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Editor,—We read with interest the commentary by Clària and Rodés (OpenUrlAbstract/FREE Full Text) on our paper published inGut which re-examined the mechanisms of renal sodium retention in patients with preascitic cirrhosis.1 In summary, in our patients we observed indirect evidence of expanded central vascular fluid volume compared with healthy controls and thought this physiopathological alteration was due to slightly reduced values of glomerular filtration rate (measured as creatinine clearance) and, mainly, to increased distal tubular retention of sodium when expressed as a fraction of the filtered sodium load that is reabsorbed by the distal nephron (26.9 (6.7)% v 12.5 (3.4)%, respectively; p<0.05).1
Clària and Rodés advanced two criticisms and affirmed that our results, obtained by means of the lithium clearance and fractional excretion technique, may be influenced by two fundamental flaws. 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 been proved due to possible lithium reabsorption in the distal nephron.2 Secondly, in Clària and Rodés's opinion, our observation of more avid fractional sodium reabsorption by the distal nephron in compensated cirrhosis merely reflects diminished delivery of fluid and sodium to the distal segments (due to reduced glomerular filtration) rather than increased distal tubular sodium reabsorption.
With reference to the first methodological remark, to our knowledge the value of fractional sodium excretion (FENa) below which lithium reabsorption beyond the proximal tubule occurs is 0.02% and not 0.4%.3 ,4 Obviously, our non-azotaemic preascitic cirrhotics displayed values of FENa well above this threshold (0.76 (0.39)%).1
Concerning the second remark, although our patients displayed slightly lower values of creatinine clearance (CCr) with respect to controls, the calculated deliveries of fluid and sodium to the distal nephron were not lower but somewhat higher, even if not significantly, than in healthy subjects (30.7 (9.3) v 27.5 (6.7) ml/min and 4.25 (1.30) v 3.9 (1.0) mEq/min, respectively; all p>0.05).1 In effect, not surprisingly, we observed no correlation between values of CCr and distal delivery of fluid or sodium.1 Furthermore, because of the inverse correlation in the cirrhotic group between levels of plasma active renin and lithium clearance, we reaffirm a compensatory role for the proximal renal tubule as it seems capable of delivering more fluid and sodium to the loop of Henle during a progressive increase in circulating fluid volume, at least at this stage of disease.1
In conclusion, we agree with Clària and Rodés that some uncertainty may be introduced in studies assessing renal function in cirrhosis by measurement of glomerular filtration rate using creatinine clearance. However, we consider that our results on inappropriate avidity of sodium reabsorption by the distal nephron are relevant in explaining the already demonstrated increase in central fluid volume in patients with preascitic cirrhosis.5
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Reply
Editor,—In their letter, Sansoè and Ferrari make some excellent points on our accompanying commentary (OpenUrlFREE Full Text) to their paper published in (OpenUrlAbstract/FREE Full Text). In that paper, Sansoèet al investigated the status of central blood volume and examined the distribution of sodium reabsorption along the segments of the renal tubule in a group of 12 preascitic cirrhotic patients. Whereas the results on central fluid volume were quite conclusive, the findings on renal function merit some discussion (OpenUrlFREE Full Text). As precisely pointed out by Sansoè and Ferrari in their letter, the contention was mainly methodological and was related to the use of lithium and creatinine clearances for determination of distal sodium reabsorption and glomerular filtration rate, respectively.
Lithium clearance is a useful marker of proximal tubule sodium handling because in theory this ion is reabsorbed in proportion to sodium and water along the entire proximal tubule.1-1 However, the validity of this method is not widely recognised. In this regard, there is compelling evidence that lithium is actively reabsorbed along the distal tubule in conditions characterised by low fractional sodium excretion.1-2 In healthy subjects, the estimated limit of fractional sodium excretion below which this problem arises has been established as 0.02%.1-3 Conversely, comprehensive studies of micropuncture have revealed that this value may vary from 0.4% to 0.65% in sodium depleted states.1-4 1-5 Finally, a value of fractional sodium excretion of 1% has been proposed as a safer limit by Koomans and colleagues.1-6 Thus, inasmuch as the value of fractional sodium excretion below which lithium clearance is disqualified as an index of proximal sodium delivery remains unresolved in cirrhosis, data derived from this method in cirrhotic patients should be interpreted with caution.
We should also point out that preascitic cirrhotic patients included in Sansoè et al's study (OpenUrlAbstract/FREE Full Text) had significantly lower values than controls for glomerular filtration rate, as determined by creatinine clearance. These findings are not consistent with those previously reported in compensated cirrhotics using more sensitive clearance techniques such as inulin clearance.1-7
In summary, it is gratifying to see that Sansoè and Ferrari agree that a certain amount of uncertainty may be introduced in studies dealing with renal function by using creatinine and lithium clearances. We believe that their paper will undoubtedly foster new studies investigating the central fluid volume status and renal tubular avidity for sodium in preascitic cirrhotic patients.