Renal sodium retention during upright posture in preascitic cirrhosis

Bernardl, Mauro; Marco, Claudio Di; Trevisani, Franco; Fornalè, Lorenzo; Andreoné, Pietro; Cursaro, Carmela; Baraldini, M.; Ligabue, A.; Tamè, Maria Rosa; Gasbarrini, Giovanni

doi:10.1016/0016-5085(93)90025-8

Cited by 89 publications

(77 citation statements)

References 17 publications

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“…Although BDL mice displayed significant hyperaldosteronemia, attested to by increased excretion of aldosterone and induction of sgk1 in CCD, experiments in corticosteroid-clamped animals definitely demonstrate that hyperaldosteronemia is not required for sodium retention, ascites formation and induction of Na ϩ ,K ϩ -ATPase in CCD in cholestatic mice. This is consistent with clinical observations of sodium retention in cirrhotic patients with normal renin activity and plasma aldosterone level 2,4,7,19,20,22 and experimental findings showing that adrenalectomy does not promote natriuresis in cirrhotic rats. 33 Altogether, these findings invalidate the underfill theories of sodium retention in liver cirrhosis and are compatible with a primary activation of sodium retention.…”

Section: Discussionsupporting

confidence: 92%

“…4 On the other hand, several reports indicated normal renin and aldosterone plasma levels in cirrhotic patients. 2,4,7,[19][20][21][22] Furthermore, saline loading decreased plasma renin and aldosterone in patients with cirrhosis without resolving sodium retention. 23 To reconcile these findings, it has been proposed that aldosterone sensitivity was increased in cirrhosis.…”

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confidence: 96%

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Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

et al. 2007

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Renal sodium retention in experimental liver cirrhosis originates from the distal nephron sensitive to aldosterone. The aims of this study were to (1) determine the exact site of sodium retention along the aldosterone-sensitive distal nephron, and (2) to evaluate the role of aldosterone and mineralocorticoid receptor activation in this process. Liver cirrhosis was induced by bile duct ligation in either adrenalintact or corticosteroid-clamped mice. Corticosteroid-clamp was achieved through adrenalectomy and corticosteroid supplementation with aldosterone and dexamethasone via osmotic minipumps. 24-hours renal sodium balance was evaluated in metabolic cages. Activity and expression of sodiumand potassium-dependent adenosine triphosphatase were determined in microdissected segments of nephron. Within 4-5 weeks, cirrhosis induced sodium retention in adrenal-intact mice and formation of ascites in 50% of mice. At that time, sodium-and potassium-dependent adenosine triphosphatase activity increased specifically in cortical collecting ducts. Hyperaldosteronemia was indicated by increases in urinary aldosterone excretion and in sgk1 (serum-and glucocorticoid-regulated kinase 1) mRNA expression in collecting ducts. Corticosteroid-clamp prevented induction of sgk1 but not cirrhosis-induced sodium retention, formation of ascites and stimulation of sodium-and potassiumdependent adenosine triphosphatase activity and expression (mRNA and protein) in collecting duct. These findings demonstrate that sodium retention in cirrhosis is independent of hyperaldosteronemia and of the activation of mineralocorticoid receptor. Conclusion: Bile duct ligation in mice induces cirrhosis which, within 4-5 weeks, leads to the induction of sodium-and potassium-dependent adenosine triphosphatase in cortical collecting ducts, to renal sodium retention and to the formation of ascites. Sodium retention, ascites formation and induction of sodium-and potassium-dependent adenosine triphosphatase are independent of the activation of mineralocorticoid receptors by either aldosterone or glucocorticoids. (HEPATOLOGY 2007;46:173-179.) See Editorial on Page 9 P atients with liver cirrhosis and portal hypertension develop renal sodium retention which promotes formation of ascites and peripheral edema. The "underfill theory" initially attributed sodium retention to secondary hyperaldosteronism accounted for by renal hypoperfusion brought about by intraabdominal fluid sequestration. 1 However, the underfill theory cannot explain the early phase of cirrhosis as sodium retention may precedes formation of ascites. 2-7 Thus, the "overflow theory" postulated that edema and ascites formation resulted from primary renal sodium retention promoting plasma volume expansion. 8 This theory is supported by the fact that abolishing portal hypertension in cirrhotic dogs by sideto-side portocaval shunt prevented ascites formation but not sodium retention. 5,6 Later, the "revised underfill theory" proposed that peripheral arterial vasodilatation leading to decreased effec...

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Section: Discussionsupporting

confidence: 92%

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confidence: 96%

Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

et al. 2007

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“…Indeed in human cirrhosis, myocardial hypertrophy could be an adaptive response to chronically expanded blood volume, since these patients have sodium and water retention, starting at the pre-ascitic stage of the disease [24,49]: notably at this early stage neuroendocrine overactivity is slight, becoming increasingly more severe as the cirrhotic process progresses [30]. Nevertheless, in previous studies sympathetic nerve outflow has been documented to be already in- creased even in the compensated stage of disease [50,51]: then the sympathetic nervous system could play a key role in the development of left ventricular hypertrophy in cirrhosis, as already clearly reported in hypertension [52].…”

Section: Discussionmentioning

confidence: 99%

Heart Function and Myocardial Tissue Characterization in Patients with HCV Related Cirrhosis: Diastolic Dysfunction and Cardiac Hypertrophy

Pozzi¹,

Pizzala²,

Ratti³

et al. 2007

TOGASJ

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Evidence of diastolic dysfunction in cirrhosis contributed to the definition of cirrhotic cardiomyopathy. In 109 patients with chronic HCV infection with or without cirrhosis E/A ratio, a Doppler marker of diastolic dysfunction, was decreased in cirrhotics (0.89 ± 0.03 vs controls 1.21 ± 0.07, p < 0.01) and to a lesser extent in patients with advanced liver fibrosis (1.17 ± 0.07, p < 0.01). Left ventricular parietal wall thickness was increased. The nature of this abnormality in human cirrhosis has not been clarified, animal studies reporting cardiac hypertrophy. To this aim we employed the echocardiographic integrated backscatter (IBS) technique to obtain an indirect estimate of tissue density (decreased when a higher percentage of muscle fibres is present and increased when fibrosis prevails) to provide myocardial tissue characterization in a subset of patients with compensated HCV cirrhosis. The average IBS signal was reduced in cirrhotics at the level of the posterior wall (21.72 ± 1.46 dB versus 30.85 ± 1.40 dB in controls, p < 0.01). Our results confirm diastolic dysfunction in postviral cirrhosis pointing to cardiac hypertrophy as the anatomopathological background in the compensated stage of disease.

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“…36 Whereas all authors agree that increased renal sodium retention occurs in cirrhosis, the opinions differ with respect to temporal relationship, mechanism, and quantitative relevance of aldosterone. 1,[37][38][39][40][41][42][43] Aldosterone receptors are transcription factors that can be activated not only by the mineralocorticosteroid aldosterone, but also by the endogenous glucocorticosteroids, cortisol and corticosterone. 6 Under normal conditions, however, only aldosterone, but not cortisol or corticosterone, has access to the MR, because a gate-keeper enzyme, the 11␤-HSD2, converts cortisol and corticosterone into glucocorticosteroids devoid of affinity for the MR, namely cortisone and dehydrocorticosterone, respectively.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of 11?-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

et al. 1999

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Renal sodium retention and potassium loss occur early, in many instances in the preascitic state of cirrhosis, an observation that cannot be fully explained by increased aldosterone concentrations. We therefore hypothesize that 11␤-hydroxysteroid dehydrogenase 2 (11␤-HSD2), which protects mineralocorticoid receptors (MR) from glucocorticosteroids, is down-regulated in cirrhosis. Cirrhosis was induced by bile duct ligation in rats. The urinary ratio of (tetrahydrocorticosterone ؉ 5␣-tetrahydrocorticosterone)/ 11-dehydro-tetrahydrocorticosterone [(THB؉5␣-THB)/ THA] was measured by gas chromatography. Cortical collecting tubules (CCT) were isolated by microdissection and used for measurements of the activity of 11␤-HSD2 by assessing the conversion of corticosterone to dehydrocorticosterone. The mRNA content of 11␤-HSD2 was determined by reverse-transcription polymerase chain reaction (RT-PCR) in CCTs. The urinary ratio of (THB؉5␣-THB)/ THA increased concomitantly with the urinary excretion of bile acids following bile duct ligation. Chenodeoxycholic acid (CDCA) dose-dependently inhibited 11␤-HSD2 in CCT with a Ki of 19.9 mol/L. Four weeks after bile duct ligation, 11␤-HSD2 activity was decreased in CCT, an observation preceded by a reduced mRNA content at weeks 2 and 3. In cirrhosis, the MR-protecting effect by 11␤-HSD2 is diminished, and therefore, endogenous glucocorticoids can induce MR-mediated sodium retention and potassium loss. (HEPATOLOGY 1999;30:623-629.)Renal sodium retention and potassium loss are observed in patients suffering from cirrhosis. Traditionally, this abnormality was attributed to secondary hyperaldosteronism as a consequence of renal hypoperfusion related to intraabdominal fluid sequestration.

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Renal sodium retention during upright posture in preascitic cirrhosis

Cited by 89 publications

References 17 publications

Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

Heart Function and Myocardial Tissue Characterization in Patients with HCV Related Cirrhosis: Diastolic Dysfunction and Cardiac Hypertrophy

Inhibition of 11?-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

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