Levels Of Urinary Albumin Excretion Rate Research Articles

Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study.

To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM). According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively. To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [β = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [β = -1.633, 95% CI (-2.77, -0.496)] and Tf [β = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, p =0.015 and 0.001], and Tf (OR = 0.109 and 0.119, p =0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both p <0.001) in the MA group. DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.

Resistant hypertension: a therapeutic challenge.

Resistant hypertension: a therapeutic challenge.

Prognostic impact of baseline urinary albumin excretion rate in patients with resistant hypertension: a prospective cohort study.

Moderately increased albuminuria, defined as urinary albumin excretion rate (UAER) between 30 and 300-mg/24-h is a well-known cardiovascular risk factor, especially in diabetic and hypertensive patients. This study aim to analyze the prognostic value of baseline UAER in a still understudied group, patients with resistant hypertension (RHT). This is a prospective observational study, which had enrolled 1048 outpatients with RHT, who were submitted to a clinical-laboratory assessment and ambulatory blood pressure monitoring (ABPM) during the follow-up. Primary endpoints were a composite of fatal and non-fatal cardiovascular events, all-cause mortality and cardiovascular mortality. Survival analysis by multiple Cox regression assessed the associations among endpoints, baseline UAER, glomerular filtration rate (GFR), and ABPM control. After a mean 7.5 years follow-up, 233 patients died, 120 from cardiac death; 215 cardiovascular events occurred, 90 strokes and 116 coronary diseases. UAER above 30-mg/24-h increased above 40% the risk of fatal and non-fatal cardiovascular events, and of all-cause mortality. At these UAER levels, secondary outcomes were associated to increased risk of stroke and risk of end-stage renal disease, but did not affect coronary events. Both the GFR below 60-mL/min and uncontrolled ABPM were related to nearly two-fold raised risk of fatal and non-fatal cardiovascular events, when coupled with UAER above 30-mg/24-h. In conclusion, moderately increased albuminuria predicts cardiovascular events and all-cause mortality in RHT, and its prognostic impact is enhanced in association with a GFR under 60-mL/min and uncontrolled baseline ABPM.

The effect of L-thyroxine substitution on oxidative stress in early-stage diabetic nephropathy patients with subclinical hypothyroidism: a randomized double-blind and placebo-controlled study.

To study oxidative stress status of early type 2 diabetic nephropathy (DN) patients with subclinical hypothyroidism (SCH) and to assess effect of L-thyroxine therapy on the oxidative stress in these patients. It is a randomized double-blind and placebo-controlled trial. A total of 48 patients with early type 2 DN were included as Euthyroid group, and 92 early type 2 DN with SCH were selected and randomly assigned to L-thyroxine treatment group (LT4 group) and placebo group (SCH group). Changes in urinary albumin excretion rate (UAER), serum malondialdehyde (MDA), superoxide dismutase (SOD) activity, urine 8-hydroxyl deoxyguanosine (8-OHdG), serum creatinine, estimated glomerular filtration rate, and lipid profile before and after 24weeks of follow-up were examined and compared. The levels of UAER, MDA, 8-OHdG were higher, while the SOD activity was lower in DN patients with SCH than in DN patients (p<0.05 for all). In the LT4 group, the levels of UAER, MDA, 8-OHdG decreased significantly (p<0.05) to levels no longer different from the Euthyroid group. The SOD activity increased significantly. But in SCH group, the levels of mAlb, MDA, 8-OHdG were greater after 24weeks of follow-up and greater than patients in the Euthyroid group. SOD activity decreased significantly after 24weeks in the SCH group (p<0.05). Oxidative stress is greater in the DN patients with SCH, and SCH may exacerbate kidney injury in early DN patients. The LT4 treatment may decrease the oxidative stress and attenuate renal injury in DN patient with SCH.

Decreased Activated Protein C Levels are Inversely Associated with the Urinary Albumin Excretion Rate in Patients with Type 2 Diabetes

Activated protein C (APC) plays a vital renoprotective role against diabetic nephropathy in STZ-induced diabetic mice by inhibiting endothelial cell and podocyte apoptosis. This study aimed to examine the relationship between the degree of albuminuria and APC levels in patients with type 2 diabetes. Ninety-four patients with type 2 diabetes and 38 healthy subjects were recruited into this study. The urinary albumin concentrations of urine collected over 24 hours were measured by ELISA to evaluate the mean urinary albumin excretion rate (UAER). The HbA1c levels were determined using an HPLC assay. There was no significant difference in the APC levels between diabetic patients with normoalbuminuria and controls, although APC levels were significantly lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) or macroalbuminuria (8.06 +/- 10.09 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) as compared to control subjects. In addition, in comparison to diabetic patients with normoalbuminuria, APC levels were lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 55.69 +/- 31.98 pg/mL, p < 0.05) and they were the lowest in diabetic patients with macroalbuminuria (8.06 +/- 10.09 vs. 55.69 +/- 31.98 pg/mL, p < 0.05). Multivariate regression and ROC analysis found that the levels of APC and HbA1c were independent risk factors for UAER levels (R2(ad) = 0.61, f = 25.69, p < 0.01) and the value of APC < or = 41.588 pg/mL indicated elevated albuminuria in patients with type 2 diabetes. Decreased APC levels in patients with type 2 diabetes may serve as a biomarker to indicate the early development of diabetic nephropathy.

Visceral obesity is associated with higher urinary albumin excretion levels in normoalbuminuric type 2 diabetic patients

To analyze the relationship between visceral obesity and urinary albumin excretion rate (UAER). A cross-sectional study of 73 normoalbuminuric (urinary albumin excretion rate < 20 microg/min) type 2 patients was performed. Patients were divided into two groups according to the median of UAER (7.5 microg/min). Office auscultatory blood pressure was measured in sitting position after a 10-min rest. Waist to hip ratio was higher in the group with UAER > 7.0 microg/min (0.98 +/- 0.08), when compared to the other group (0.93 +/- 0.08, p= 0.01). Waist to hip ratio significantly correlated with UAER (r = 0.28; p= 0.018). In multiple linear regression analysis, only waist to hip ratio was associated with UAER (r = 0.29; p = 0.04). A1c, DM duration and systolic BP levels were excluded from the model. Type 2 normoalbuminuric diabetic patients with higher levels of UAER could represent a group with an elevated risk for the development of cardiovascular diseases.

Ambulatory blood pressure monitoring and progression of retinopathy in normotensive, normoalbuminuric type 1 diabetic patients: A 6-year follow-up study

To investigate the relationship between diabetic retinopathy (DR) and 24-h ambulatory blood pressure (ABP) in a cohort of normotensive, normoalbuminuric type 1 diabetic patients. This is a 6.1 ± 3.3 year prospective study of 44 normotensive, normoalbuminuric type 1 diabetic patients. ABP was measured at the beginning and at the end of the study. Measurements of urinary albumin excretion rate (UAER) and direct and indirect ophthalmoscopy after mydriasis were performed at the start and end of the study and at least once a year. DR was observed in 12 patients at baseline. At the end of the study, eight of these patients had progressed to more advanced stages of retinopathy. Four patients developed retinopathy after the study began. These patients were grouped and classified as progressors. At baseline, progressors were older, had longer duration of diabetes, higher levels of UAER, and higher 24-h diastolic ( P = 0.03) and diurnal diastolic blood pressure ( P = 0.03). UAER and diastolic blood pressure (24 h or day) remained significantly associated with development and progression of DR after multivariate analysis. High normal ABP was associated with the development or progression of DR in this cohort of normotensive, normoalbuminuric type 1 diabetic patients. Abnormalities in blood pressure homeostasis could indicate higher susceptibility to DR.

A prospective study of cardiovascular disease in patients with Type 2 diabetes: 6.3 years of follow-up

Objective: Type 2 diabetes mellitus (DM-2) is an important cardiovascular risk factor, although hardly any data are available in our country. Therefore, we decided to study the incidence of cardiovascular disease (CVD) and the related variables with its appearance in a group of patients with DM-2. Research design and methods: 176 DM-2 patients without CVD at baseline (63.6% women, mean age 54±8.9), mean follow-up 6.3 years. We collected data at 6-month intervals concerning new micro- and macrovascular complications, glucose, HbA 1C, lipid profile, and renal function. We analyzed values at baseline and at the end of follow-up. For numeric variables, the mean value during follow-up was calculated. In renal function variables, we also worked out the difference between baseline and final values, considering the time until the first episode of CVD as the independent variable. Kaplan–Meier analysis was used in categorical variables and Cox regression tests for numeric data and also for multivariate analysis. In multivariate analysis, we included significant data in the univariate analysis, excluding those from the end of the follow-up with the aim of having some predictive meaning in our results. Results: New episodes of CVD were detected in 28 patients (15.9%). These events were statistically related with baseline diagnosed hypertension, presence of diabetic nephropathy and retinopathy, HbA 1C, and total cholesterol. Among mean values during follow-up, the association was with HbA 1C, cholesterol, urinary albumin excretion rate (UAER), glomerular filtration rate (GFR), and systolic arterial pressure. There was also a relationship of CVD events with the new appearance or worsening of diabetic retinopathy or nephropathy, creatinine and UAER increase and the decrease of GFR and effective renal plasma flow (ERPF), during follow-up. In the multivariate analysis, we found an independent association with the appearance of CVD and mean HbA 1C, mean UAER and the presence of proliferative diabetic retinopathy at baseline. Conclusions: We have a rather low incidence of CVD in our patients with DM-2. The appearance of CVD is independently related with HbA 1C, the level of UAER, and the presence at baseline of diabetic retinopathy.

ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: A 10-year prospective study

The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2±2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR (51Cr-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7±0.6-year intervals. The presence of ACE gene I/D and PC-1 gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R2=.15, F=4.92, P=.035) of the observed GFR decline (−0.29±0.34 ml/min/month, P<.05). UAER increased during the study (log UAER=0.0275±0.042 μg/min/month, P=.002) and was associated with baseline UAER levels only (R2=.17, F=5.72, P=.024). A significant increase (P<.05) in cases of hypertension and retinopathy were observed in ID/DD (n=19) and not in II patients (n=11). Patients with the KQ/QQ genotype (n=8) presented a significant increase (P=.045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension.

Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients.

To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.

Initial urinary albumin excretion determines the progression of microalbuminuria in patients with type-2 diabetes and normotensive blood pressure values despite improved metabolic control

Persistent increased urinary albumin excretion rate (UAER) is associated with increased cardiovascular mortality in type-2 diabetes, however, there are no conclusive data about the progression of advanced UAER in these patients. The present study has investigated the effect of metabolic intervention on the progression in UAER in relation to initial UAER levels. A total of 20 patients with type-2 diabetes and secondary failure to sulfonylurea were observed during 1 year (age, 60±8 years; HbA 1c, 10.8±1.4%; and duration of diabetes, 17±10 years) and divided into two groups: group 1 ( n=10; UAER: 51±35 mg/24 h); and group 2 ( n=10; UAER: 191±175 mg/24 h). Despite a significant improvement of metabolic control by insulin treatment in both groups (HbA 1c: group1: 11±1.5 vs. 7.9±1.2%; group 2: 10.6±0.9 vs. 9.1±1.3%, P<0.001), a progression of UAER was observed in group 2 (191±175 vs. 331±237 mg/24 h, P<0.02), but not in group 1 (51±35 vs. 41 + ̄ 24 mg/24 h). Still serum creatinine levels remained normal in all patients during the observation period. The 24 h blood pressure (RR) values in the two groups remained normal under antihypertensive therapy throughout the study (group 1: RR syst: 130 vs. 136 mmHg; RR diast: 80 vs. 81 mmHg, mean arterial pressure (MAD): 89 vs. 93 mmHg; group 2: RR syst: 139 vs. 134 mmHg; RR diast: 78 vs. 75 mmHg, MAD: 97 vs. 90 mmHg). The data shows that in type-2 diabetic patients with normotensive blood pressure values the initial urinary albumin excretion levels determine the progression of UAER. When metabolic control is improved incipient UAER remains constant, but advanced UAER shows progression.

Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects

To investigate the metabolic and renal effects of the nonsulfhydryl, tissue-active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30 essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM) subjects with hypertension. Systolic and diastolic blood pressures, plasma glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and urinary albumin excretion were evaluated before and after 8 weeks' administration of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable reduction of arterial blood pressure in both groups. Mean arterial pressure decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the diabetic hypertensive group. In both essential hypertensives and diabetic-hypertensive subjects with microalbuminuria, quinapril significantly and comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from 32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline) in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6 +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives. Altogether, a direct correlation was found between the initial level of UAE and the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and glucose responses to an oral glucose tolerance test and the lipid profiles were not modified by quinapril treatment. The results confirm that quinapril is an effective antihypertensive agent that additionally reduces microalbuminuria in both hypertensive diabetics and in patients with essential hypertension, without altering insulin sensitivity and lipid profiles.

Urinary albumin excretion in a population based sample of 1011 middle aged non-diabetic subjects. The Copenhagen City Heart Study Group.

Increased urinary albumin excretion rate (UAER) especially in the range of 20-200 micrograms min-1, termed microalbuminuria, has been proposed as a risk marker and predictor for cardiovascular disease in non-diabetic subjects. Thus it would be of importance to describe the distribution of UAER in the non-diabetic population. Among 1011 30-70-year-old subjects without diabetes mellitus or urinary tract infection, who were invited to participate in a population based epidemiological study, the albumin concentration was measured in an overnight urine sample. The measurement was performed by an ELISA method. The UAER was calculated in units of micrograms min-1 as urinary albumin concentration x urine volume/urine collection time. The distribution of UAER was positively skewed with a median value of 2.3 micrograms min-1 and a 5-95 interpercentile range of 0-11.0 micrograms min-1. The UAER held constant with age, but males had higher UAER than females, 2.6 (0-13.5) micrograms min-1 vs 2.2 (0-8.3) micrograms min-1; p < 0.005. The prevalence of microalbuminuria, defined as an UAER in the range of 15-150 micrograms min-1 in an overnight urine sample, was 3% (95% C.I. interval: 1.9-4.0). These findings suggest, that the level of UAER which might notify increased cardiovascular risk, is lower than in patients with diabetes mellitus, if it is considered to be of any clinical relevance.