title: Regulation of renal sodium and water excretion in the nephrotic syndrome and cirrhosis of the liver.
abstract: Atrial natriuretic peptide (ANP) produced in the heart and prostaglandin E2 (PGE2) synthesised in the kidneys facilitate renal excretion of sodium and water, and thus oppose the actions of angiotensin II, aldosterone, arginine vasopressin (AVP), endothelin, and the renal sympathetic nerves. In the present work we studied the contributions and interactions of these substances in the regulation of blood volume (BV), renal haemodynamics, renal sodium and water handling and blood pressure (BP) in patients with glomerulonephritis and cirrhosis. The aim was through a better understanding of the pathophysiology to improve the treatment of fluid retention in these patients, which occurs as development of the nephrotic syndrome and accumulation of ascites, respectively. Normotensive patients with glomerulonephritis but without the nephrotic syndrome had normal baseline BV values measured as the sum of plasma volume and red cell volume; they responded to BV expansion after infusion of albumin and BV depletion after administration of furosemide with appropriate counterregulatory hormonal changes. However, they tended to hold more fluid within the intravascular phase after both manipulations than did the healthy subjects. The acutely induced increase in BV did not affect the BP, which was likely attributable to the changes in plasma values of angiotensin II and ANP shown. ANP could be expected to be a tool in the management of fluid accumulation in patients with the nephrotic syndrome and cirrhosis. The non-renal effects of high-dose ANP were studied for the first time in dialysis patients without excretory kidney function. A reversible shift of fluid away from the intravascular phase was demonstrated. The BV was maximally reduced 30 min after ANP had been given. The BP was reduced before fluid displacement occurred and to the same extent in patients and healthy subjects. The reduction in the BV was negatively correlated to the reduction in BP. From that study it is inferred that the BP reducing effect of ANP is not mediated by its diuretic effect or ability to displace fluid from the intravascular to the interstitial fluid compartment. As a pharmacological dose of ANP was given, it can only be suggested that endogenous ANP, by altering transcapillary Starling mechanisms, assists in buffering intravascular fluid expansion until renal excretion or dialysis can take place. The same dose of ANP was given to patients with the nephrotic syndrome and cirrhosis. The ability of ANP to increase sodium excretion through inhibition of sodium reabsorption in the distal tubules and to increase the glomerular filtration rate (GFR) was blunted in both patient groups, but the BP was reduced to the same extent as in the healthy controls. Patients with the nephrotic syndrome tended to have a slightly elevated BP. We only studied patients with normal or slightly reduced GFR. They had a normal BV, reduced renal filtration fraction, suppressed aldosterone, increased ANP, but normal plasma values of angiotensin II, endothelin, and AVP, and normal urinary excretion of PGE2. Thus, neither haemodynamic nor hormonal factors can easily explain the spontaneous sodium retention or the resistance to the effects of ANP and furosemide. An interesting finding, not previously reported in nephrotic humans, was the low cyclic guanosine 3'5'-monophosphate (cGMP) in plasma and urine in relation to ANP, both before and after administration of ANP. It is hypothesised that renal resistance to ANP, exaggerated renal cGMP degradation, or preponderance of clearance receptors in nephrotic kidneys may contribute to sodium retention and the low filtration fraction. Elevation of ANP in these patients is connected with increased albuminuria, and probably an increase in intraglomerular capillary pressure. The resistance to furosemide could not be attributed to delayed passage of fluid from the interstitial to the intravascular fluid phase, but is most likely due to renal tubular resistan
authors.affiliation: Department of Nephrology and Medicine, Aarhus Kommunehospital.
authors.forename: B
authors.initials: B
authors.lastname: Jespersen
mesh_terms: D001834:Body Water / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008094:Lithium / Q000493:pharmacokinetics; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008657:Metabolic Clearance Rate; D009318:Natriuresis / Q000502:physiology*; D009404:Nephrotic Syndrome / Q000503:physiopathology*; D012079:Renal Circulation / Q000502:physiology*
chemical_list: D008094:Lithium