Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.
BACKGROUND
Acute renal failure is a frequent complication following orthotopic hepatic transplantation. A reduction in the synthesis of intrarenal vasodilator prostaglandins has been proposed as having an important role in the pathogenesis of renal insufficiency associated with hepatic dysfunction, as well as in the nephrotoxicity associated with cyclosporine and FK506 immunosuppressive therapy. Therefore, administration of vasodilator prostaglandins may improve renal function following hepatic transplantation. This study was designed to determine the effect of continuous intravenous alprostadil (prostaglandin E1) on postoperative renal function in hepatic transplant patients.


METHODS
In a randomized, double-blind, placebo-controlled trial, 21 patients who had undergone orthotopic hepatic transplantation and had a measured postoperative glomerular filtration rate (GFR) of less that 50 mL/minute received intravenous alprostadil at 0.6 microgram/kg/hour or placebo for five days. Glomerular filtration rate and effective renal plasma flow (ERPF) were measured by a single-injection clearance method using a radionuclide agent in 53 patients within 12 hours after admission to our surgical intensive care unit. Usual postoperative care was not modified. Radionuclide GFR and ERPF measurements were repeated on postoperative day 3. Serum creatinine was measured preoperatively and postoperatively on day 3 and on day 5. A 24-hour serum creatinine clearance was measured on days 1, 5, and 14. Urine output was recorded hourly during the infusion period.


RESULTS
Ten patients received alprostadil, and 11 patients received placebo. There was a significant increase in GFR and ERPF in both groups on post-operative day 3 as compared with baseline values. There was no difference in GFR and ERPF between the two groups on day 3 (48 +/- 18 and 246 +/- 68 mL/minute in the alprostadil group compared with 53 +/- 17 and 270 +/- 131 mL/minute in the placebo group). Serum creatinine levels increased on day 3 in both groups but returned to baseline by day 5.


CONCLUSIONS
These results indicate that a reversible decrease in GFR is common on hepatic transplant patients during the postoperative period. Administration of a continuous intravenous infusion of alprostadil in the immediate postoperative period had no effect on renal function when compared with placebo.
Manasia
A R
AR
Department of Surgery, Anesthesiology, and Nuclear Medicine, The Mount Siani Medical Center, New York 10029, USA.
Leibowitz
A B
AB
Miller
C M
CM
Silverstein
J H
JH
Schwartz
M
M
Delgiudice
R
R
Vallabhajosula
S
S
Oropello
J M
JM
Benjamin
E
E
D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D017211:Treatment Failure; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D003404:Creatinine; D000527:Alprostadil