Renal dysfunction increasing blood flow

Minoxidil (loniten) is efficacious in patients with the most severe and drug-resistant forms of hypertension. A small fraction of minoxidil is metabolized by hepatic sulfotransferase to the active molecule, minoxidil N-O sulfate. Minoxidil sulfate activates the ATP-modulated channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle. Minoxidil produces arteriolar vasodilation with essentially no effect on capacitance vessels. Minoxidil preferentially increases blood flow to skin, skeletal muscle, the GI tract, and the heart. The disproportionate increase in blood flow to the heart may have a metabolic basis, in that administration of minoxidil is associated with a reflex increase in myocardial contractility and in cardiac output. The cardiac output can increase by as much as three- to fourfold, primarily due to enhanced venous return to the heart. The increased venous return probably results from enhanced flow in vascular beds with a fast response for venous return to the heart. The adrenergic increase in myocardial contractility contributes to the increased cardiac output, but is not the predominant factor. The renal effects of minoxidil are complex it dilates renal arteries, but systemic hypotension produced by the drug actually can decrease renal blood flow. Renal function usually improves in patients who take minoxidil for the treatment of hypertension, especially if renal dysfunction is secondary to hypertension. Minoxidil potently stimulates renin secretion, an effect mediated by renal sympathetic stimulation. 

Both urea and creatinine will be elevated with renal injury, and the elevations in both are usually proportional. Calculation of the ureaxreatinine ratio may implicate extrarenal causes for the analyte elevations (see Limitations of the Method , below). Extremely high ureaxreatinine when both are elevated (where urea is elevated markedly out of proportion to creatinine) indicates decreased renal blood flow, urinary tract obstruction or extravasation of urine into the peritoneal cavity. Elevation in the ureaxreatinine ratio as a consequence of pure urea elevation implicates gastrointestinal hemorrhage, high protein diet, increased protein catabolism, or loss of muscle mass. A decreased ratio indicates primary liver dysfunction (due... 

Endotoxinaemia Different degrees of endotoxinaemia are often detectable in patients suffering from severe liver disease as a result of restricted hepatic endotoxin clearance. There is a correlation between endotoxinaemia and renal dysfunction, and renal blood flow is reduced. Nitrogen monoxide is also released. By reducing endotoxinaemia (after treatment with polymyxin B, for example), the diminished functional activity of the kidney improves and diuresis as well as natriuresis increase, (s. tab. 16.5)... 

Functional renal insufficiency is manifested as increases in serum creatinine and blood urea nitrogen. As cardiac output and renal blood flow decline, renal perfusion is maintained by the vasoconstrictor effect of angiotensin II on the efferent arteriole. Patients most dependent on this system for maintenance of renal perfusion (and therefore most likely to develop functional renal insufficiency with ACE inhibitors) are those with severe heart failure, hypotension, hyponatremia, volume depletion, and concomitant use of NSAIDs. - Sodium depletion (usually secondary to diuretic therapy) is the most important factor in the development of functional renal insufficiency with ACE inhibitor therapy. Renal insufficiency therefore can be minimized in many cases by reduction in diuretic dosage or liberalization of sodium intake. In some patients, the serum creatinine concentration will return to baseline levels without a reduction in ACE inhibitor dose. Since renal dysfunction with ACE inhibitors is secondary to alterations in renal hemodynamics, it is almost always reversible on discontinuation of the drug. ... 

Creatinine is a product of the degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Plasma creatinine is dependent on muscle mass and can be lowered in severe myopathy. Although plasma levels are less affected by diet compared to urea, malnutrition may lower plasma creatinine (Evans 1987 Braun, Lefebvre, and Watson 2003). Plasma creatinine is normally filtered from the plasma, and it is reabsorbed and secreted by the proximal tubules to a minor extent, although secretion is higher in rodents compared to humans. Elevated plasma creatinine is a reliable indicator of impaired glomerular filtration or alterations in renal blood flow, but severe tubular dysfunction can also increase plasma creatinine. 

Microalbuminuria in healthy subjects is associated with atherosclerotic risk factors such as increased systolic and diastolic blood pressure (BP) decreased Apo A1 and HDL-C levels (12). Minor derangements of renal function are associated with an increase in CVD risk factors and promote progression of atherosclerosis (reviewed in ref. 14). However, in a separate study in contrast to BP, body mass index (BMl), and triglycerides (TGs), there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. This suggests that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric but otherwise healthy subjects (75). 

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