Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and ¹³¹I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and β2 microglobulin were higher in PA than EH (88 ± 26 versus 39 ± 12 and 0.91 ± 0.23 versus 0.26 ± 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 ± 3/13 ± 2 mmHg), urinary excretion of albumin and β2 microglobulin (by 48 ± 19 and 0.53 ± 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 ± 3 and 54 ± 15 ml/min per 1.73 m², respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.

A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. Prospective, controlled, randomized animal study. University research laboratory. Fifteen anesthetized dogs. Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.

Albuminuria is a well-known predictor of poor renal outcomes in patients with type 2 diabetes and in essential hypertension (1–4). Albuminuria has also been shown more recently to be a predictor of cardiovascular outcomes in these populations (5–8). There is emerging data that reduction of albuminuria leads to reduced risk of adverse renal and cardiovascular events (9–12). It has become increasingly clear that albuminuria should not only be measured in all patients with type 2 diabetes and hypertension, but also steps should be taken to suppress albuminuria to prevent future renal and cardiovascular adverse events. This review discusses the measurement of albuminuria and summarizes the current literature on the association between albuminuria and adverse cardiovascular and renal outcomes in type 2 diabetes and hypertension. It also summarizes the evidence that reduction of albuminuria leads to improvement in the risk profiles of these patients. Microalbuminuria is defined as levels of albumin ranging from 30 to 300 mg in a 24-h urine collection (13). Overt albuminuria, macroalbuminuria, or proteinuria is defined as a urinary albumin excretion of ≥300 mg/24 h. Urinary albuminuria comprises 20–70% or urinary total protein excretion. Measuring urinary albumin excretion by dipstick without simultaneously measuring creatinine is subject to false-negative and false-positive results due to variations in urine concentration caused by hydration level (13). Although urinary dipsticks are acceptable for quick screening, other more precise measurements should be done to quantify urinary albumin excretion rates (AERs). Albuminuria can be measured in several ways (Table 1): 1 ) measurement of albumin-to-creatinine ratio (ACR) in a random or first morning spot collection, 2 ) 24-h urine collection with measurement of creatinine to verify adequacy of the collection, and 3 ) timed (4-h or overnight) urine collections (13). Although the 24-h urine collection would overcome issues of diurnal variation …

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 ( ^99m Tc)-DTPA and ¹³¹ I-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.

Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. Prospective, controlled, randomized animal study. University research laboratory. Fourteen anesthetized piglets. Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 μg/kg was administered in 10 mins followed by 0.2 μg/kg/min or same volumes of isotonic saline. Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 ± 0.17 to 5.58 ± 0.37 mm Hg/mL, decreased Ees from 1.75 ± 0.12 to 1.29 ± 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 ± 0.20 to 0.24 ± 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.