Natriuretic Peptides

Exogenous administration of ANP or its analog anaritide decreases systemic blood pressure through arterial and venous dilation. Nesiritide (human recombinant BNP), the only natriuretic peptide thus far approved by the Food and Drug Administration (FDA) for exogenous administration, is effective in the parenteral treatment of end-stage congestive heart failure. Its use promotes diuresis and relieves symptoms related to pulmonary congestion and edema. Urodilatin, an ANP congener produced by the kidney and excreted in urine, lacks the systemic vasodilator effects of the parent compound but has similar action on renal function.

Considerable interest has arisen regarding the ability of infused ANP to reverse established acute renal failure ("renal rescue"). Animal studies of both ischemic^[84] and nephrotoxic^[85] acute tubular necrosis have demonstrated that ANP infusion improves RBF and GFR, induces natriuresis, and decreases azotemia and renal histologic damage. In a controlled pilot study^[86] involving 53 patients with established intrinsic acute renal failure, ANP infusion doubled creatinine clearance from 10 to 21 mL/min in 24 hours and decreased the incidence of dialysis from 52% to 23% (P < .05).

These results generated a large randomized, controlled, multicenter study in which 504 patients were prospectively identified as having oliguric (urine output, <400 mL/day) or nonoliguric acute tubular necrosis and randomized to receive anaritide or placebo for 24 hours.^[87] In patients with oliguric acute renal failure, anaritide infusion induced significantly greater dialysis-free survival than placebo did, 27% versus 8% (P < .008). However, in nonoliguric acute renal failure, anaritide actually appeared to worsen survival (48% versus 59% with placebo). Of note, anaritide induced a decrease in blood pressure and urine flow rate in nonoliguric patients, whereas in oliguric patients, blood pressure was less affected and the urine flow rate increased.

To further evaluate these findings, the study was repeated in a multicenter, randomized, double-blind, placebo-controlled trial of 222 patients with oliguric acute renal failure.^[88] No differences were noted in dialysis requirement, dialysis-free survival, or 60-day mortality between anaritide and placebo. However, patients receiving anaritide had significantly more hypotension during infusion of the study drug.

These studies emphasize the difficulty of translating promise in animal studies to successful outcome in large clinical trials and also emphasize the importance of maintenance of renal perfusion pressure in acute renal failure, given the loss of renal autoregulation that occurs.^[8]