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Renal sodium handling in pre-ascitic cirrhosis
  1. J CLÀRIA,
  2. J RODÉS
  1. Liver Unit
  2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
  3. Hospital Clínic
  4. Universitat de Barcelona
  5. Spain

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See article on page 750

Sodium retention leading to the accumulation of fluid within the abdominal cavity in the form of ascites is the most common renal functional abnormality in advanced decompensated cirrhosis.1 The predominant mechanism underlying sodium retention in these patients is increased renal tubular sodium reabsorption secondary to exacerbated activity of the endogenous vasoactive systems and sodium retaining mechanisms. In fact, in cirrhosis and ascites, sodium retention takes place in the setting of a normal or moderately reduced glomerular filtration rate and increased activity of the renin-angiotensin-aldosterone system, one of the most powerful vasoconstrictor systems involved in body fluid homoeostasis.1 2

Whereas in decompensated cirrhosis the mechanism that initiates sodium retention and ascites formation is quite well established, in pre-ascitic cirrhosis it still remains a subject of interest and debate. Patients with compensated cirrhosis (patients without ascites on a normal sodium diet and without diuretics) usually do not exhibit sodium retention.1 Moreover, the activity of the renin-angiotensin-aldosterone system, estimated by plasma renin activity and circulating concentrations of aldosterone, is consistently found to be either normal or decreased in pre-ascitic cirrhotic patients.1 2 These patients, however, have subtle abnormalities in renal sodium handling leading to an expanded circulatory blood volume but without causing ascites or oedema. Indeed, the existence of altered renal sodium metabolism in pre-ascitic cirrhotic patients can be uncovered readily by administering a sodium overload or following mineralocorticoid treatment.1Therefore, and although not clinically evident, pre-ascitic cirrhotic patients have a positive sodium balance which presumably is a homoeostatic mechanism to compensate for the reduced effective arterial blood volume as a result of arteriolar vasodilatation.

In this issue (see page 750), Sansoè and coworkers have re-examined circulatory volume status in pre-ascitic cirrhotic patients. To this end, plasma concentrations of active renin and aldosterone and dopaminergic activity were measured in 12 patients with Child-Pugh class A cirrhosis and nine controls on a normal sodium diet. Dopaminergic activity was assessed by the incremental aldosterone responses to the intravenous administration of metoclopramide, a dopamine DA2 receptor antagonist, and relies on the tonic inhibitory effect of endogenous dopamine on adrenal mineralocorticoid secretion. Compared with controls, patients with pre-ascitic cirrhosis had increased dopaminergic activity, which inversely correlated with active renin plasma concentrations. The authors perceived these findings as evidence of an expanded central plasma volume and consequently proposed the assessment of dopaminergic activity as a novel, reliable and useful marker of fluid volume status in cirrhosis.

More importantly, Sansoè et al also investigated the distribution of sodium reabsorption along the segments of the renal tubule in pre-ascitic cirrhotics by means of lithium clearance. The lithium clearance method is a very useful index of fluid delivery to the distal tubule and is based on the assumption that this ion is reabsorbed in the proximal tubule in parallel with sodium and water. This method has been widely used to evaluate intrarenal sodium handling in humans and animals3-5 and has been useful in elucidating that the proximal portion of the nephron is the main site of increased sodium reabsorption in cirrhosis with ascites.6 However, two main criticisms have been raised against the use of this technique in cirrhosis. Firstly, the reliability of lithium clearance as a marker of distal fluid delivery in clinical conditions characterised by low fractional sodium excretion (below 0.40%) has not yet been proved.7 Secondly, it is not clear whether lithium transport also occurs beyond the proximal tubule (i.e., Henle’s loop) in cirrhosis.8 Using the lithium clearance method, Sansoè et alreport the existence of increased distal fractional sodium reabsorption in pre-ascitic cirrhotic patients. This conclusion arises from the calculation of distal fractional sodium reabsorption as the result of dividing values of absolute distal sodium reabsorption by those for filtered sodium load. However, and contrary to what was expected and observed in previous investigations,1 2 the pre-ascitic cirrhotic patients had significantly lower values for the glomerular filtration rate and filtered sodium load. Therefore, in these patients the calculated increase in distal fractional sodium reabsorption reflects diminished delivery of fluid to the distal segment rather than increased distal tubular sodium reabsorption. In fact, when the authors calculated distal fractional sodium reabsorption as a function of absolute distal sodium reabsorption divided by absolute distal sodium delivery, no differences were obtained for tubular sodium handling between cirrhotic and control groups. Whether similar values in glomerular filtration rate would be obtained by estimating this parameter with more sensitive clearance techniques, such as inulin clearance, is not known. Taken together and although further studies are needed to characterise fully intrarenal sodium handling in pre-ascitic cirrhotic patients, Sansoè et al’s paper does bring to our attention the notion that central fluid volume derangements and renal tubular sodium avidity are unequivocally two critical events in compensated cirrhosis.

See article on page 750


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