Florence S-H Wong, MD, MBBS, FRCPC

Sodium and Water Retention in Cirrhosis

My main interest is in the pathophysiological changes that lead to sodium and water retention and hence ascites development in cirrhosis. The areas that I have investigated include abnormalities in hormonal profile, abnormal renal sodium handling response to posture and subtle cardiac dysfunction as the pathophysiological changes underlying the sodium retention.

In the past 5 years, I was able to document subtle increases in the intra-renal activity of the renin-angiotensin system as the first pathophysiological change that pre-dispose pre-ascitic cirrhotic patients to a sodium retention tendency. This led to my next study which assessed the effects of an angiotensin II receptor antagonist, losartan, on the renal sodium excretion in these patients and was able to show an increase in sodium excretion with an acute dose of losartan.

More recently, using intravenous calcium as a probe, I have been able to identify the loop of Henle as one of the sites of sodium retention in cirrhosis, in addition to the proximal and distal convoluted tubules of the nephron. This has the therapeutic potential of using calcium as a treatment for sodium retention in cirrhosis.

My current research theme is to assess the contribution of myocardial dysfunction in the pathogenesis of sodium retention in cirrhosis.

I have shown that cirrhotic patients have both systolic and diastolic dysfunction, and that the dysfunction is associated with sodium retention and an inability to perform work. That is, these patients are unable to increase their cardiac output for a given amount of physical work. Their oxygen consumption is reduced. As a result, they have a lower anaerobic threshold with metabolic consequences.

One of the potential mechanisms is an activated sympathetic nervous system which can cause both diastolic and systolic dysfunction. My next project is to assess the effects of a beta-blocker in improving myocardial performance, and hence work performance. This will be followed by blockers of other putative mediators, such as an angiotensin II receptor antagonist, antibodies to cytokines, etc. The ultimate goal of all these research is to find the reason for sodium retention and institute both prophylactic and therapeutic measures.

The use of a vasopressin V2 receptor antagonist to increase free water clearance in cirrhotic patients with ascites has been shown not only to correct hyponatremia; it has also been shown to decrease the frequency of paracentesis in those patients who require frequent paracenteses. I am one of a handful of Canadian investigators who are currently involved in the international multicentre trial of the long-term use of vasopressin V2 receptor antagonist in the management of ascites.

My other area of research is to elucidate the pathophysiology of hepatorenal syndrome, a dreaded complication of ascites. I have a CIHR funded project to assess the use of albumin dialysis as a treatment for hepatorenal syndrome. The rationale is to use albumin dialysis to remove toxins that are not metabolized by the failing liver, in order to improve systemic hemodynamics and renal perfusion. I have also received funding from the Canadian Liver Foundation to study the use of terlipressin, a systemic vasoconstrictor, as a treatment for hepatorenal syndrome. Terlipressin is being used to improve systemic hemodynamics and hence renal perfusion. Ongoing projects include the use of systemic vasoconstrictors to prevent the development of hepatorenal syndrome associated with infection.

Am J Gastroenterol. 2018 Jun 08;:
Bajaj JS, Tandon P, O'Leary JG, Biggins SW, Wong F, Kamath PS, Garcia-Tsao G, Maliakkal B, Lai JC, Fallon M, Thuluvath P, Vargas HE, Subramanian RM, Thacker LR, Reddy KR
Hepatology. 2018 Apr 24;:
Bajaj JS, Moreau R, Kamath PS, Vargas HE, Arroyo V, Reddy KR, Szabo G, Tandon P, Olson J, Karvellas C, Gustot T, Lai JC, Wong F
Hepatology. 2018 Apr 16;:
O'Leary JG, Reddy KR, Wong F, Garcia-Tsao G, Kamath PS, Bajaj JS
Liver Int. 2018 Mar 13;:
Wong F, Jepsen P, Watson H, Vilstrup H
Hepatology. 2018 Jan 08;:
O'Leary JG, Reddy KR, Garcia-Tsao G, Biggins SW, Wong F, Fallon MB, Subramanian RM, Kamath PS, Thuluvath P, Vargas HE, Maliakkal B, Tandon P, Lai J, Thacker LR, Bajaj JS
Am J Gastroenterol. 2017 Dec 19;:
Bajaj JS, Rajender Reddy K, Tandon P, Wong F, Kamath PS, Biggins SW, Garcia-Tsao G, Fallon M, Maliakkal B, Lai J, Vargas HE, Subramanian RM, Thuluvath P, Thacker LR, O'Leary JG
Cancer. 2017 Nov 07;:
Armenian SH, Mertens L, Slorach C, Venkataraman K, Mascarenhas K, Nathwani N, Wong FL, Forman SJ, Bhatia S
Aliment Pharmacol Ther. 2017 Oct 09;:
Bhutta AQ, Garcia-Tsao G, Reddy KR, Tandon P, Wong F, O'Leary JG, Acharya C, Banerjee D, Abraldes JG, Jones TM, Shaw J, Deng Y, Ciarleglio M, Bajaj JS
Am J Gastroenterol. 2017 Apr 25;:
Wong F, O'Leary JG, Reddy KR, Garcia-Tsao G, Fallon MB, Biggins SW, Subramanian RM, Thuluvath PJ, Kamath PS, Patton H, Maliakkal B, Tandon P, Vargas H, Thacker L, Bajaj JS



Professor, Division of Gastroenterology, Faculty of Medicine, University of Toronto