Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function

Abstract

Thirty-eight recipients of nineteen pairs of cadaveric kidneys were entered into a double-blind randomized study in which one recipient received a 12-hour intravenous infusion of Atriopeptin III (AP-3), a synthetic analogue of atrial natriuretic factor, commencing at release of the vascular clamps, and the other received a placebo infusion. In an initial dose ranging study, successive groups of six kidneys (3 pairs) were randomized to receive each of 0.0125, 0.025, 0.05 micrograms/kg/min AP-3 or placebo. Thereafter 20 kidneys (10 pairs) received 0.1 micrograms/kg/min or placebo. There was no discernable effect of AP-3 on allograft creatinine clearance or sodium excretion either when the highest dose of AP-3 was considered alone or when all doses were considered together. Averaged creatinine clearance over the period 0 to 24 hours after transplantation was 20.1 +/- 14.7 ml/min in patients receiving active treatment and 18.2 +/- 13.7 ml/min in those receiving placebo. Thus, despite the documentation of a protective effect of atrial natriuretic factor in animal models of renal ischemia, it is unlikely that intravenous infusion of AP-3 in this dose range will be of benefit in improving immediate renal allograft graft function.

Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy.

“…It is likely that cyclic GMP, a second messenger induced by NO, is elaborated by the kidney during IL-2 therapy (68,73,74). It has been shown that atrial natriuretic factor, a peptide with vasodilating and diuretic/natriuretic properties, ameliorates, via cyclic GMP, the severity of acute renal failure (75,76).…”

Natriuretic Peptides in the Management of Solid Organ Transplantation Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis

“…A total of 18 studies were further excluded, since they involved evaluation in nonsolid organ transplant setting. Our analysis finally identified 7 eligible studies comprising total 238 participants (118 natriuretic peptide group; 120 control group) [4, 6, 22–26]. Characteristics of the included studies are summarized in Table 1.…”

“…Mean age of the participants was 44 years and 40% participants were females. Four studies (135 participants) evaluated the role of human atrial natriuretic peptide [4, 6, 23, 26]. Three studies (103 participants) evaluated the role of urodilatin [22, 24, 25].…”

“…Despite the above described physiologic actions and potential to reverse multiple factors involved in the pathogenesis of solid organ transplantation associated AKI (including renal ischemia and hyperactivated renin-angiotensin-aldosterone system), randomized controlled trials (RCTs) evaluating the role of natriuretic peptides in this setting have been largely underpowered and have produced conflicting results [4, 6, 22–26]. In addition, natriuretic peptides, especially at high doses, are known to cause hypotension and arrhythmias, complications that can potentially negate the possible benefits [14–17, 27].…”

Section 3: Prevention and Treatment of AKI

“…There have been several negative studies of prophylactic ANP therapy; for example, ANP failed in two studies to prevent primary renal transplant dysfunction 228, 229 and ANP prophylaxis also failed to prevent CI-AKI. 230 Based on the positive results of small clinical studies using ANP to treat AKI, a randomized placebo-controlled trial in 504 critically ill patients with AKI was conducted.…”