Search

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m 2 and 60 mL/min/1.73 m 2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300 mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.

Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200 μg min(-1), and short-term BP variability (BPV), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential hypertensives with normal estimated glomerular filtration rate (>60 ml min(-1) per 1.73 m(2)), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) patients. ARV of 24-h systolic BP (SBP) was significantly higher in patients with MAU (9.8 (8.5-11.1) mm Hg) when compared with those without it (9.1 (8-10.2) mm Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (β=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, diabetes, serum uric acid, triglycerides, estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term BPV tested were not independently associated with MAU. Our results seem to suggest that in essential hypertension, short-term BPV, only when estimated by ARV of 24-h SBP, is independently associated with MAU.

The authors aimed to analyze the relationship between subclinical renal damage, defined as the presence of microalbuminuria or an estimated glomerular filtration rate (eGFR) between 30 mL/min/1.73 m(2) and 60 mL/min/1.73 m(2) and short-term blood pressure (BP) variability, assessed as average real variability (ARV), weighted standard deviation (SD) of 24-hour BP, and SD of daytime and nighttime BP. A total of 328 hypertensive patients underwent 24-hour ambulatory BP monitoring, 24-hour albumin excretion rate determination, and eGFR calculation using the Chronic Kidney Disease Epidemiology Collaboration equation. ARV of 24-hour systolic BP (SBP) was significantly higher in patients with subclinical renal damage (P=.001). This association held (P=.04) after adjustment for potential confounders. In patients with microalbuminuria, ARV of 24-hour SBP, weighted SD of 24-hour SBP, and SD of daytime SBP were also independently and inversely related to eGFR. These results seem to suggest that in essential hypertension, short-term BP variability is independently associated with early renal abnormalities., (© 2015 Wiley Periodicals, Inc.)

There is clear evidence that urinary albumin excretion levels, even below the cut-off values currently used to diagnose microalbuminuria, are associated with an increased risk of cardiovascular events. The relationships of microalbuminuria with a variety of risk factors, such as hypertension, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced cardiovascular risk conferred by microalbuminuria. Nonetheless, several studies showed that the association between microalbuminuria and cardiovascular disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between microalbuminuria and cardiovascular risk remain incompletely understood. The simple search for microalbuminuria in hypertensive patients may enable the clinician to better assess absolute cardiovascular risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard cardiovascular risk factors.

Our study was aimed to assess the clinical correlates of different degrees of renal dysfunction in a wide group of non-diabetic hypertensive patients, free from cardiovascular (CV) complications and known renal diseases, participating to the REDHY (REnal Dysfunction in HYpertension) study. A total of 1856 hypertensive subjects (mean age: 47+/-14 years), attending our hypertension centre, were evaluated. The glomerular filtration rate (GFR) was estimated by the simplified Modification of Diet in Renal Disease Study prediction equation. A 24-h urine sample was collected to determine albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg min(-1). We used the classification proposed by the US National Kidney Foundation's guidelines for chronic kidney disease (CKD) to define the stages of renal function impairment. In multiple logistic regression analysis, the probability of having stage 1 and stage 2 CKD was significantly higher in subjects with greater values of systolic blood pressure (SBP) and with larger waist circumference. SBP was also positively related to stage 3 CKD. Stage 3 and stages 4-5 CKD were inversely associated with waist circumference and directly associated with serum uric acid. Age was inversely related to stage 1 CKD and directly related to stage 3 CKD. The factors associated with milder forms of kidney dysfunction are, in part, different from those associated with more advanced stages of renal function impairment.

Background: It has not been fully elucidated whether microalbuminuria (MAU) and high-sensitivity C-reactive protein (hsCRP) are associated with aortic distensibility independently of each other. Our study was aimed to evaluate the independent relationships of urinary albumin excretion rate (AER) and hsCRP with aortic stiffness in hypertensive patients., Methods: We enrolled 140 untreated nondiabetic essential hypertensives (mean age: 48 +/- 12 years). In all subjects, 24-hour AER and plasma levels of hsCRP were determined by immunoenzymatic assay. MAU was defined as an AER of 20-200 microg/min. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV)., Results: Carotid-femoral PWV, adjusted for age and mean arterial pressure (MAP), was higher in subjects with MAU (n = 41) than in those without it (n = 99) (11.6 +/- 2.3 vs. 9.9 +/- 1.8 m/s; P < 0.001) and in subjects with hsCRP above the median value when compared to those with lower levels of hsCRP (10.8 +/- 2.1 vs. 10 +/- 2.1 m/s; P = 0.026). In multiple regression analysis, AER and hsCPR remained independent predictors of aortic stiffness (beta = 0.24; P < 0.001 and beta = 0.15; P = 0.03, respectively)., Conclusions: Our results suggest that in patients with essential hypertension, MAU and CRP are independently associated with an increased aortic stiffness.

Aims: We assessed the prevalence of kidney dysfunction evaluated by different methods to estimate glomerular filtration rate (GFR) in a wide group of nondiabetic hypertensive patients, without cardiovascular (CV) complications and without known renal disease, participating in the Renal Dysfunction in Hypertension (REDHY) study., Methods: A total of 1,856 hypertensive individuals (mean age 47 +/- 14 years; men 53%), free from diabetes mellitus and CV complications, and consecutively attending our outpatient hypertension center, were enrolled. Patients with a body mass index >35 (calculated as kg/m(2)) were excluded. The GFR was estimated by the creatinine clearance rate (CrCl), the simplified Modification of Diet in Renal Disease Study prediction equation (MDRD), the Cockcroft-Gault formula (CG) and the Mayo Clinic quadratic equation (Mayo). A 24-hour urine sample was collected to evaluate CrCl and albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg/min., Results: The prevalence of albuminuria was 23.4% (22.7% microalbuminuria and 0.7% macroalbuminuria). Mild renal dysfunction (defined as 24-hour AER >20 microg/min in presence of eGFR > or =60 ml/min per 1.73 m(2)) was found in a proportion of patients ranging from 20.3% using CrCl, to 18.4% using the MDRD equation. The prevalence of overt renal insufficiency (estimated GFR <60 ml/min per 1.73 m(2)) was higher when CrCl (10.8%) or the MDRD equation (10%) was used to estimate the GFR, instead of the CG (7.4%) or Mayo equation (5.4%) (p<0.0001)., Conclusions: Mild renal dysfunction and overt renal insufficiency are highly prevalent among subjects with nonmalignant arterial hypertension without CV complications. However, the prevalence of moderate-to-severe renal function impairment is strongly influenced by the method used to estimate the GFR.

We hypothesized that in essential hypertensive patients (EHs), plasma levels of pro-atherogenic adhesion molecules would be increased and related with urine albumin excretion (UAE). Thus, this study was aimed at evaluating biochemical markers of endothelial activation and their relationship with UAE in a group of patients with uncomplicated EH. In basal condition soluble forms of adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, as well as 24-h UAE were assayed. One hundred patients with essential hypertension and no diabetes or ultrasonographic evidence of atherosclerosis were included in the study. Seventy normotensive healthy subjects served as controls. EHs were first studied overall, than were divided into two subgroups: those with UAE > or =20 mcg/min MAUs and those with UAE <20 mcg/min (non-MAUs). ICAM-1 (P<0.001) and VCAM-1 (P<0.0001) plasma concentrations were higher in EHs than in controls. Microalbuminuric EHs had greater levels of adhesion molecules than non-MAUs (ICAM-1 P=0.04; VCAM-1 P=0.02, respectively). In EHs UAE was correlated with ICAM-1 (r=0.29, P=0.003), and VCAM-1 (r=0.30, P=0.002). These associations were confirmed in multiple regression models (P=0.02 for both ICAM-1 and VCAM-1) including, along with adhesion molecules, age, body mass index and blood pressures. Our findings show that in essential hypertension there is a very early activation of endothelial adhesion molecules favouring atherosclerosis.

Objectives: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness., Design: Cross-sectional study., Setting: Outpatient hypertension clinic., Subjects: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER., Results: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added., Conclusions: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.

Background/aims: To evaluate the influence of microalbuminuria (albumin excretion rate--AER) determination and echocardiography (ECHO) on cardiovascular risk stratification, initially performed according the 1999 WHO/ISH guidelines by using only routine diagnostic procedures with or without fundal examination., Methods: 312 essential hypertensives attending our institution were studied retrospectively. Cardiovascular risk was assessed in a semiquantitative way using four categories of absolute cardiovascular disease risk (low, medium, high and very high risk), as proposed by the 1999 WHO/ISH guidelines, on the basis of data on the average 10-year risk of cardiovascular events among participants in the Framingham Study., Results: Without the retinal data, estimating the level of global cardiovascular risk on the basis of routine work-up alone, 14% were classified as low-risk patients, 48% were as medium-risk, 20% as high-risk and 18% at very-high-risk patients. The combined use of AER and ECHO, in line with the newer ESH-ESC guidelines, determined a statistically significant reclassification of the hypertensive patients. Only 10% remained in the low-risk category, 28% were classified in the medium-, 42% in the high- and 20% in the very-high-risk classes. The overall percentage of patients that changed risk stratum (mostly shifting from the medium- to the high-risk class) was significantly different from the proportion of subjects reclassified after the addition of either microalbuminuria or echocardiography alone. No change in the distribution of risk categories was observed when AER assay and ECHO were added to routine procedures including funduscopic examination., Conclusions: Considering the questionable prognostic value of qualitative retinal examination, our results suggest that cardiovascular risk evaluation based only on simple routine work-up, ignoring the information provided by AER determination and ECHO, may underestimate the level of absolute risk., (Copyright 2004 S. Karger AG, Basel)

Both microalbuminuria (>0.290 nmol/min [20 microg/min]) and high sodium-lithium countertransport (SLC) in diabetic or hypertensive humans are predictive of overt nephropathy and more aggressive cardiovascular complications, perhaps induced by insulin resistance. To analyze the relationships between microalbuminuria, SLC, microalbuminuria, and insulin in essential hypertension, we studied 90 hypertensive white patients, 25 of whom had microalbuminuria and 32 of whom were healthy. When urine sampling was completed for albuminuria determination, SLC was measured; all patients then underwent standard (75 g) oral glucose load to measure basal (0 minutes) and 2-hour glucose and insulin serum levels. Glucose-insulin ratio was used as insulin sensitivity index (ISI). In both hypertensive patients with normal microalbuminuria and those with pathological microalbuminuria, plasma insulin at 120 minutes was significantly higher than in control subjects. When the patients with pathological microalbuminuria were divided into thirds on the basis of their microalbuminuria, in the lower third, we found statistically significant less fasting insulin and higher basal ISI. SLC was higher in hypertensives than normotensives and, among hypertensives, higher in the subgroup with elevated microalbuminuria. In hypertensives, we found a weak but significant correlation between SLC and microalbuminuria, independent of insulin or ISI. The prevalence of high value of SLC (> or =0.383 mmol x L-1 x h-1) was significantly lower in hypertensives with normal rather than abnormal urinary albumin excretion. Our results indicate that in nondiabetic hypertensive whites, higher microalbuminuria is accompanied by signs of insulin resistance; moreover, a link exists between SLC and microalbuminuria, both predictive of aggressive complications of hypertension.