Characterization of the renin-aldosterone system in decompensated cirrhosis.

Abstract

SUMMARY' Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI) produces a prompt and profound suppression of plasma renin (PRA) and plasma aldosterone (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was used to assess the responsiveness of both PRA and PA in cirrhosis. Sixteen cirrhotic patients were studied twice while in balance on a 10 mEq sodium, 100 mEq potassium diet, under control conditions and during NI. The conditions of seated posture and time of day were identical. Plasma for PRA and PA was obtained at 30-minute intervals for 6 hours. NI produced profound suppression of PRA as early as 60 minutes with maximal suppression (70%) by 150 minutes (P < 0.005). Recovery from NI was associated with a prompt return to prestudy levels. PA was suppressed within 60 minutes with a maximal suppression of 59% by 240 minutes (P < 0.005) and a prompt return to prestudy levels during recovery. The suppression of PA paralleled that of PRA throughout the immersion period (P < 0.005). Although 15 of the 16 subjects manifested a significant suppression of PA, eight subjects manifested either a blunted or absent natriuretic response during NI. These data demonstrate that the elevated PRA and PA levels of cirrhosis are suppressed promptly and markedly in response to a standardized volume stimulus. The parallelism of changes in PRA and PA supports the importance of the renin-angiotensin axis in the control of volume-regulated changes in PA in cirrhotic man. Finally, our demonstration of the dissociation between the marked suppression of circulating PA and the absence of a natriuresis in eight of these subjects suggests strongly that aldosterone plays only a permissive role in relation to the impaired sodium excretion of cirrhosis. DESPITE documentation of excessive levels of plasma renin activity (PRA) and plasma aldosterone concentration (PA) in patients with decompensated alcoholic cirrhosis, the responsible mechanism or mechanisms remain controversial. 1 " 8 Furthermore, the responsiveness of PRA and PA to alterations of extracellular fluid volume and postural stimuli are uncertain and there is a recent report suggesting that PRA and PA are unaffected by extracellular fluid volume expansion in many cirrhotic patients. 4 The assessment of the responsiveness of PRA and PA to volume alteration has been confounded by the distinct hazard of infusing exogenous volume expanders in patients who already are markedly volume-expanded. Furthermore, sequential sampling of blood for kinetic assessment of PA produces a degree of volume contraction which, in and of itself, may perturb the experimental results. Since recent studies from our laboratory have demonstrated that the central hypervolemia induced by immersion produces a prompt and profound suppression of the renin-aldosterone system without concomitant alteration of plasma composition, 9 " 12 we undertook to char