The underfill theory involves activation of the renin–angiotensin–aldosterone system, which leads to an increase in absorption of sodium from the kidney tubule (termed renal sodium avidity) mediated by aldosterone, which acts on mineralocorticoid receptors in the distal convoluted tubule. This is believed to be a key step in the pathogenesis of ascites in cirrhotics as well. It has been hypothesized that the progression from ascites to hepatorenal syndrome is a spectrum where splanchnic vasodilation defines both resistance to diuretic medications in ascites (which is commonly seen in type 2 HRS) and the onset of kidney vasoconstriction (as described above) leading to hepatorenal syndrome. Prevention
The risk of death in hepatorenal syndrome is very high; consequently, there is a significant emphasis on the identification of patients who are at risk for HRS, and prevention of triggers for onset of HRS. As infection (specifically spontaneous bacterial peritonitis) and gastrointestinal hemorrhage are both complications in individuals with cirrhosis, and are common triggers for HRS, specific care is made in early identification and treatment of cirrhotics with these complications  to prevent HRS. Some of the triggers for HRS are induced by treatment of ascites and can be preventable. The aggressive use of diuretic medications should be avoided. In addition, many medications that are either used to treat cirrhotic complications (such as some antibiotics) or other conditions may cause sufficient impairment in kidney function in the cirrhotic to lead to HRS.
Nisoldipine is a pharmaceutical drug used for the treatment of chronic angina pectoris and hypertension. It is a calcium channel blocker of the dihydropyridine class. It is sold in the United States under the proprietary name Sular. Nisoldipine has tropism for cardiac blood vessels.It was patented in 1975 and approved for medical use in 1990. Contraindications
Nisoldipine is contraindicated in people with cardiogenic shock, unstable angina, myocardial infarction, and during pregnancy and lactation. Adverse effects
Common side effects are headache, confusion, fast heartbeat, and edema. Hypersensitivity reactions are rare and include angioedema. Interactions
The substance is metabolized by the liver enzyme CYP3A4. Consequently, CYP3A4 inducers such as rifampicin or carbamazepine could reduce the effectiveness of nisoldipine, while CYP3A4 inhibitors such as ketoconazole increase the amount of nisoldipine in the body more than 20-fold. Grapefruit juice also increases nisoldipine concentrations by inhibiting CYP3A4. Pharmacology
Mechanism of action
Nisoldipine is a calcium channel blocker that selectively inhibits L-type calcium channels. References
External links
Diseases Database (DDB): 30009
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