Effect of Atrial Natriuretic Peptide on Urine Flow and Glomerular Filtration During Acute Renal Allograft Rejection

Abstract

The effect of exogenous atrial natriuretic peptide (ANP) on urine excretion and glomerular filtration rate (GFR) during acute renal allograft rejection was evaluated in a canine model. Eight animals underwent simultaneous allotransplantation and unilateral native nephrectomy. No pre-operative or postoperative immunosuppressive therapy was given. Acute renal function studies were performed on the allografts and companion, native kidneys following surgical exposure and mobilization on the third postoperative day. At reexploration, the allografts were found to be grossly enlarged (138 ± 10 gm.) and contained moderate-to-marked perivascular interstitial infiltration. Glomerular filtration rate, determined by measurement of urinary inulin clearance, was significantly reduced from prenephrectomy baseline values (19 ± 4 ml. per minute versus 32 ± 5 ml. per minute, p <.05). During a 30 minute, intravenous ANP infusion, allograft urine flow rates increased from 1.4 ± 0.5 ml. per minute to 3.3 ± 0.4 ml. per minute (p <.01), and GFR increased from 19 ± 4 ml. per minute to 24 ± 4 ml. per minute (p <.05). During ANP infusion, mean arterial pressure declined from 136 ± 7 mm. Hg to 116 ± 7 mm. Hg (p <.05), and the hematocrit remained unchanged. These observations are consistent with previously described, ameliorative effects of ANP in other models of acute ischemic renal injury and provide an experimental basis for more extended studies examining the potential usefulness of ANP as adjunctive therapy in the treatment of acute renal allograft rejection.