Renal sodium retention in pre-ascitic cirrhosis: The more we know about the puzzle, the more it becomes intricate

Abstract

Semeiotica Medica, Dipartimento di Medicina Clinica, Alma Mater Studiorum – Universita di Bologna, ItalySee Article, pages 856–862Ascites develops in 5–10% of patients with compensated cirrhosisper year and carries an ominous prognosis [1]. The appropriatemanagement and possible prevention of this complication obvi-ously depends on an in-depth knowledge of ascites pathophysiol-ogy, which remains somewhat elusive despite many studies thathave addressed the topic over decades. There is no doubt thatpost-sinusoidal portal hypertension is the main ‘‘local” pathoge-netic factor, and renal sodium retention is the main ‘‘systemic”event leading to a positive fluid balance and, ultimately, ascitesformation. However, uncertainties surround both the efferent(that is the factors/systems promoting renal sodium retention)and afferent (that is the factors that activate efferent mecha-nisms) factors associated with renal sodium handling abnormal-ities [2]. Sodium balance has been demonstrated to becomepositive before ascites formation both in animal models of cirrho-sis and humans [3–6]. Study of the early mechanisms leading toascites would help unveil its pathophysiology in a stage of thedisease where further complications involving systemic hemody-namics and renal function may act as confounding factors. In thisissue of the Journal of Hepatology, Sansoe and co-workers pres-ent a fine study on an efferent mechanism potentially leadingto renal sodium retention in pre-ascitic cirrhosis [7].It has been convincingly demonstrated, both in animal modelsof cirrhosis and patients, that pre-ascitic renal sodium retentionoccurs while the glomerular filtration rate is well-preserved, indi-cating that sodium handling abnormalities reside at the tubularlevel [3–6]. Micropuncture studies performed in dogs withdimethylnitrosamine-induced cirrhosis showed that sodiumresorption by the proximal convoluted tubule and hence sodiumdelivery to the more distal nephron segments are not impaired[3]. This demonstrates that sodium retention occurs beyond theproximal convoluted tubule, and implies that both Henle’s loopand the collecting duct could be involved.In line with the hypothesis that the collecting duct, the aldo-sterone-sensitive portion of the nephron, is the main site ofsodium retention, is the demonstration that a progressiveincrease in positive sodium balance paralleled an increase inurinary aldosterone excretion in rats with pre-ascitic CCl