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Purpose: To assess the relation between retinal vascular caliber and renal function., Patients and Methods: Eighty apparently healthy subjects screened for cardiovascular risk factors (mean age 47 years, 51% female, 36% hypertensive, without diabetes or renal dysfunction) were recruited. Retinal vascular calibers were measured from fundus photographs and expressed as central retinal artery and venular equivalent. Renal function was assessed by measurement of glomerular filtration rate (urinary clearance of 99mTc-DTPA) and urinary albumin/creatinine ratio., Results: Mean glomerular filtration rate was 117 ml/min/1.73m(2). Overall, central retinal artery and venular equivalent were positively correlated with glomerular filtration rate (r = +0.31, p = 0.005 and r = +0.30, p = 0.006, respectively). In addition, central retinal artery equivalent was negatively correlated with urinary albumin/creatinine ratio (r = -0.34, p = 0.002). No significant relationship was found between central retinal venular equivalent and urinary albumin/creatinine ratio (r = +0.12, p = 0.32). The observed relations between retinal vascular calibers and renal function parameters remained significant after adjusting for potential confounding factors., Conclusion: In apparently healthy subjects with normal renal function, retinal arteriolar and venular calibers were negatively correlated with kidney function, suggesting common determinants of these preclinical target organ damages., (© 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.)

Background: In large epidemiological studies and using serum creatinine or estimates of glomerular filtration rate (GFR), blood pressure has emerged as a predominant determinant of the age-associated decline in renal function., Methods: The present longitudinal study (median follow-up period of 5.8 years) was conducted in 132 never-treated patients with essential hypertension at baseline. The effect of treatment on the GFR and effective renal plasma flow, estimated by urinary clearances of isotopic markers, was assessed., Results: Satisfactory control of hypertension (<140/90 mmHg) was achieved in 57% of the population. During follow-up, the yearly change in the GFR was -1.72+/-0.21 ml/min per year (mean+/-SEM). In univariate regression analysis, the change in the GFR was correlated with baseline pulse pressure (r=-0.27, P=0.002), whereas no influence of systolic, diastolic or mean blood pressures, as well as baseline albuminuria or left ventricular mass index, was found. Multivariate logistic regression analysis showed that only baseline pulse pressure conveyed a significant odds ratio of accelerated decline of GFR (>median of 1.5 ml/min per year), independently of age, baseline GFR, mean blood pressure and other known cardiovascular risk factors. No influence of the type of antihypertensive treatment (64% of the population had received angiotensin-converting enzyme inhibitor) was detected., Conclusion: Pulse pressure (a marker of arterial stiffening) is suggested as an independent determinant of the treatment-associated decline in renal function in essential hypertension. No influence of target organ damage (albuminuria of left ventricular hypertrophy) was detected.

Background: In the present longitudinal study, we attempted to identify the determinants of cardiorenal damage progression in normotensive subjects (<140/90 mm Hg) and patients with never-treated essential hypertension., Methods: Renal hemodynamics and function and cardiac morphology were evaluated by isotopic techniques and echocardiography at baseline and after a median follow-up period of 5.2 years (range 3 to 13) in 30 normotensive and 33 hypertensive subjects., Results: The results are mean +/- SD. Among normotensive subjects at baseline, 50% became hypertensive during follow-up. In the whole population, multivariate analysis showed that age was the main determinant of the progression of systolic blood pressure. The yearly change in glomerular filtration rate (GFR) was exaggerated in hypertensive when compared to normotensive subjects at baseline (-1.22 +/- 2.71 vs. 0.12 +/- 2.08 mL/min/year, respectively) (P= 0.033). In the whole population, only baseline systolic blood pressure remained correlated to the change in GFR, independently of GFR at baseline (model r(2)= 0.44) (P < 0.0001). The observed increase in albuminuria was correlated with change in blood pressure only in hypertensive subjects at baseline. Left ventricular mass (LVM) progression was significant only in men and its determinants were basal plasma aldosterone, serum uric acid, and triglyceride and change in systolic blood pressure (r(2)= 0.71) (P < 0.0001)., Conclusion: In a population of untreated subjects, baseline blood pressure as well as progression of blood pressure during follow-up are the main determinants of the decline in GFR, progression of albuminuria, and LVM.

In the past decade, pulse pressure has emerged as a strong predictor of cardiovascular morbidity and mortality. During aging, elevation of pulse pressure is a consequence of stiffening of the arterial wall. The relationship between pulse pressure and the renal aging process was studied in a cohort of 212 patients with never-treated isolated systolic hypertension. Glomerular filtration rate and effective renal plasma flow were measured using constant infusion of technetium 99m (99mTc)-DTPA and 131I-ortho-iodohippurate, respectively, and timed urine collections. The relationship between pulse pressure and renal function was studied using a linear regression model in the total population and in 40 to 49, 50 to 59, and 60 years and older age categories. In the whole population, there was an inverse relationship between pulse pressure and glomerular filtration rate; however, this relation did not persist after adjustment for age. In fact, the inverse relationship between pulse pressure and glomerular filtration rate was only present in patients 60 years of age or older. This relationship in elderly patients remained after adjustment for age, gender, MAP, and cardiovascular risk factors (P=0.006). It is suggested that pulse pressure, a marker of arterial stiffening, may have a detrimental influence on the age-related decline in glomerular filtration rate, after 60 years of age in patients with never-treated isolated systolic hypertension.

Blood pressure is a marker of elevated risk for cardiovascular disease, even within the normotensive range. The present study evaluates cardiorenal modifications observed in normotensive (<140/90 mm Hg) subjects. Using World Health Organization-International Society of Hypertension definitions, 265 normotensive subjects were categorized as having optimal (n=73), normal (n=84), and high-normal (n=108) blood pressure. Renal hemodynamics and function and cardiac morphology were evaluated by isotopic clearance techniques and ultrasonography, respectively. Urinary albumin excretion was measured in 24-hour urine collections. Body mass index and 24-hour urinary sodium (estimate of sodium intake), as well as left ventricular mass index, relative wall thickness, and glomerular filtration rate and filtration fraction, progressively increased in the optimal to high-normal groups. In contrast, effective renal plasma flow remained constant. Albuminuria was similar in all groups. Of interest, the proportion of subjects with concentric pattern of cardiac geometry (relative wall thickness > or =0.44) increased from 7% in optimal to 13% and 20% in normal and high-normal groups, respectively (P<0.05). Within this normotensive range of blood pressure, left ventricular mass index and relative wall thickness but not albuminuria were linearly correlated to systolic blood pressure; however, no correlation with diastolic blood pressure was found. In conclusion, changes in cardiac geometry and renal hemodynamics (increase in glomerular filtration rate and filtration fraction, an approximate index of glomerular pressure) that could predispose to cardiovascular morbidity and renal risk are already present in normotensive subjects with blood pressure higher than 120/80 mm Hg.

In the general population, renal function linearly declines with age; hypertension may accelerate this decline. Because concentric left ventricular (LV) hypertrophy is a strong marker of the severity of hypertension, the influence of LV geometry on the age-associated decline in renal function was assessed in 195 normotensive subjects and 645 patients with never-treated essential hypertension with an average duration of 30 mo. According to LV mass and relative wall thickness, hypertensive patients were divided into normal LV (NL, 48%), concentric remodeling (CR, 19%), and concentric (CH, 22%) and eccentric (EH, 11%) hypertrophy. GFR and effective renal plasma flow (ERPF) were estimated by isotopic clearance technique. GFR and ERPF were inversely correlated with age in normotensive and hypertensive subjects, and no marked influence of the BP level or the presence of LV hypertrophy was detected. However, the slope of the regression line of GFR versus age was accentuated (P < 0.01) in patients with CH or CR (slope values of -0.95 +/- 0.11, -0.86 +/- 0.14 ml/min per yr, respectively) when compared with patients with EH or NL (slope values of -0.58 +/- 0.16 and -0.58 +/- 0.08 ml/min per yr, respectively). No such results were obtained when creatinine clearance was considered. Urinary albumin excretion was higher in patients with concentric or eccentric LV hypertrophy than in patients with concentric LV remodeling or normal LV. These results demonstrate that in never-treated essential hypertension, the age-associated decline in GFR is markedly influenced by the concentric pattern of LV response to hypertension rather than the level of BP and/or the presence of LV hypertrophy.

Background: Renal function is thought to decrease with age in the general population, but the determinants of this age-associated evolution are poorly understood. Hypertension and diabetes mellitus, two leading causes of chronic renal failure in the elderly, may accelerate this decline., Patients and Methods: Urinary clearances of [99mTc]diethylene triaminopentaacetic acid (DTPA) (glomerular filtration rate) and [131I]hippuran (effective renal plasma flow) were assessed in 227 never-treated essential hypertensives aged 20-69 years. Based on the oral glucose tolerance test, the study population consisted of 4% patients with previously unknown diabetes mellitus, 24% with impaired glucose tolerance and 72% with normal glucose tolerance., Results: When the population of 218 non-diabetic subjects was considered, glomerular filtration rate was inversely correlated with age and arterial blood pressure, and positively correlated with effective renal plasma flow, filtration fraction and fasting plasma glucose. In multivariate analysis, age and blood pressure were independent determinants of renal plasma flow, whereas renal plasma flow, age and fasting plasma glucose were independent determinants of glomerular filtration rate. The slope of the regression line relating glomerular filtration rate to age was steeper in patients with impaired glucose tolerance than in those with normal glucose tolerance (-1.52 +/- 0.28 versus -0.65 +/- 0.12, P < 0.01)., Conclusions: These results suggest that impaired glucose tolerance, which is seldom searched for in patients with essential hypertension, may be an important determinant of the age-associated decline in renal function.

-The determinants of the increase in arterial blood pressure associated with the use of estrogen-progestogen oral contraceptives (OC) remain poorly known. The purpose of this study was to assess the renal characteristics and the role of the renin-angiotensin system in women with OC-associated hypertension. Urinary clearances of technetium-labeled diethylene triaminopentaacetic acid (glomerular filtration rate) and 131I-ortho iodohippurate (effective renal plasma flow) were estimated before and after acute administration of captopril in 38 women who became hypertensive while taking OC, 38 non-OC users with essential hypertension matched for age, body mass index, and level of blood pressure, and 38 normotensive women (19 with and 19 without OC). Plasma renin activity was higher in OC hypertensives when compared with those with essential hypertension, but captopril-induced changes in blood pressure and renal hemodynamics and function were similar in both groups. In addition, 24-hours urinary albumin excretion was increased in OC users when compared with nonusers with similar arterial blood pressure. In 13 hypertensive women followed up for 6 months after OC withdrawal, a decrease in plasma renin activity, blood pressure, and glomerular filtration rate but no significant change in urinary albumin excretion and captopril-induced changes in blood pressure and renal hemodynamics were observed. These results indicate that the use of OC is associated with an increased albuminuria and no evidence of a prominent role for the renin-angiotensin system in the maintenance of high blood pressure and renal hemodynamics when compared with non-OC users with essential hypertension.

The existence of a direct relationship between body mass and arterial pressure is well recognized; however, the effect of obesity on known target organs of hypertension is not clearly understood. We undertook the present studies to assess the influence of obesity on renal function and urinary albumin excretion in 40 normotensive subjects and 80 nevertreated hypertensive patients matched for age, sex, arterial pressure level, and known duration of hypertension in whom an oral glucose tolerance test was within normal limits. Glomerular filtration rate and effective renal plasma flow (expressed as absolute values or values normalized for height) were increased in overweight compared with lean subjects whether normotensive or hypertensive. Glomerular filtration rate was positively correlated with protein intake (as assessed from urinary excretion of urea) and fasting serum insulin level. Urinary excretion of albumin but not IgG and beta 2 microglobulin was higher in hypertensive patients compared with normotensive subjects. The overweight condition clearly enhanced the influence of arterial pressure on albuminuria; in fact, a steeper regression line between albumin excretion rate and arterial pressure was found in overweight compared with lean subjects. These results indicate that the overweight condition is associated with renal hyperfiltration and hyperperfusion, irrespective of the presence of hypertension, and that obesity magnifies the effect of hypertension on albuminuria, thus raising the possibility of an increased susceptibility of obese hypertensive patients to the development of renal damage.

The influence of a 3-month antihypertensive treatment on cardiac structure and renal function was assessed in patients with uncomplicated essential hypertension randomly allocated to treatment by the nonselective beta-blocker tertatolol or the angiotensin-converting enzyme inhibitor enalapril. Both tertatolol and enalapril treatments were associated with a similar decrease in mean arterial pressure (-26 +/- 6 and -15 +/- 2 mm Hg, respectively, both p < 0.05 in comparison with baseline values) and left ventricular mass (echocardiography: -48 +/- 17 vs. -18 +/- 6 g) but no change in glomerular filtration rate (DTPA clearance). Renal vascular resistance decreased similarly in both groups. Urinary albumin excretion was not significantly modified in either group. These results indicate that a consistent reduction in arterial pressure by either treatment was associated with a proportional change in left ventricular geometry and no alteration in renal function.

The exaggerated natriuretic response to extracellular fluid volume expansion (VE) observed in essential hypertension (EH) is related directly to blood pressure (BP) and indirectly to plasma renin activity (PRA). In order to evaluate the precise role of different hormonal parameters, the response to acute VE (isotonic saline, 1,800 ml IV over 3 hours) was assessed in 14 patients with primary aldosteronism (PA, surgically proven adrenal adenoma) and 18 clinically matched EH. At the time of the maneuver, BP and sodium intake were similar in the two groups, but serum potassium (2.89 +/- 0.13 vs 3.69 +/- 0.09 mmol/l), PRA (0.9 +/- 0.2 vs 3.5 +/- 0.9 ng/ml/h) and plasma aldosterone concentration (PAC, 25.9 +/- 3.8 vs 12.6 +/- 1.6 ng/dl) were significantly different. During VE, sodium excretion (UNaV) increased more in PA than in EH (98.1 +/- 15.2 vs 63.5 +/- 7.9 mmol/3 h); moreover, the slope of the regression line relating UNAVVE to UNaVcontrol was significantly steeper in PA. By contrast, the change in BP and indices of VE (hematocrit and plasma protein concentration) as well as the decrease in PRA (-45 +/- 9 vs -43 +/- 5 p. 100) and the increase in ANP (+ 65 +/- 16 vs + 69 +/- 28 p. 100) were similar in the two groups. VE left PAC unchanged in PA, whilst it decreased PAC in EH. We conclude that the natriuretic response to volume expansion is more marked in primary aldosteronism than in essential hypertension, a difference which is not explained by variations in the renin-angiotensin system or atrial natriuretic peptide.