was investigated in 162 male patients with type 2 diabetes mellitus. Patients were divided into tertiles according to plasma 5-HIAA concentration. Greater changes in urinary albumin excretion were seen in patients with high plasma 5-HIAA concentration (112.8 ± 36.2 mg/g creatinine) than in patients with low plasma 5-HIAA concentration (7.6 ± 8.0 mg/g creatinine, P = .0011) or in patients with intermediate plasma 5-HIAA concentration (25.6 ± 15.0 mg/g creatinine, P = .0070) after adjustment for baseline values of urinary albumin excretion. A positive correlation was observed between log (plasma 5-HIAA concentration) and changes in urinary albumin excretion ( r = 0.314, P < .0001). Multiple regression analysis demonstrated that log (plasma 5-HIAA concentration) ( β = .284, P = .0013) was an independent determinant of changes in urinary albumin excretion. In conclusion, plasma 5-HIAA concentration was positively correlated with changes in urinary albumin excretion, which may indicate causality in diabetic nephropathy in male patients with type 2 diabetes mellitus and high plasma 5-HIAA concentration.