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Hepatorenal Syndrome: A Death Sentence?
Hepatorenal Syndrome (HRS) is any renal failure (elevation of serum creatinine over 1,5 mg/dL or 24-hour creatinine clearance of less than 40%) that does not improve with the administration of up to 1,5 liters of plasma expanders that is concomitant with chronic hepatic disease, in the absence of parenchymal renal disease, obstructive uropathy, proteinuria of more than 500mg/d, shock of any kind, nephrotoxic drugs or fluid losses. It has a prevalence of 40% among cirrhotic patients and its mortality, if not treated, is 90% within 2 weeks and the 10% left die within 3 to 6 months of onset. The only effective treatment to date is liver transplant, but the rapid progression of this syndrome usually denies this possibility. However, there are new treatment options that can revert this syndrome and help these patients. Pathophysiology: There are many theories that try to explain the relation between liver and kidney, but the most widely accepted theory involves a disbalance of humoral and local vasoconstrictor and vasodilator factors on different vascular territories. On the kidney, the action of vasoconstrictors such as renin, angiotensin, adenosine and endothelin predominates over the local vasodilators such as Nitric Oxide (NO) and Prostaglandins. This disbalance produces a reduction in glomerular filtration rate (GFR) and renal plasma flow (RPF) which in turn translates into fluid retention and uremia. And could also lead to Acute Tubular Necrosis (ATN). On the splanchnic vessels the tendency is different, with arteriolar vasodilation as a consequence of the predominant action of local Nitric Oxide over endothelin and vasopressin, renin and angiotensin (because comparatively this vessels have less receptors for these vasoconstrictors and are more sensitive to NO). This in turns translates into a diversion of blood flow to the splanchnic regions. Peripheral vascular resistances are raised, but cannot compete with the lower resistance of the splanchnic regions resulting in a reduced total systemic vascular resistance. If we factor in the presence of a third space (because of portal hypertension and hypoproteinemia) that reduces the effective plasma volume then the whole equation of vasoconstriction of renal arteries, the diverted flow to the splanchnic region and reduced plasma volume means a HUGE reduction of Renal Plasma Flow and Glomerular Filtration Rate. New treatments target this pathophysiology and promising drugs have been tested:Lets consider their goals: Vasoconstrictors that target the splanchnic vessels: Midodrine (an alpha adrenergic agonist), Octreotide (a somatostatine analog) and Terlipressin (a vasopressin analog). The goal is to push the blood from these vessels to the kidney, brain and muscles. Aggressive plasma expansion with albumin and crystalloid solutions in order to restore plasma volume and raise the level of serum proteins to reduce edema and ascites (third spaces). This ensures that there will be enough plasma to feed renal circulation. A novel approach with a currently unknown mechanism of action is the use a N-Acetylcysteine which in intravenous treatment has been reported to have a 67% rate of improvement of renal function.The combination of these treatments could lead to 65% to 75% survival rates.
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