Urinary Albumin Excretion In Patients Research Articles

Urinary albumin excretion in patients with rheumatoid arthritis in a large cross-sectional study

While there is a lot of evidence published on the association of cardiovascular (CV) disease and rheumatoid arthritis (RA), little is known about urinary albumin excretion (UAE)-a marker of CV risk-in this particular high-risk population. Therefore, we investigated UAE in a large cross-sectional study. We used data from the US National Health and Nutrition Examination Survey (NHANES), including the years 2007-2012. Primary outcome was the proportion of patients with a urinary albumin-creatinine ratio (ACR) >30mg/g. A total of 14,648 study participants (representing a population size of 174,663,008) with available ACR were included in the study (14,179 without RA and 469 with RA). In the RA group, the proportion of patients with an ACR >30mg/g was 10.46% (95% CI 7.47-14.45%) and in the non-RA group this proportion was 13.39% (95% CI 12.65-14.16%; p = 0.09). There was a strong association between RA and DM (OR 5.84; 95% CI 4.48-7.62). In the RA group, significantly more patients had a former CV event (OR 3.01; 95% CI 2.28-3.97). Adjustments for DM, smoking status, former CV event, age, systolic blood pressure, and gender did not substantially alter the association between RA and ACR >30mg/g (OR 0.82; 95% CI 0.51-1.33). We did not find evidence for a difference in UAE in patients with or without RA, despite the fact that RA was associated with DM and, in addition, RA patients more often had a previous CV event. These findings may support the assumption that despite an increased CV risk, UAE does not play a major role in RA patients.

Usefulness of the renal resistive index to predict an increase in urinary albumin excretion in patients with essential hypertension.

Microalbuminuria is a risk factor for cardiovascular events and death in hypertensive patients. Patients who are expected to increase albuminuria need strict blood pressure control. In the present study, we assessed the association between the renal resistive index (RI) and future increases in albuminuria in patients with essential hypertension. Sixty-six patients with essential hypertension were included in the study. Univariate and multivariate logistic regression analyses were used to identify the factors, including renal RI, that were significant independent determinants of increased in urinary albumin excretion (UAE), defined as an increase of >50% in the urinary albumin-to-creatinine ratio over 2 years. Receiver operator characteristics curve analysis was used to select the optimal cut-off point that predicted an increase in UAE. RI was the only significant variable that predicted the increase in UAE, with the optimal cut-off value of renal RI that predicted this increase being 0.71 (sensitivity 52.4% and specificity 84.4%). Renal RI is associated with the future increase in albuminuria in patients with essential hypertension.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus.

Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross-sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, P<.0001) or central SBP (r=0.227, P<.0001) was associated with UAE. Multiple logistic regression analysis demonstrated that peripheral SBP (odds ratio, 1.029; 95% confidence interval, 1.016-1.043) or central SBP (odds ratio, 1.022; 95% confidence interval, 1.011-1.034) was associated with an increased odds of albuminuria. In addition, AUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes.

Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.

PLASMA ENDOTHELIN-1 LEVELS AND ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Microalbuminuria is a very important independent risk factor for the progression of renal diseases as well as diseases of the cardiovascular system. Pathophysiological mechanisms that lead to the development ofmicroalbuminuria in patients with diabetes are complex and they are a result of numerous factors. In the past decade, endothelin-1, the most potent vasoconstrictor peptide, was identified as animportant factor that significantly contributes to the functional and structural renal changes. The objective of this study was to investigate the relationship between plasma concentration of endothelin-1 and urinary albumin excretion in patients with type 2 diabetes mnellitus. There were 76 patients with type 2 diabetes who were divided into those having normoalbuminuria (n-33), microalbuminuria (n=29) and macroalbuinuria (n=14), and 30 healthy controls. Plasma levels of endothelin-1 were measured by enzyme-linked immunosorbent assay. There were significant differences in plasma concentration of endothelin-1 among groups (P<0.01). The correlation between endothelin-1. albuminuria. proteinuria and glomercular filtration rate was significant. In multiple regression analyses the plasma concentration of endothelin-l was independently and significantly associated with albuminuria (β=0.01, p=0.009), proteinuria =.02, p<0.001) and glon.erular filtration rate (P3=0βl. pO-.P=)6).0Conclu- sion. Higher plasma concentrations of endothelin-1 are independently associated with the levels of urinary, excretion of albumin Whicw May morroborate tlse hpothesis of apotenstial role of this peptide inl th de- vepment of microalbUminuriauin diabetic necphrpathy.

Bariatric surgery reduces urinary albumin excretion in diabetic nephropathy: a systematic review and meta-analysis

BackgroundBariatric surgery is found to prevent type 2 diabetes, improve glycemic control, and decrease long-term incidence of microvascular and macrovascular complications in obese persons. However, its effect on urinary albumin excretion (UAE) in patients with diabetic nephropathy (DN) is still unknown. This is a systematic review and meta-analysis of observational studies on bariatric surgery and change in UAE in patients with diabetes. ObjectiveTo explore whether there is improvement in UAE after bariatric surgery. MethodsWe comprehensively searched the databases of MEDLINE, Embase, and Cochrane. The inclusion criteria were published studies evaluating effects of bariatric surgery in patients with DN at baseline. The primary outcome was the pre- and postbariatric surgery UAE as characterized by urinary albumin-to-creatinine ratio and albuminuria. A meta-analysis comparing pre- and postsurgery UAE was performed. ResultsFrom 65 full-text articles, 15 observational studies met our inclusion criteria, and 11 studies were included in the meta-analysis based on the random effects model. There was a significant reduction in urinary albumin-to-creatinine ratio after bariatric surgery with a mean difference of –6.60 mg/g of creatinine (95% CI –9.19 to –4.02; P<.001). There was also a reduction in albuminuria with a mean difference of –55.76 mg/24 hours (95% CI –92.11 to –19.41; P<.001) after bariatric surgery. ConclusionBariatric surgery significantly decreases urinary albumin excretion in DN. However, studies comparing bariatric surgery and conventional or intensive care of diabetes on UAE outcome should be done.

Optimal home SBP targets for preventing the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined. We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus. Logistic regression models were used to evaluate the correlations of home SBP levels with progression of diabetic nephropathy. During the follow-up of 2 years, 86 patients had progression of diabetic nephropathy. Adjusted odds ratios (95% confidence interval) for progression of diabetic nephropathy in patients with morning SBP of 120-129 mmHg [2.725 (1.074-6.917), P = 0.035], 130-139 mmHg [3.703 (1.519-9.031), P = 0.004] and in those with morning SBP equal or more than 140 mmHg [2.994 (1.182-7.581), P = 0.021] were significantly higher than that in those with morning SBP less than 120 mmHg in multiple logistic analyses. The preferable morning SBP targets might be less than 120 mmHg for preventing the onset or progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitus

AimsAlthough relationships of serum bilirubin concentration with estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) in patients with type 2 diabetes have been reported, whether such relationships exist in patients with type 1 diabetes is unknown. MethodsA total of 123 patients with type 1 diabetes were investigated in this cross-sectional study. The relationship between bilirubin (total and indirect) concentrations and log(UAE) as well as eGFR was examined by Pearson’s correlation analyses. Multivariate regression analyses were used to assess the association of bilirubin (total and indirect) with eGFR as well as log(UAE). ResultsA positive correlation was found between serum bilirubin concentration and eGFR; total bilirubin (r=0.223, p=0.013), indirect bilirubin (r=0.244, p=0.007). A negative correlation was found between serum bilirubin concentration and log(UAE); total bilirubin (r=−0.258, p=0.005), indirect bilirubin (r=−0.271, p=0.003). Multivariate regression analyses showed that indirect bilirubin concentration was an independent determinant of eGFR and log(UAE). ConclusionsBilirubin concentration is associated with both eGFR and log(UAE) in patients with type 1 diabetes. Bilirubin might have a protective role in the progression of type 1 diabetic nephropathy.

Association of Soluble Receptor for Advanced Glycation End Products Levels with Hypertensive Albuminuria

Soluble receptor for advanced glycation end products (sRAGE) levels have been found to be decreased in chronic inflammatory diseases including atherosclerosis, hypertension and renal failure. This study evaluated the relationship between sRAGE concentrations and urinary albumin excretion in patients with essential hypertension. A total of 200 consecutive patients with essential hypertension were enrolled and were divided into 3 groups. Plasma sRAGE levels were significantly lower in hypertensive patients with micro- or macroalbuminuria compared with those in hypertensive patients with normoalbuminuria, and the values in the macroalbuminuria group were even lower than in the microalbuminuria group (128.6±24.2, 244.6±37.6±313.6±30.7 pg/ml, respectively). In addition, plasma sRAGE level was an independent determinant of log urinary albumin excretion in patients with essential hypertension (β=-0.267, P<0.05). sRAGE may play a role in the pathogenic processes that link albuminuria, chronic inflammation and oxidative stress in hypertensive patients.

Plasma osteoprotegerin concentrations in type 1 diabetic patients with albuminuria

BackgroundOsteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in diabetes. AimTo investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in type 1 diabetes. MethodsA total of 80 type 1 diabetic subjects and 40 control subjects were enrolled. Diabetic subjects were divided into a normoalbuminuric group and a microalbuminuric group according to urinary albumin excretion rate (UAER). Plasma OPG level was measured by enzyme-linked immunoassay. ResultsThe plasma OPG levels were significantly elevated in patients with microalbuminuria (176.39±25.05pg/ml) compared with patients with normoalbuminuria (154.73±16.66pg/ml) and control subjects (44.76±8.7pg/ml). The plasma OPG level had a positive correlation with patients' age, duration of disease, HbA1C and UAER. ConclusionsPlasma OPG levels are significantly associated with UAE in patients with type 1 diabetes. These findings may support the concept that elevated plasma OPG may be associated with diabetic angiopathy.

Retinal Nerve Fiber Layer Loss Is Associated with Urinary Albumin Excretion in Patients with Type 2 Diabetes

To identify the factors associated with retinal nerve fiber layer (RNFL) loss in patients with type 2 diabetes. Cross-sectional study. Ninety-six nonglaucomatous patients with type 2 diabetes without renal impairment (estimated glomerular filtration rate, ≥60 ml/minute per 1.73 m(2)). Eyes were divided into 2 groups based on the presence or absence of RNFL defects detected by red-free retinal fundus photography. All participants underwent an eye fundus examination, and the urinary albumin-to-creatinine ratio (ACR) was determined. A cardiovascular autonomic function test was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to the Valsalva maneuver, and standing. Multiple logistic regression analyses were performed to determine potential risk factors related to the presence of RNFL defects in these patients. The association between RNFL defects and diabetic complications. Among the patients, 43 (44.8%) had localized RNFL defects (group 1), whereas the others (55.2%) did not (group 2). The RNFL defects occurred more frequently on the superior side (75.6% and 71.0% in right and left eyes, respectively) compared with the inferior side (13.8% and 0.0% in right and left eyes, respectively). Patients with RNFL defects (group 1) had significantly higher rates of diabetic retinopathy (60.5%) compared with those without RNFL defects (group 2; 32.1%; P = 0.007). The urinary ACR was significantly higher in patients with RNFL defects than in those without defects (45.3±72.1 μg/mg vs. 15.4±17.3 μg/mg creatinine, respectively; P = 0.015), whereas autonomic function test grading was similar between the groups. The urinary ACR was the only factor related to visual field defect location in both univariate (P = 0.021) and multivariate (P = 0.036) logistic regression analyses after adjusting for age; gender; presence of diabetic retinopathy; diabetes duration; smoking; statin use; and antiplatelet, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment. Urinary albumin excretion was associated with nerve fiber layer loss in patients with type 2 diabetes. Careful examination of the optic nerve head may be necessary, particularly in patients with type 2 diabetes exhibiting albuminuria.

Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes

AimIrisin is first discovered as a potential mediator of obesity related energy homeostasis. Recent studies indicate that irisin is associated with endothelial dysfunction and atherosclerosis in patients with type 2 diabetes. Our objective was to examine the relationship between irisin and urinary albumin excretion in patients with type 2 diabetes. Methods100 newly diagnosed patients with type 2 diabetes and 100 healthy subjects were selected. Serum irisin levels were measured by ELISA, and urine albumin was measured by radioimmunoassay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated arterial dilation, FMD) and after sublingual glyceryltrinitrate. ResultsPatients with type 2 diabetes presented decreased irisin levels when compared to controls (14.12±3.93 versus 28.98±2.56ng/ml, P=0.015).Serum irisin levels in the microalbuminuric and macroalbuminuria subgroup were 9.89±1.56ng/ml and 5.67±1.89ng/ml, respectively, which were significantly lower than those in the normoalbuminuria (15.97±3.12ng/ml). In comparison to microalbuminuric subgroup, macroalbuminuria subgroup had lower levels of irisin. By dividing the distribution of serum irisin levels into quartiles, FMD was increased gradually with the increase of serum irisin levels (P<0.001). Multiple stepwise linear regression analysis showed that FMD (β=0.75, P=0.002), 2-hBG (β=−0.25, P=0.038) and UAE (β=−0.87, P=0.008) were significantly associated with irisin. Pearson's correlation analyses showed a negative correlation between irisin and logUAE (r=−0.57) and between FMD and logUAE (r=−0.47), and positive correlations between irisin and FMD (r=0.51). ConclusionsDecreased plasma levels of irisin seem to be associated with UAE and FMD in patients with type 2 diabetes.

Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial.

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m(2) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2) in the control group, with a between-group difference of 4.3 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m(2); P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m(2) per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, -0.3% to 11.1%) in the control group and -14.9% (95% CI, -20.4% to -9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.

Association between Sleep Duration and Urinary Albumin Excretion in Patients with Type 2 Diabetes: The Fukuoka Diabetes Registry

ObjectiveFew studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients.Research Design and MethodsA total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5–5.4 hours, 5.5–6.4 hours, 6.5–7.4 hours, 7.5–8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally.ResultsBoth short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5–7.4 hours (P for quadratic trend <0.001). A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms.ConclusionsOur findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.

Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes

AimUrinary adiponectin (u-adiponectin) excretion has been suggested to reflect early glomerular damage. Inspired by this, we studied the levels of u-adiponectin in type 1 diabetic patients with different levels of urinary albumin excretion (UAE). MethodsU-adiponectin was analysed by ELISA in type 1 diabetic patients: Fifty-eight with normoalbuminuria (<30mg albumin/24h), 43 with persistent microalbuminuria (30–300mg/24h) and 44 with persistent macroalbuminuria (>300mg/24h). For comparison, a control group of 55 healthy individuals was included. ResultsU-adiponectin increased with increasing levels of UAE (p<0.01). U-adiponectin median (interquartile range): Normoalbuminuria 0.38 (0.14–1.31), microalbuminuria 1.12 (0.20–2.68), macroalbuminuria 9.20 (1.10–23.35) and controls 0.09 (0.06–0.24) μg/g creatinine. Levels were unrelated to sex, age, cholesterol, diastolic BP and BMI. U-adiponectin was weakly associated with increasing systolic BP and HbA1c (r2<0.1, p<0.05), but strongly related to increasing UAE (r2=0.57, p<0.001) and decreasing eGFR (r2=0.26, p<0.001). The relationship between UAE and u-adiponectin was significant in all groups and independent of eGFR, BMI, BP and HbA1c. Furthermore, u-adiponectin was associated with markers of tubular damage (p<0.01). ConclusionU-adiponectin rises with increasing levels of UAE in patients with type 1 diabetes. This is in accordance with the hypothesis that loss of adiponectin may reflect glomerular and/or tubular damage.

Azelnidipine versus diuretic against albuminuria used in combination with angiotensin receptor blocker in hypertensive patients with diabetes

Purpose: A thiazide diuretic used in combination with an angiotensin converting enzyme inhibitor, benazepril, more effectively reduces urinary albumin as compared to amlodipine plus benazepril in patients with hypertension and diabetes. However, calcium channel blockers have diverse characteristics. The present study was designed to test the hypothesis that combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. Methods: This was a 24-week prospective randomized open blinded endpoint study assessing the effects of azelnidipine versus those of a diuretic in combination with an angiotensin receptor blocker, olmesartan, on urinary albumin excretion in patients with hypertension and diabetes. Patients with hypertension, type 2 diabetes, and albuminuria (30–600 mg/g creatinine) under antihypertensive treatment (mean age, 67.0±7.6 years) were recruited. They were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg, daily) and amlodipine (5 mg, daily) for 12 weeks (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus trichlormethiazide (1 mg/day; n=72) for an additional 24 weeks, with the endpoint being urinary excretion of albumin. Results: At the time of randomization, the blood pressures was 135±12/75±10 and 135±12/76±9 mmHg and urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively. Urinary albumin excretion was reduced to a similar extent in the azelnidipine (79.8 [95% confidence interval 66.4–96.0] mg/g creatinine) and diuretic regimen (89.7 [74.6–107.7] mg/g creatinine) after adjustment for baseline values, while glomerular filtration rate was reduced only in the diuretic group. There were no significant differences in blood pressure between the two arms throughout the treatment period (at 24 weeks 133±10/74±8 and 134±11/74±10 mmHg in the azelnidipine and diuretic regimens, respectively). Conclusion: Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan though the calcium channel blocker does not reduce glomerular filtration rate.

Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension

Mineralocorticoid receptor antagonists (MRAs) are commonly used to reduce blood pressure, left-ventricular hypertrophy, and urinary albumin excretion in patients with essential hypertension or primary aldosteronism. Effects of MRAs on hypertensive organ damage seem to occur beyond what is expected from the mere reduction of blood pressure. This suggests that activation of the mineralocorticoid receptor plays a central role in the development of cardiac and renal abnormalities in hypertensive patients. However, broad use of classic MRAs such as spironolactone has been limited by significant incidence of gynecomastia and other sex-related adverse effects. To overcome these problems, new aldosterone blockers have been developed with different strategies that include use of nonsteroidal MRAs and inhibition of aldosterone synthesis. Both strategies have been designed to avoid the steroid receptor cross-reactivity of classic MRAs that accounts for most adverse effects. Moreover, inhibition of aldosterone synthesis could have an additional benefit due to blockade of the mineralocorticoid receptor-independent pathways that might account for some of the untoward effects of aldosterone. The new aldosterone blockers are currently having extensive preclinical evaluation, and one of these compounds has passed phase 2 trials showing promising results in patients with primary hypertension and primary aldosteronism. This narrative review summarizes the knowledge on the use of classic MRAs in hypertension and covers the evidence currently available on new aldosterone blockers.

Reduction in Morning Blood Pressure Is a Key Factor for Ameliorating Urinary Albumin Excretion in Patients With Morning Hypertension Irrespective of Treatment Regimen

The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.

Prevalence of haematuria positively associated with urine albumin excretion in Type 2 diabetes

Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7% (n = 13), 16.1% (n = 67) and 35.8% (n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria.