Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension.

Dworkin, Lance D.; Hostetter, Thomas H.; Rennke, Helmut G.; Brenner, Barry M.

doi:10.1172/jci111349

Cited by 256 publications

(112 citation statements)

References 40 publications

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“…In a 9-yr follow-up study, we showed that primary aldosteronism is characterized by partially reversible renal dysfunction (20), and demonstration that albuminuria is a marker of a hemodynamic rather than a structural renal defect has been reported also by Ribstein et al (19) in a short-term, postadrenalectomy evaluation of patients with adrenal adenoma. In agreement with the findings of studies that were conducted in more experimental settings (37)(38)(39), longitudinal studies consistently demonstrate that the hallmark of renal dysfunction in primary aldosteronism is reversible glomerular hyperfiltration that contributes to increase urinary albumin losses.…”

Section: Discussionsupporting

confidence: 84%

Relationships of Plasma Renin Levels with Renal Function in Patients with Primary Aldosteronism

Catena¹,

Colussi²,

Nadalini³

et al. 2007

Clinical Journal of the American Society of Nephrology

102

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Background: The renal damage that is present in primary aldosteronism might reflect functional and potentially reversible abnormalities that are initiated by glomerular hyperfiltration. The aim of this study was to investigate the relationships of plasma renin and aldosterone concentrations with renal outcomes after treatment of primary aldosteronism.Design, setting, participants, and measurements: Fifty-six consecutive patients who had primary aldosteronism and were recruited in a university center were studied. Patients were prospectively followed after either surgical or medical treatment for a mean of 6.2 yr, during which they received antihypertensive drugs to reach a target BP of <140/90 mmHg.Results: At baseline, patients with primary aldosteronism had higher creatinine clearance and albuminuria than 323 patients with essential hypertension and 113 normotensive individuals. In patients with primary aldosteronism, plasma active renin levels that were higher than the lower limit of detection (2.5 pg/ml) were associated with higher BP, plasma potassium, and albuminuria and lower creatinine clearance. Plasma aldosterone concentrations that were higher than the median value (225 pg/ml) were associated with lower plasma potassium and higher creatinine clearance. Creatinine clearance was correlated directly with plasma aldosterone and inversely with renin. During follow-up, patients with higher baseline plasma renin required use of more antihypertensive drugs to obtain BP control and had a smaller early decline in albuminuria than did patients with suppressed renin.Conclusions: Escape of renin from suppression by excess aldosterone is associated with evidence of more severe renal damage in patients with primary aldosteronism and predicts less favorable outcomes after treatment.

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Section: Discussionsupporting

confidence: 84%

Relationships of Plasma Renin Levels with Renal Function in Patients with Primary Aldosteronism

Catena¹,

Colussi²,

Nadalini³

et al. 2007

Clinical Journal of the American Society of Nephrology

102

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“…A more accelerated course of renal disease was also observed in other experimental models of salt-sensitive hypertension, such as in the deoxycorticosterone acetate-salt hypertensive rat, 40 the uninephrectomized SHR, 41 the Holtzman postsalt model of hypertension, 42 and the Milan strain of SHR. 43 All of these salt-sensitive models of hypertension manifest a decrease in afferent arteriolar resistance and a rise in glomerular pressure in response to an increase in blood pressure.…”

mentioning

confidence: 52%

Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors.

Bigazzi¹,

Bianchi²,

Baldari³

et al. 1994

Hypertension

237

133

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We previously showed that a high salt diet increases glomerular capillary pressure in salt-sensitive hypertensive patients and suggested that this may underlie the greater propensity of these patients to develop renal failure. Because microalbuminuria is considered an initial sign of renal damage, we have tested whether salt-sensitive patients display greater urinary albumin excretion than salt-resistant hypertensive patients. Twenty-two patients were placed on a low sodium intake (20 mEq/d) for 7 days followed by a high sodium diet (250 mEq/d) for 7 more days. Twelve patients were classified as salt sensitive and 10 as salt resistant. Urinary albumin excretion was greater in salt-sensitive than saltresistant patients (54±11 versus 22±5 mg/24 h, P<.01). During the low sodium diet, glomerular filtration rate, renal plasma flow, and filtration fraction were similar between the two groups. During the high sodium intake, glomerular filtration, renal plasma flow, filtration fraction, and calculated intraglomerular pressure did not change in salt-resistant patients; in salt-sensitive patients, however, renal plasma flow decreased, and filtration fraction and intraglomerular pressure increased, whereas glomerular filtration rate did not change. Urinary albumin excretion was significantly correlated with glomerular capillary pressure. Salt-sensitive patients displayed higher serum levels of low-density lipoprotein cholesterol and lipoprotein(a) and lower levels of high-density lipoprotein cholesterol than salt-resistant patients. These studies have shown greater urinary albumin excretion and serum concentrations of atherogenic lipoproteins in salt-sensitive than in salt-resistant hypertensive patients, suggesting that salt sensitivity may be a marker for greater risk of renal and cardiovascular complications. (Hypertension. 1994;23:195-199.)

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“…It was reported that in vitro addition of aldosterone may exert a direct and rapid vasoconstrictive effect on the efferent renal arteriole (20) or that aldosterone abolished the vasoconstriction induced by potassium chloride at the afferent (preglomerular) level (21). In uninephrectomized rats with desoxycorticosterone-salt hypertension, glomerular injury resulted from elevation in glomerular capillary flow and pressure, and discontinuation of desoxycorticosterone administration was associated with a partial recovery of glomerular injury and a consistent decrease in albuminuria (22). Whether the fall in GFR observed after adrenalectomy may result from the removal of the renal escape to aldosterone through a reduction in nitric oxide (17,23) or, on the contrary, less aldosterone suppression of nitric oxide bioavailability (24) needs further studies with direct assessment of the potential intermediate mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Relative Glomerular Hyperfiltration in Primary Aldosteronism

Ribstein¹,

Cailar²,

Fesler³

et al. 2005

Journal of the American Society of Nephrology

181

172

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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 131 I-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 ␤2 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 ␤2 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 m 2 , 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.J P rimary aldosteronism (PA) is a possibly common form of endocrine hypertension in which aldosterone production is inappropriate and at least partially autonomous with regard to physiologic control by angiotensin. In recent years, the widespread use of the plasma aldosterone/ renin ratio as a screening test for PA has led to a marked increase in the proportion of hypertensive patients identified as such (1). Whether the diagnostic workup of aldosterone-producing adenomas is cost-effective regarding the potential for curability or effective protection of target organs by specific treatment remains controversial (2). Several experimental and, to a lesser extent, clinical studies suggest that long-term exposure to increased aldosterone levels may result in renal as well as cardiac and vascular toxicity that is in part independent of the BP level (3,4). Target organ damage, as assessed by the measurement of left ventricular mass or urinary excretion of albumin, may be inappropriately high with respect to the BP level in patients with PA (5,6). However, the relationship between albuminuria and renal function parameters is not clear. Specifically, it is not known whether PA-associated albuminuria may relate to a state of hyperfiltration suggested in a study in which GFR was assessed by the measurement of creatinine clearance (7). For investigating the effect of aldosterone excess...

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Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension.

Cited by 256 publications

References 40 publications

Relationships of Plasma Renin Levels with Renal Function in Patients with Primary Aldosteronism

Relationships of Plasma Renin Levels with Renal Function in Patients with Primary Aldosteronism

Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors.

Relative Glomerular Hyperfiltration in Primary Aldosteronism

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