Microalbuminuria In Hypertension Research Articles

Ayurvedic management for hypertension with micro albuminuria: a case report

Hypertension is a non-communicable disease in which the pressure of blood pushing against the arterial walls becomes high. In chronic stage it leads to severe systemic diseases, which affects heart, kidney, lung etc. The main causative factors are unhealthy food and lifestyle, stress, smoking, Alcohol, obesity and hereditary. Microalbuminuria in Hypertension is an early sign of kidney damage and is considered as a predictor for the end stage of renal disease and cardiovascular disease. So, it is of great importance to manage microalbuminuria or high urine albumin creatinine ratio and progression of kidney disease in hypertensive patient. In Ayurveda references no proper description of hypertension is available. By viewing the pathogenesis and physiology, it is formed by the involvement of Tridoshas, Srotorodha, and Dhatudushti. The present case is a 60-year male patient was diagnosed uncontrolled hypertension with microalbuminuria, admitted for 1month, presented with complaints such as frothy urine, over tiredness, uncontrolled anger and increased blood pressure during evening time, not controlled by hypertensive modern medicines. His urine albumin-creatinine ratio was 106.98 mg/dl of creatinine, microalbumin in urine 138 mg/dl and uric acid was 11.5 mg/dl. He was advised the internal Ayurveda medicines, diet restriction and yogic breathing exercise. Within one month of treatment the urine albumin creatinine ratio and uric acid was reduced and became normal. His blood pressure also became controlled and recovered all symptoms. Ayurvedic treatment module appears to be safe and efficacious with early recovery and better outcomes in this case.

Prevalence of Microalbuminuria and its Association with Left Ventricular Hypertrophy (LVH), Ischemic Heart Disease (IHD), Retinopathy, and Stroke in Hypertension

Background: Hypertension is a growing issue of public health problem of the adult population in both developed as well as developing world, is a serious medical condition that significantly increases the risks of heart, brain, kidney, and other diseases. There is a strong association between Microalbuminuria (MA) and hypertension. Microalbuminuria (MA) is the independent risk factor for developing cardiovascular and cerebrovascular morbidity and mortality in hypertension, suggesting that microalbuminuria (MA) could be a useful marker to assess the risk management of cardiovascular disease and renal disease.
 Objective: To assess the frequency of microalbuminuria in hypertension and to evaluate its association with left ventricular hypertrophy (LVH), ischemic heart disease (IHD), retinopathy, and stroke.
 Methods: This cross-sectional descriptive study was conducted at the Hypertension & Research Centre, Rangpur from January 2010 to January 2012. A total of 75 hypertensives without diabetes mellitus and/or other conditions causing microalbuminuria were purposively selected. Urine albumin was assessed and microalbuminuria was defined as albumin excretion between 20-200 microg/min. The relationship of microalbuminuria with the duration, severity, body mass index (BMI), lipid profile, and target organ damage (TOD) like left ventricular hypertrophy (LVH), ischemic heart disease (IHD), hypertensive retinopathy, and stroke was assessed by univariate analysis.
 Results: The patients were in between the age of 20-79 years with mean age of 52.98±12.2. Out of 75 subjects, 47 (62.7%) patients were male and 28 (37.3%) were female. Of the study group, 53 patients had stage 1 and 22 patients had stage 2 hypertension. Among the stage-1 hypertensive (53), 5 patients had microalbuminuria and 6 patients had microalbuminuria in stage-2 hypertensive (22) (p=0.047). Microalbuminuria was significantly higher in those with longer duration and greater severity of hypertension (p =0.039). Older age (p =0.008), and adverse lipid profile (p =0.003) were the other identifiable risk factors for microalbuminuria. Stroke (OR=9.77), echocardiography-proven LVH (OR=6.25), ECG and/or echocardiographyproven IHD (OR=8.71) and hypertensive retinopathy (OR=4.14) were significantly higher in those with microalbuminuria.
 Conclusion: The prevalence of microalbuminuria in hypertensive subjects is high and patients with microalbuminuria have high odds of developing TOD like stroke, LVH, IHD, and hypertensive retinopathy. So the early detection of microalbuminuria in hypertensive as well as prompt treatment may reduce the burden of TOD.
 J Rang Med Col. March 2023; Vol. 8, No. 2:3-10

Microalbuminuria in hypertension and its relationship to target organ damage: A cross-sectional observational study in a tertiary hospital in Eastern India

Background: Microalbuminuria (MA) is an independent risk factor in association with fatal cardiovascular and cerebrovascular outcomes among patients with hypertension (HTN). Methods: An observational study was conducted among 100 randomly selected hypertensive patients January 2013 to January 2014 to observe the proportion of MA among hypertensive patients and the proportion of presence of various target organ damages (TODs) in them. Results: The frequency of MA was 36% among participants. The frequency in males was slightly more than females (38.2% vs. 33.3%). The frequency of MA increased linearly with the duration and severity of HTN. It was more commonly found in smokers than in non-smokers. Diastolic dysfunction (42%) and Grade 2 hypertensive retinopathy (60.7%) were associated with MA. TOD was frequently observed in MA-positive patients. Conclusions: The proportion of patients with MA was in increasing trend with increasing age of hypertensive participants and duration of history of HTN. Hypertensive retinopathy, regional wall motion abnormality and neurological deficit emerged to be sensitive surrogate markers for MA in patients with HTN.

Frequency of Microalbuminuria in Essential Hypertension and type II Diabetes Mellitus in Tertiary Care Hospital

Introduction: Hypertension is the growing issues of public health problem of adult population in both developed as well as developing world, affecting single person in every four people. Objectives: The main objective of the study is to find the frequency of microalbuminuria in essential hypertension in tertiary care hospitals. Material and Methods: This Randomized Control Trial was conducted in DHQ hospital Sahiwal during 2020 to 2021. Blood sample of all the patients diagnosed with microalbuminuria in hypertension presented to the hospital were taken and sent to laboratory for performing fasting blood glucose and 1st morning Urine sample was taken and analyzed for albumin to creatinine ratio of these patients. Results: The age range of patients in this research was from 18-75 years. The mean age of patients was 40.35 ± 8.65 years. In group A the mean age of patients was 39.60 ± 10.12 years and in group B was 41.0 ± 8.05 years. Conclusion: This study concluded that efficacy of losartan is higher than lisinopril for reduction of microalbuminuria in patients with type-2 diabetes mellitus. Keywords: type II diabetes, microalbuminuria, losartan.

Relationship Between Resting Heart Rate and Microalbuminuria in Adults With Hypertension: National Health and Nutrition Examination Survey 2009-2018.

BackgroundThe impact of elevated resting heart rate on early-stage renal dysfunction, manifesting as microalbuminuria, in hypertension is unclear. This study aimed to analyze the association between resting heart rate and microalbuminuria in patients with hypertension according to their blood pressure status. In addition, the effect of antihypertensive agents on this relationship was evaluated.Methods and ResultsWe searched the National Health and Nutrition Examination Survey for eligible participants from 2009 to 2018. Data on key parameters such as age, sex, blood pressure, heart rate, albumin creatinine ratio, and medication were collected for analysis. Subsequently, participants were classified according to the heart rate quartile and blood pressure status for subgroups assessment. A total of 5,692 participants were enrolled in this study. After adjusting the confounding factors, there was a linear association between resting heart rate and microalbuminuria in patients with hypertension (OR 1.184 [per 1 SD]; 95% CI: 1.101, 1.274; P < 0.001). However, the association between elevated resting heart rate and microalbuminuria was not significant in patients with uncontrolled hypertension (OR 1.092 [per 1 SD]; 95% CI: 0.935, 1.275; P = 0.269). The OR of the indirect effect of β-blockers on the risk of microalbuminuria incidence through heart rate was 0.926 (95% CI: 0.895, 0.956), while the direct effect was 1.374 (95% CI: 1.138, 1.662, P = 0.010). Similarly, dihydropyridine calcium channel blockers were associated with a higher prevalence of microalbuminuria (OR 1.300, 95% CI: 1.058, 1.597, P = 0.013), but the association between non-dihydropyridine calcium channel blockers and microalbuminuria was not significant (OR 1.207, 95% CI: 0.737, 1.978, P = 0.454).ConclusionElevated resting heart rate is associated with a high risk of microalbuminuria in untreated patients and patients with controlled hypertension. Although there is a linear association between heart rate and microalbuminuria, the use of β-blockers exhibits a significantly increase in the prevalence of microalbuminuria in hypertension. Likewise, dihydropyridine calcium channel blockers may increase the risk of microalbuminuria in hypertension.

Study on microalbuminuria as predictor factor for target organ damage in essential hypertension in a teaching hospital, Telangana

Background: Microalbuminuria in hypertensives is related to future development of cardiovascular morbidity. It is a simple test which is easily available. In the present study we attempted to look at the prevalence of microalbuminuria in cases of essential hypertension and also to determine its association with left ventricular hypertrophy and carotid intima-media thickness and retinopathy. Aim of the study: To study microalbuminuria as a predictor factor for target organ damage in essential hypertension. Materials and Methods: Hospital based prospective observational study done on 45 cases for duration of one year. Cases of essential hypertension were studied for microalbuminuria, for changes of left ventricular hypertrophy, left ventricular mass index distribution and for retinopathy. Results: There was a slight male predominance and the M:F ratio was 2.7:1. Majority of cases were among 40-50 years age group ie, 62.2% cases. Microalbuminuria was present in 77.7% cases. ECG changes of left ventricular hypertrophy were present in 77.7% cases. Obesity and over weight were present in 15 (33.3%) subjects. Among 35 cases with microalbuminuria, 19 patients had hypertensive retinopathy changes. Among these 19 patients, Grade II retinopathy was most common and was diagnosed in 68.4% cases. Conclusion: Microalbuminuria is common in patients with essential hypertension. Microalbuminuria can predict cardiovascular and ocular morbidity in the form of left ventricular hypertrophy, increased carotid intima-media thickness; and ocular morbidity respectively. Screening of all patients with essential hypertension will help to predict the future risk for target organ damage. Keywords: Microalbuminuria, Essential Hypertension, Left ventricular hypertrophy.

EXOSOMAL MICRORNA PROFILE IN HYPERTENSIVE PATIENTS WITH ALBUMINURIA

Objective: Urinary albumin excretion (UAE) is an indicator of early renal and cardiovascular damage. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and changes in the miRNA levels in biofluids have been related to several pathophysiological conditions. Recently, exosomes (small membranous vesicles of 40–130 nm) have been described as new biological effectors able to transport nucleic acids, proteins and lipids between cells. The aim of this work was to identify the exosomal miRNAs associated to the presence of albuminuria in hypertension. Design and method: This prospective study analyzed 52 hypertensive patients, 24 with microalbuminuria (UAE = 162,8 ± 168.2 mg/g creatinine; mean age 52.7 ± 8.4 years) and 28 normoalbuminuric (mean age 54.5 ± 5.6 years). Exosomes were isolated by differential ultracentrifugation from urine and plasma. After RNA isolation, we prepared individual libraries for small RNAs and sequence them by next-generation sequencing. MiRNA over-representation and enrichment analysis were performed in order to identify the most regulated biological processes (KEGG pathway database). Validation was performed by RT-qPCR and miR-26a-5p levels were correlated to UAE. Results: We found a signature of 29 exosomal miRNAs differentially expressed in response to microalbuminuria. The most regulated biological processes by the miRNAs obtained were cell signaling (MAPK, calcium, p53), TGF-beta and VEGF pathways, cytokine-cytokine receptors, regulation of actin cytoskeleton, cell cycle and apoptosis, cell junctions and extracellular matrix molecules and interactions. Particularly, only miR-26a-5p was found altered (down-regulated, 4-fold change) in both urine and plasma exosomes. We validated a decrease in the levels of miR-26–5p in urinary exosomes of microalbuminuric patients (4.7- fold change, p < 0.05). Finally, miR-26a-5p copy number correlated inversely with UAE levels (r = −0.546, p < 0.05). Conclusions: Our results show an exosomal miRNA signature associated to microalbuminuria in hypertension. Interestingly, miR-26a-5p is decreased in urinary exosomes of microalbuminuric patients. This miRNA appears to be regulating VEGF and TGF-beta, key molecules in the development and maintenance of glomerular filtration barrier. The identified miRNAs may shed new light on how albuminuria develops and progress in hypertension.

Prevalence of microalbuminuria in hypertension monitored in primary care

The objectives of the study were to evaluate the prevalence of microalbuminuria (MAU) in patients with hypertension, monitored in primary care and to analyse the correlation between MAU, risk factors and associated parameters. Material and methods. During 2010-2014 we evaluated a number of 910 patients from 19 family medicine offices of Timiş County. The general practitioners took a standardized history, performed a physical examination, measured height, weight, blood pressure, ABPM and heart rate, calculated body mass index and tested urine for MAU with Arkray test strips. The patients with hypertension and MAU were referred to diagnosis centres where they underwent echocardiography. Results. After exclusion of patients with a history of renal disease and diabetes, MAU was present in 61 cases, 7.1%. The mean age of the MAU positive patients was 56±13.1 years, ranging from 29 to 79. The duration of hypertension was under 5 years in 4 (2.44%) patients, between 5-10 years in 35 (57.3%) and over 10 years in 22 (36%) Six patients with MAU (9.83%) had mild hypertension, 25 (40.9%) moderate and 30 (49.1%) severe hypertension. LVMI was 125 ± 28 g/m2 in the MAU absent group and 157 ± 56 g/m2 in the MAU present group (&lt;0.04). A stepwise logistic regression analysis showed significant positive effects of 24 h systolic blood pressure, weight and LVH (p&lt;0.001 for all comparisons) on MAU. No other variable had a significant predictive effect on the presence or absence of MAU. Conclusions. In patients with essential hypertension MAU was present in 7.1%, with a higher prevalence in uncontrolled than in controlled hypertension. MAU was associated with high blood pressure levels, obesity and LVH.

Abstract 451: Central Hemodynamics Constitutes the Link Between Microalbuminuria and Elevated B-type Natriuretic Peptide Level: Implication for Cardio-renal Syndrome in Hypertension

Recent research has noted a pathological link between the heart and kidney, known as cardio-renal syndrome. However, little is clear about the pathophysiological mechanism behind it. A relationship of altered central hemodynamics to microalbuminuria in hypertension has been demonstrated ( Hypertension 2011;58:839-846). The present study was conducted to investigate two hypotheses: 1) a link between albuminuria and plasma B-type natriuretic peptide (BNP); and 2) involvement of central hemodynamics in this link. In 392 patients with uncomplicated hypertension (age, 56±12 years), the radial pressure waveforms were recorded with applanation tonometry to estimate the central aortic pressure parameters. The pulse wave velocity (PWV) was measured in carotid-femoral (aortic) and carotid-radial (peripheral) regions. Albuminuria was defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g of creatinine. The log-transformed BNP (median, 14 pg/ml) was correlated ( P ≤0.006) with aortic systolic ( r =0.31) and pulse ( r =0.46) pressures, aortic forward ( r =0.41) and augmented ( r =0.26) pressures, mean arterial pressure ( r =0.14), and aortic ( r =0.39) but not peripheral ( r =–0.09) PWV. The correlation with the aortic pulse pressure tended to be closer than the brachial pulse pressure ( P =0.07). The BNP was correlated ( P &lt;0.001) positively with UACR ( r =0.34), and negatively with estimated glomerular filtration rate (eGFR, r =–0.39). The presence of albuminuria was associated with an elevation of BNP (≥40 pg/ml) in a stepwise logistic model adjusted for age, body mass index, diabetes, eGFR, use of renin-angiotensin inhibitors and β-blockers (odds ratio: 2.74; P =0.007). Of note, however, additional adjustment for the aortic pulse pressure rendered this association statistically insignificant, and the aortic pulse pressure emerged as the strongest predictor of the BNP elevation (odds ratio: 1.41 per 10mmHg increase; P =0.003). In each patient subgroup with normo-, micro-, and macro-albuminuria, wider aortic pulse pressure was always associated with higher BNP level. In conclusion, albuminuria and elevated BNP are closely connected in hypertension. The central hemodynamics plays a pivotal role in mediating this cardio-renal connection.

Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension.

Background In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.

Relationship between GFR and albuminuria in stage 1 hypertension.

Whether glomerular hyperfiltration is implicated in the development of microalbuminuria in hypertension is not well known. This prospective study investigated the relationship between changes in GFR and microalbuminuria in hypertension. This study assessed 534 stage 1 hypertensive participants from the Hypertension and Ambulatory Recording Venetia Study (n=386 men) without microalbuminuria at baseline, who were recruited from 1990 to 1995 and followed for a median of 8.5 years. Mean age was 33.9±8.6 years and mean BP was 146.6±10.5/94.0±5.0 mmHg. Creatinine clearance and 24-hour urinary albumin were measured at study entry and end. Participants were defined as normofilterers (normo) or hyperfilterers (hyper) according to whether GFR was <150 or ≥150 ml/min per 1.73 m(2), respectively. Participants were divided into four groups based on GFR changes from baseline to follow-up end: normo→normo (n=395), normo→hyper (n=31), hyper→hyper (n=61), and hyper→normo (n=47). Microalbuminuria progressively increased across the four groups and was 5.3% in normo→normo, 9.7% in normo→hyper, 16.4% in hyper→hyper, and 36.2% in hyper→normo (P<0.001). This association held true in a multivariable logistic regression in which several confounders, ambulatory BP, and other risk factors were taken into account (P<0.001). In particular, hyperfilterers whose GFR decreased to normal at study end had an adjusted odds ratio of 7.8 (95% confidence interval, 3.3-18.2) for development of microalbuminuria compared with participants with normal GFR throughout the study. These data support the hypothesis for a parabolic association between GFR and urinary albumin in the early stage of hypertension.

Prevalence and Association of Microalbuminuria in Essential Hypertensive Patients

Background:Microalbuminuria in hypertension has been described as an early sign of kidney damage and a predictor for end stage renal disease and cardiovascular disease. Thus, it is of great importance to study urinary albumin creatinine ratio and progression of kidney disease in hypertensive patients.Aims:The present study was undertaken to find out the prevalence and association of microalbuminuria in newly diagnosed essential hypertension.Materials and Methods:Newly diagnosed essential hypertensive cases (n = 106) and normotensive controls (n = 106) were enrolled. Hypertension was defined according to Joint national committee-VII definitions. Microalbuminuria was measured using an U-Albumin (NycoCard, Norway) and adjusted for urine creatinine. Descriptive statistics and testing of hypothesis were used for the analysis using SPSS 16 software.Results:51.88% of hypertension cases and 13.2% of normotensive controls had microalbuminuria in total population (odds ratio 7.086, P-value <0.001). 46.67% of cases and 12.08% of controls had microalbuminuria in male population (odds ratio 6.375, P-value <0.001). Similarly, 58.7% of cases and 14.58% of controls had microalbuminuria in female population (odds ratio 8.32, P-value <0.001).Conclusions:By showing strong association between microalbuminuria and hypertension, our findings suggest that microalbuminuria could be a useful marker to assess risk management of cardiovascular disease and renal disease.

The Different Concentrations of Transforming Growth Factor-Beta1 (TGF-Beta1), Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) in Normoalbuminuria Normotension, Normoalbuminuria Hypertension

BACKGROUND: Vascular remodeling was an adaptive process of the vascular wall that occured in response to long-term changes in hemodynamic conditions that contribute to the changes of the vascular structure and the pathophysiology of vascular disease. On the other hand, Endothelial Progenitor Cells (EPC) derived from bone marrow had the capacity to migrate to the peripheral circulation and to differentiate into mature endothelial cells. Therefore, EPC could contribute in the endothelial repairing after endothelial injury.METHODS: This study was a cross sectional design. Analysis was done among 30 subjects with normoalbuminuria normotension, 55 subjects with normoalbuminuria hypertension and 30 subjects with with microalbuminuria hypertension. TGF-β1, MMP-9 and VEGFR-2 testing were performed by ELISA method. All statistical calculations were performed using the SPSS 11.5 statistical software package. We used the Independent sample T test, Mann-Whitney, One Way Annova and Kruskal Wallis to establish the difference among various biochemical measures.RESULTS: TGF-β1 concentration was increased from normoalbuminuria normotension to normoalbuminuria hypertension and to microalbuminuria hypertension (27.63178±12.97246 vs. 38.61193±17.09546 vs. 38.73939±12.63911 ng/mL). TGF-β1 concentration was higher significantly in normotension as compared to hypertension (27.63178±12.97246 vs. 38.65692±15.58950, p&lt;0.001) and to microalbuminuria hypertension (38.73939±12.63911, p&lt;0.001). MMP-9 concentration was increased in normotension to normoalbuminuria hypertension but was decreased in microalbuminuria hypertension (438.1967±156.4268 vs. 564.5873±291.2876 vs. 418.6900±188.3801 ng/mL). MMP-9 concentration was higher significantly in normoalbuminuria hypertension as compared to microalbuminuria hypertension (p=0.028). VEGFR-2 concentration was decreased from normotension to normoalbuminuria hypertension to microalbuminuria hypertension (9.90552±1.85185 vs. 9.39561±1.75413 vs. 9.00506±1.47173 ng/mL). VEGFR-2 concentration was higher significantly in normotension as compared to microalbuminuria hypertension (p=0.042). CONCLUSIONS: The increasing concentration level of TGF-β1 and decreasing concentration level of MMP-9 in microalbuminuria hypertension showed that the remodeling process was getting increased. The decreasing concentration level of VEGFR-2 in microalbuminuria hypertension showed that the repairing process was getting decreased.KEYWORDS: vascular remodelling, vascular repairing, TGF-β1, MMP-9, VEGFR-2

Cystatin C as Predictor of Microalbuminuria in the Early Stage of Hypertension

Background/Aims: Predictors of microalbuminuria in the early stage of hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration assessed from serum cystatin C predicts development of microalbuminuria in hypertension. Methods: We assessed 101 treatment-naive subjects screened for stage 1 hypertension and followed-up for a median 3.1 years. Cystatin C was measured at entry and glomerular filtration rate was estimated using the Hoek formula (CystGFR). Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up. Results: Subjects in the top CystGFR tertile (>115 ml/min/1.73m²) were leaner (p = 0.002) and developed microalbuminuria more frequently (p = 0.02) than the rest of the group. In univariate Cox regression, CystGFR was associated with future microalbuminuria (hazard ratio, 1.06, 95% confidence interval (CI), 1.02–1.10, p = 0.001). After controlling for baseline albumin excretion rate and several confounders, CystGFR remained a significant predictor of microalbuminuria development (hazard ratio, 1.19, 95% CI, 1.03–1.37, p = 0.019). The association between future microalbuminuria and creatinine clearance or glomerular filtration rate estimated with the Cockroft-Gault or the Modification of Diet in Renal Disease formula did not attain the level of statistical significance in this sample. Conclusions: The present findings indicate that CystGFR is more sensitive than creatinine clearance or estimated glomerular filtration rate for predicting microalbuminuria development in the early stage of hypertension and confirm that hyperfiltration precedes microalbuminuria in this clinical entity.

Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: The HARVEST

Factors related to the development of microalbuminuria in hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration precedes the development of microalbuminuria in hypertension. We assessed 502 never-treated subjects screened for stage 1 hypertension without microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance was measured at entry. Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up until subjects developed sustained hypertension needing antihypertensive treatment. Subjects with hyperfiltration (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were younger and heavier than the rest of the group and had a greater follow-up increase in urinary albumin than subjects with normal filtration (P<0.001). In multivariable linear regression, creatinine clearance adjusted for confounders was a strong independent predictor of final urinary albumin (P<0.001). In multivariable Cox regression, patients with hyperfiltration had an adjusted hazard ratio for the development of microalbuminuria based on at least one positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and an adjusted hazard ratio for the development of microalbuminuria based on two consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared with patients with normal filtration. Age, female gender, and 24 h systolic blood pressure were other significant predictors of microalbuminuria. In conclusion, stage 1 hypertensive subjects with glomerular hyperfiltration are at increased risk of developing microalbuminuria. Early intervention with medical therapy may be beneficial in these subjects even if their blood pressure falls below normal limits during follow-up.

α-Adducin and angiotensin-converting enzyme polymorphisms in hypertension: evidence for a joint influence on albuminuria

A single-nucleotide polymorphism (Gly460Trp) within the alpha-adducin gene (ADD1) may influence several renal phenotypes, including salt sensitivity, susceptibility to renal failure, the renal haemodynamics and confer a worse cardiovascular risks profile. However, its relationship with microalbuminuria, a marker of early renal and cardiovascular damage and an independent predictor of morbid events in hypertension, is unknown. For this reason, we related the ADD1 genetic polymorphism to urine albumin levels and other clinical variables in essential hypertensive men. The angiotensin-converting enzyme (ACE) insertion/deletion (ID) polymorphism was also evaluated because of its interactive potential with the ADD1 genotype. Albuminuria (three overnight collections), echocardiographic left ventricular mass index, blood pressure, body mass index, renal function, glucose and lipids were measured in 238 genetically unrelated, never treated, uncomplicated Caucasian essential hypertensive men. Polymerase chain reaction or a 5' nuclease assay were used to characterize the ACE ID and ADD1 Gly460Trp variants, respectively. Microalbuminuria (albuminuria >or= 15 microg/min) was more frequent in patients with the ACE DD variant, but only in those with a ADD1 Gly460Gly background. In contrast, urine albumin did not differ by ACE ID genotype in the presence of mutated ADD1 Trp alleles. ADD1 polymorphisms per se were not associated with albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed among different genetic backgrounds. ACE DD and ADD1 Gly460Gly polymorphisms may jointly influence albuminuria in hypertensive men, 460Gly homozygosis facilitating or, possibly, the 460Trp allele mitigating the noxious renal impact of the ACE DD genotype. The data highlight further the complex pathophysiological implications of microalbuminuria in hypertension.

Microalbuminuria

Microalbuminuria

Is it time to measure microalbuminuria in hypertension?

Former guidelines on hypertension never made a commitment to the detection of microalbuminuria for screening or follow-up of hypertensive patients. On the other hand, growing evidence support the contributory role of microalbuminuria in the prediction of absolute cardiovascular risk in hypertension and document the potential relevance of this parameter to the initial choice of antihypertensive treatment. Upcoming new guidelines and diagnostic algorithms in hypertension need to underscore the clinical positioning of microalbuminuria for stratification of risk and follow-up purposes.

Microalbuminuria in hypertension.

A body of evidence indicates that microalbuminuria is a well-recognized marker of cardiovascular complications and increased cardiovascular risk in hypertension. However, the prognostic significance of microalbuminuria remains controversial because only the results of a few prospective studies performed in small groups of hypertensive subjects without diabetes mellitus are available. Several factors can affect the prevalence of microalbuminuria in hypertension including age, sex, race, severity of the disease, and concomitant risk factors. This accounts for the large differences in the prevalence of microalbuminuria that can be found in the literature, with prevalence rates going from a low of 4.7% to a high of 46%. The main determinant of albumin excretion rate in subjects with mild hypertension and no cardiovascular complications seems to be the hemodynamic load, whereas in subjects with more severe hypertension and associated target organ damage, the augmented urinary albumin leak is probably the consequence of glomerular damage. Inhibition of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists is particularly effective at reducing the albumin excretion rate, but whether these classes of drugs are more beneficial in patients with microalbuminuria remains to be determined. There is general consensus that evaluation of microalbuminuria is useful for the assessment of overall cardiovascular risk in hypertension, since albumin excretion rate appears to be a cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.

Microalbuminuria in hypertensives is related with blood pressure variability measured by 24-hour blood pressure standard deviation

In hypertensives 24-h BP standard deviation (24-h BP S.D., measuring BP variability) has been related to organ damage progression independently on 24-h mean BP. In hypertensives, microalbuminuria (MA) measured after antihypertensive treatment have a particularly high prognostic value for cardiovascular-renal deterioration. We studied the relationship between 24-h BP S.D or the index of variation (InV = 24-h BP S.D/square root of average BP) and MA and/or aortic pulse wave velocity (PWV - Complior) in 198 hypertensive patients with an urinary excretion of albumine between 5 and 300 mg/24h after stable antihypertensive medication for > 4 months: 135 were type 2 diabetics (DM), ageing 61 (2), 72 male and 63 were non diabetics (non DM) ageing 60 (2), 32 male. Both index of variation and 24-h BP S.D significantly correlated with albuminuria either in DM (r=0.354, p<0.001) and non DM (r=0.302, p<0.01). In the 1srt, 2nd and 3rd tertiles of distribution of index of variation, there was a significant (p<0.04) trend for albuminuria 37(5), 51(6) and 78 (6) mg/24h and for PWV 12.0 (0.2), 12.7(0.3) and 13.8 (0.2) m/s but not for mean 24-SBP 136(2), 137(2) and 136 (2) mm Hg. For similar age, sex, weight and 24-h BP S.D., in 116 patients on ACEinhibitors or angiotensin receptor blockers based regimens versus 72 patients on other antihypertensive regimens, similar albuminuria levels i.e. 51 (7) v 63 (6) mg/24h, PWV i.e. 12.8 (0.2) v 12.9 (0.2) and 24-h SBP i.e. 137 (2) v 135 (2) mm Hg were observed (all p>0.7). We conclude that in both DM and non-DM hypertensives the 24-h BP variability achieved after antihypertensive treatment may be an important determinant of microalbuminuria level independently of the type of antihypertensive regimens.