Restoration of Renal Responsiveness to Atrial Natriuretic Peptide in Experimental Nephrotic Syndrome by Albumin Infusion

Abstract

Background: The natriuretic/diuretic response to atrial natriuretic peptide (ANP), an important regulator of water and Na⁺ balance, is markedly attenuated in nephrotic syndrome (NS). It has been suggested that the diminished renal responsiveness to ANP may contribute to the pathogenesis of salt retention and edema formation in NS. However, the mechanisms underlying the renal hyporesponsiveness to ANP remain largely unknown. Methods: The acute effects of exogenous infusion of ANP (5 µg/kg + 10 µg/kg/h) were studied by clearance methodology in control rats, hypoalbuminemic rats with Adriamycin (ADR)-induced NS and in ADR-treated rats infused with hyperoncotic albumin sufficient to restore plasma albumin to normal levels. Results: Administration of ANP to control rats resulted in a significant increase in urinary flow rate, absolute rate of sodium excretion (+456%) and glomerular filtration rate (GFR). Mean arterial blood pressure decreased following infusion of the peptide. In the nephrotic rats, baseline GFR and Na⁺ excretion were significantly lower than in the control animals, and the renal effects of ANP were markedly blunt compared to the control animals. In contrast, the hypotensive effect of ANP in the ADR-treated rats was largely preserved. Infusion of hyperoncotic albumin prior to ANP administration reversed the decrease in baseline GFR and Na⁺ excretion and completely restored the renal effects of ANP in the nephrotic rats. Conclusion: These findings indicate that renal hyporesponsiveness to ANP in rats with ADR-induced NS is a reversible phenomenon that appears to be of functional origin rather than reflecting permanent cellular damage.

Edema in childhood nephrotic syndrome: possible genes–hormones interplay

“…In NS, resistance to serum ANP is an observation in experimental animals and humans [ 17 , 18 ], these studies showed that ANP levels were frequently elevated in INS children than in healthy or remission children. Restoration of renal receptiveness to ANP in animal models of NS by albumin infusion indicates that renal hypo-responsiveness to ANP is a reversible functional condition rather than permanent cellular damage [ 19 ]. Moreover, Cataliotti et al observed increased plasma ANP concentration that frequently correlated with the edema severity [ 20 ].…”

Observation of effect of continuous intravenous drip of low molecular dextran combined with furosemide in the treatment of edema in children with nephrotic syndrome

“…Glucocorticoid is a common treatment means, and most children can be cured, but there are also some children who are insensitive to glucocorticoid, so the disease relapses and the healing is delayed, finally developing into refractory nephropathy, affecting the healthy growth and development of children [5,6]. Factors affecting the prognosis of NS in children include the long-term repeated edema.…”

L-Citrulline Protects against Rhabdomyolysis -Induced Acute Renal Failure in Rats

“…The striated muscle dissolved because of the intramuscular injection of glycerol, the myoglobin and other potentially toxic intracellular components released into the systemic circulation. The mechanisms of glycerol-induced myoglobinuric ARF are renal vasoconstriction and congestion, ischaemia, and myoglobin induced cytotoxicity [2,3]. Moreover, there is growing evidence indicating that the reactive oxygen species (ROS) plays an important role in the pathogenesis of myoglobinuric ARF, oxidative stress would participate in the tubular necrosis favoring lipid peroxidation of cellular membranes [1,4].…”