Endogenous ANP in postischemic acute renal allograft failure.
Circulating atrial natriuretic peptide (ANP) levels and glomerular binding sites for ANP were examined in 23 subjects undergoing renal transplantation. Subjects were divided into two groups, group 1 (n = 12) with prompt and group 2 (n = 11) with delayed allograft function. Sixty to 180 min after graft reperfusion, renovascular resistance was threefold higher and glomerular filtration rate (GFR) depressed by 79% in group 2 vs. group 1. Corresponding median plasma ANP (114 vs. 140 pg/ml) and guanosine 3',5'-cyclic monophosphate (cGMP) levels (22 vs. 28 pmol/ml) were similarly elevated in the two groups [P = not significant (NS)]. Autoradiographic analysis of glomeruli in an allograft biopsy revealed the median density of total receptors (24 vs. 28 fmol/mm3), A receptors (15 vs. 19 fmol/mm3), and C receptors (6 vs. 9 fmol/mm3) for ANP to also be similar in group 2 vs. group 1, respectively (P = NS). By postoperative day 3, allograft GFR averaged only 6 +/- 2 in group 2 vs. 59 +/- 4 ml/min in group 1. Median plasma ANP levels doubled in each group to 262 and 251 pg/ml, respectively (P = NS). However, median values for plasma levels (38 vs. 17 pmol/ml) and the fractional clearance of cGMP (1.9 vs. 1.2) were significantly higher in group 2 than group 1. We conclude that, despite an adequate density of glomerular ANP receptors and enhanced cGMP generation, neither renal vasoconstriction nor hypofiltration is alleviated by a progressive elevation of plasma ANP levels in renal transplant recipients with sustained postischemic injury. We infer that constricted afferent arterioles are unresponsive to the vasorelaxant action of endogenous ANP in this form of postischemic, acute renal failure.
Vinot
O
O
Division of Nephrology, Stanford University School of Medicine, California 94305-5114, USA.
Bialek
J
J
Canaan-Kühl
S
S
Scandling
J D
JD
Dafoe
D
D
Alfrey
E
E
Myers
B D
BD
D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001345:Autoradiography; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011184:Postoperative Period; D012079:Renal Circulation; D013997:Time Factors; D014655:Vascular Resistance
D009320:Atrial Natriuretic Factor