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Renal tubular events following passage from the supine to the standing position in patients with compensated liver cirrhosis: loss of tubuloglomerular feedback
  1. G Sansoé1,
  2. A M Biava2,
  3. S Silvano2,
  4. A Ferrari3,
  5. F Rosina1,
  6. A Smedile2,
  7. A Touscoz2,
  8. L Bonardi1,
  9. M Rizzetto2
  1. 1Gastroenterology Unit, Gradenigo Hospital, Torino, Italy
  2. 2Department of Gastroenterology, Molinette Hospital, Torino, Italy
  3. 3Chair of Gastroenterology, Department of Internal Medicine, University of Modena, Modena, Italy
  1. Correspondence to:
    Dr G Sansoé, Divisione di Gastroenterologia, Ospedale Gradenigo, Corso Regina Margherita 10, 10153 Torino, Italy;
    giovannisan{at}iol.it

Abstract

Background and aims: Patients with preascitic liver cirrhosis display significant renal sodium retention in the upright posture and an exaggerated natriuresis during recumbency. To date, intrarenal sodium handling in these patients has not been studied using lithium clearance and fractional excretion techniques during recumbency and orthostatism.

Methods: Ten patients with preascitic (Child-Pugh A) liver cirrhosis and 10 healthy subjects underwent the following measurements during recumbency and then after four hours of standing: (a) active renin and aldosterone plasma levels; and (b) renal clearance of creatinine, sodium, potassium, and lithium (an index of fluid delivery to the loop of Henle).

Results: Unlike the control group, in the upright posture patients had significantly lower values of lithium clearance and fractional excretion compared with recumbency (21.6 (8.6) v 30.5 (10.2) ml/min (p<0.03) and 12.8 (4.4)% v 20.8 (4.9)% (p<0.01), respectively). Our patients showed maintenance of the glomerular-tubular balance—that is, the correlation between creatinine clearance and proximal tubular reabsorption of fluid—during both recumbency and in the upright posture (r=0.96, p<0.001; r=0.97, p<0.001, respectively). In contrast, patients displayed tubuloglomerular feedback only in the supine position. This was demonstrated by the observation of a negative correlation between lithium fractional excretion (a measure of the fractional delivery of sodium to the distal nephron) and filtered sodium load only in recumbency (r=−0.73; p< 0.03) and not during standing (r=0.22; p> 0.05).

Conclusions: This study suggests that both the reduction in fluid and sodium delivery to the distal nephron and loss of tubuloglomerular feedback (the mechanism increasing glomerular filtration rate when the distal tubule is reached by a reduced sodium load) contribute towards the tendency to sodium retention in compensated cirrhosis during prolonged upright posture.

  • cirrhosis
  • sodium retention
  • lithium clearance
  • upright posture
  • ascites
  • AR, active renin
  • CCr, creatinine clearance
  • CK, potassium clearance
  • CLi, lithium clearance
  • CNa, sodium clearance
  • DD, distal fluid delivery
  • DDNa, distal sodium delivery
  • DRNa, distal sodium reabsorption
  • DFRNa, distal fractional sodium reabsorption
  • FEK, fractional potassium excretion, FELi, fractional lithium excretion
  • FENa, fractional sodium excretion
  • FlNa, filtered sodium load
  • GFR, glomerular filtration rate
  • P-Cr, plasma creatinine concentration
  • P-K, plasma potassium concentration
  • P-Li, plasma lithium concentration
  • P-Na, plasma sodium concentration
  • PFR, proximal tubular reabsorption of fluid
  • PTRNa, proximal tubular reabsorption of sodium
  • U-Cr, urinary creatinine concentration
  • U-K, urinary potassium concentration
  • U-Li, urinary lithium concentration
  • U-Na, urinary sodium concentration
  • UNaV, urinary sodium excretion

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Footnotes

  • This study was presented in part at the 1999 Annual Meeting of the American Association for the Study of Liver Disease (AASLD), Dallas, Texas, USA, November 1999; at the 1999 Annual United European Gastroenterology Week (UEGW), Rome, Italy, November 1999; at the 2000 Annual Meeting of the Italian Association for the Study of the Liver (AISF), Rome, Italy, February 2000; and at the 35th Annual Meeting of the European Association for the Study of the Liver (EASL), Rotterdam, the Netherlands, May 2000.

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