Raised plasma levels of atrial natriuretic factor in cardiac allograft recipients: evidence of increased cardiac secretion and decreased renal clearance

The mechanism(s) causing high levels of plasma atrial natriuretic factor (ANF) in cardiac allograft recipients is(are) unclear. The kidney is important for the clearance of ANF and renal function may decline with cyclosporin A therapy in these patients. The relationship between plasma ANF level and renal function and also the pharmacokinetics of a continuous infusion of ANF (15.5 ng.kg^-1.min^-1 for 60 min) was examined in 6 cardiac allograft recipients on cyclosporin A therapy. Resting plasma ANF levels were significantly higher in these patients than in 8 healthy subjects (71 vs. 21 ng.l^-1). Both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were significantly lower in these patients than in healthy subjects (215 vs. 617 ml.min^-1 and 55 vs. 102 ml.min^-1 respectively). There was a significant inverse correlation between plasma ANF and ERPF (r = -0.86) and between plasma ANF and GFR (r = -0.81). During the period of ANF infusion, steady state plasma ANF levels were significantly higher in cardiac allograft recipients. Total body clearance of ANF was marginally lower in these patients than in healthy subjects (60 vs. 10.0 l.min^-1) although this difference did not reach statistical significance. Derived endogenous secretion rate of ANF was threefold higher in patients when compared to healthy subjects (633 vs. 208 ng.min^-1). We have therefore shown that cardiac allograft recipients on cyclosporin A have elevated plasma ANF levels and also decreased renal function. Pharmacokinetic analysis have shown that this increase in plasma ANF levels is due more to increased ANF secretion than to decreased ANF clearance in these patients.