Endogenous anp in postischemic, acute renal allograft failure.
Vinot, Olivier, Joan Bialek, Sima Canaan-Kuhl, John D. Scandling, Donald
Dafoe, Edward Alfrey, Bryan D. Myers
Division of Nephrology, Stanford University School of Medicine,
Stanford, California, Department of Surgery, Stanford University
School of Medicine, Stanford, California
APStracts 2:0032F, 1995.
Circulating ANP levels and glomerular binding sites for ANP were
examined in 23 subjects undergoing renal transplantation. Subjects
were divided into group 1 (N=12) with prompt and group 2 (N=11) with
delayed allograft function. Sixty-180 minutes after graft
reperfusion, renovascular resistance was 3-fold higher and GFR
depressed by 79% in group 2 vs group 1. Corresponding median plasma
ANP ( 114 vs 140 pg/ml) and cGMP levels (22 vs 28 p mol/ml) were
similarly elevated in the two groups (p=NS). Autoradiographic
analysis of glomeruli in an allograft biopsy revealed the median
density of total receptors (24 vs 28), A receptors (15 vs 19) 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
are 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.
Received 28 December 1994; accepted in final form 28 February
1995.
APS Manuscript Number F461-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.