Atrial natriuretic peptide in ischaemic acute renal failure

Abstract

Acute renal failure (ARF) is associated with increased morbidity and mortality rates. The need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery. Human atrial natriuretic peptide (h-ANP) is a potent endogenous natriuretic and diuretic substance. The exogenous administration of h-ANP increases the glomerular filtration rate (GFR) and renal blood flow (RBF) in clinical acute renal failure.Aim: To study the effects of the long-term infusion of h-ANP on GFR, RBF and renal outcome in patients with ischaemic ARF. To investigate the effects of h-ANP and furosemide on GFR, RBF and renal oxygen consumption (RVO2). To validate two independent methods, the renal vein thermodilution and the infusion clearance technique for bedside estimation of absolute RBF and GFR in the intensive care unit without the use of urine collection.Methods: Renal tolerance to h-ANP was evaluated in 11 patients with ARF treated with h-ANP infusion (50 ng · kg-1·min-1) for at least 48 hours. h-ANP was abruptly discontinued and again re-instituted. Sixty-three patients with ischaemic ARF were randomised to either placebo or continuous infusion of h-ANP. Treatment with h-ANP/placebo continued until serum creatinine was reduced to below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis. The effects of h-ANP (n=10) and furosemide (n=9) on GFR, renal haemodynamics and RVO2 were studied in cardiac surgery patients, with normal renal function, using the infusion clearance technique. Results: The discontinuation of long-term h-ANP infusion reduced urine flow, GFR and RBF. These variables were normalised when h-ANP treatment was re-instituted. Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group required dialysis before or at day 21 (p=0.009). Eight (28%) patients in the h-ANP group compared with 17 (57%) in the placebo group suffered from the combined end point dialysis or death before or at day 21 (p=0.017). The reproducibility was highest for the infusion clearance technique, which also had the highest agreement with the reference method (urinary clearance). h-ANP caused an increase in GFR (12%), sodium re-absorption (9%) and RVO2 (21-31%), while furosemide reduced GFR (12%), sodium re-absorption (26-31%) and RVO2 (18-29%). For both ANP and furosemide, changes in GFR correlated strongly to RVO2.Conclusions: No renal tolerance develops during the long-term infusion of h-ANP. The infusion of h-ANP reduces the probability of dialysis and improves dialysis-free survival in early, ischaemic ARF after complicated cardiac surgery. The infusion clearance method is superior to the renal vein thermodilution technique for estimating total RBF and GFR in ICU. The strong correlation between GFR and RVO2 underscores the importance of GFR and the filtered tubular load of sodium as a major determinant of RVO2.