Internal dysregulation of the renin system in patients with stable liver cirrhosis

Abstract

Sodium retention in cirrhosis is associated with changes in the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and the glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute reactions of RAAS and SNS to volume expansion are qualitatively intact, but occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and renal responses to central blood volume changes were studied in cirrhotic patients and healthy controls. In patients, baseline plasma renin concentration (PRC) was elevated 5-fold compared to controls (p < .001); it increased during standing (+144%, p < .001) and remained elevated during subsequent sitting (+118%, p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated significantly (14 ± 2 vs. 9 ± 2 pg/mL) in contrast to plasma aldosterone (pAldo, +160%, p < .001). During orthostatic RAAS activation, the rise in pAngII per unit increase in PRC was 0.04 pg AngII/mIU and 0.48 pg AngII/mIU in patients and controls, respectively (p < .001); similarly, the change in pAldo per unit change in pANGII was 3.6 in patients and 14.5 pg/pg in controls (p < .001). Plasma noradrenaline was elevated in the patients, but the dynamic changes were virtually identical to those of controls. During standing, abrupt decreases in renal blood flow (−63%, p < .001) and GFR (−42% p < .04) occurred only in patients. In conclusion, in stable cirrhosis, static and dynamic dysregulation exists within the RAAS; in the supine position pAngII levels are inappropriately low, and the AngII-mediated regulation of aldosterone secretion is severely impeded. In cirrhotic patients, profound reductions in renal blood flow and GFR occur during standing.

Keywords:

• Adrenal function
• liver cirrhosis
• renal failure
• renin-angiotensin system
• sympathetic nervous system

Acknowledgements

The authors appreciate the excellent technical assistance of Mette Svendsen and Bodil Christensen. The Lundbeck Foundation and the Fund of Odense University Hospital provided financial support.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by Lundbeckfonden and Region of Southern Denmark.