The effect of α-human atrial natriuretic peptide on the incidence of acute renal failure in cadaveric kidney transplantation

Abstract

In previous studies in humans, mannitol (20%, 250 ml) has been shown to reduce the incidence of acute renal failure (ARF) after transplantation from 54% to 19%. In rats, atrial natriuretic peptide appears to prevent ischemia-induced ARF. We therefore decided to evaluate the effects of alpha-human atrial natriuretic peptide (alpha-h-ANP) both alone and combined with mannitol during transplantation in humans. First, we demonstrated that systemic alpha-h-ANP infusion during kidney transplantation was safe in dosages up to 0.08 micrograms/kg per minute. In these patients the calculated metabolic clearance rate of alpha-h-ANP was relatively low ranging from 0.68 to 1.80 l/min. In a second study of 11 renal graft recipients, no mannitol was used and alpha-h-ANP (0.05 micrograms/kg per minute) was infused into the donor kidney artery during transplantation for 46 +/- 2 min, followed by IV administration for 71 +/- 2 min. Our aim was to reduce the incidence of ARF. Nevertheless, ARF occurred immediately after surgery in four of the patients (36%) in this group and, as a result, mannitol was reintroduced. A third group of nine renal graft recipients received alpha-h-ANP (total dose 400 micrograms) as five IV injections within 90 min after transplantation. ARF occurred in four of these patients (44%). We conclude that alpha-h-ANP, administered according to the aforementioned protocols in such small groups of patients, does not seem to be of value in the prevention of ARF after transplantation.

Atrial natriuretic factor: a protective role after acute renal ischemia?: Is there room for it in kidney transplantation?*

“…The results of all the aforementioned experiments are interesting, but it is also clear that ANF is not always able to reverse the renal function of the oligoanuric kidney when it is already in the maintenance phase of acute AFW [4,62]. This fact reinforces the necessity of using ANF just before declamping and secondarily with a continuous infusion of very low doses for several days.…”

Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy

“…Several clinical studies have been carried out to clarify its role in patients with chronic renal failure, especially in relation to their fluid state [l, 4,13-15,18,21-231. Investigations have also been performed in renal transplant patients [4,16,20,24] relating levels of endogenous or synthetic ANF to renal function. The present study was performed in patients on chronic hemodialysis undergoing transplantation with kidneys from living related donors.…”

Atrial Natriuretic Factors: The Treatment of the Future or a False Hope?

“…As mentioned above, several animal studies have suggested that AN'P has a protective effect against reperfusion injury in the transplanted kidney (ta ble 2). In contrast, exogenous ANP did not im prove graft function in three separate studies ex amining transplanted human kidneys, although the number of patients in these studies was quite small [Ratcliffe et al" 1991;Sands et al, 1991;Smits et al, 1989). Perhaps more importantly, however.…”

“…These authors suggested that since anatomical and function damage had already oc curred in their patients, any benefit of ANP in severe ARF would require early administration of the peptide. Sands et al [1991] human negative Smits et al [1989] human negative…”