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Loss of Tubuloglomerular Feedback in Decompensated Liver Cirrhosis: Physiopathological Implications

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Abstract

In healthy subjects, arterial pressure reduction or renal ischemia produces renal artery dilatation through autoregulation and tubuloglomerular feedback (TuGF). Patients with decompensated cirrhosis have reduced kidney perfusion pressure but show renal vasoconstriction instead of autoregulation-mediated vasodilation. This study investigates the consequences of kidney autoregulation loss on renal perfusion, glomerular filtration rate, and tubular handling of electrolytes in both compensated and ascitic nonazotemic cirrhotic patients. Forty-two consecutive patients with diuretic-free liver cirrhosis (32 with preascitic and 10 with ascitic disease) and 10 controls were submitted to the following determinations: (a) basal plasma renin activity and aldosterone levels; (b) endogenous dopaminergic activity measured as incremental aldosterone responses during metoclopramide administration; and (c) renal clearances of sodium, potassium, inulin, para-aminohippurate and lithium. Compared with the other groups, ascitic patients showed lower renal plasma flow (P < 0.01) and lithium clearance (P < 0.05), a higher filtration fraction (P < 0.01), and secondary aldosteronism. Controls and preascitic patients displayed tubuloglomerular feedback (the mechanism increasing the glomerular filtration rate when a reduced sodium load reaches the distal tubule), as demonstrated by negative correlations between fractional excretion of lithium (an expression of fractional delivery of sodium to the distal nephron) and glomerular filtration rate (respectively, r = −0.73, P < 0.03, and r = −0.48, P < 0.01). Conversely, patients with ascites showed a positive correlation between lithium fractional excretion and glomerular filtration rate (r = 0.64, P < 0.05). Reduction in renal perfusion, increased filtration fraction, and TuGF derangement, as found in decompensated patients, are indicative of prevalent postglomerular arteriolar vasoconstriction, with ensuing stimulation of proximal tubular sodium reabsorption.

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Authors and Affiliations

  1. Gastroenterology Unit, Gradenigo Hospital, Torino, Italy

    Giovanni Sansoè MD & Mario Rizzetto MD

  2. Department of Gastroenterology, Molinette Hospital, University of Torino, Torino, Italy

    Stefano Silvano MD, Antonina Smedile MD, Giovanni Touscoz MD & Floriano Rosina MD

  3. Institute of General Pathology, Molinette Hospital, Torino, Italy

    Giulio Mengozzi MD

  4. Divisione di Gastroenterologia, Ospedale Gradenigo, C.so Regina Margherita 10, 10153, Torino, Italy

    Giovanni Sansoè MD

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  1. Giovanni Sansoè MD
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  2. Stefano Silvano MD
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Sansoè, G., Silvano, S., Mengozzi, G. et al. Loss of Tubuloglomerular Feedback in Decompensated Liver Cirrhosis: Physiopathological Implications. Dig Dis Sci 50, 955–963 (2005). https://doi.org/10.1007/s10620-005-2671-0

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  • DOI: https://doi.org/10.1007/s10620-005-2671-0

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