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Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients

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Summary

Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 620 ng/kg bw·min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4 : 1.5 ± 0.11 vs. 2.19 ± 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4 : 109 ± 8 vs. 154.7 ± 8.94 mg/dl ; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls. The mean central venous pressure was significantly lower by about 50% (P = 0.02) during the administration of urodilatin in spite of reduced vasodilator medication with nitroglycerin. From this phase IIa study, we may conclude that urodilatin could be an important drug in intensive care treatment. For patients undergoing HTx, this peptide seems to be indicated for the improvement of renal function and cardiovascular status, especially in postoperative therapy using high-dose cyclosporin A treatment.

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Abbreviations

ACE:

angiotensin converting enzyme

ANP:

atrial natriuretic polypeptide

ATG:

antithymocyte globulin

bpm:

beats per minute

bw:

body weight

CDD:

cardiodilatin

CDD/ANP-99-126:

circulating form of vasorelaxant cardiac peptide

CHD:

coronary heart disease

CyA:

cyclosporin A

DCM:

dilated cardiomyopathy

GLM:

general linear model

hANP:

human atrial natriuretic polypeptide

HTx:

heart transplantation

NTG:

nitroglycerine

PC:

plasma creatinine

SU:

serum urea

SAS:

statistical analysing system

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Authors and Affiliations

  1. Deutsches Herzzentrum, Berlin

    M. Hummel, H. Bittner & R. Hetzer

  2. Niedersächsisches Institut für Peptid-Forschung (IPF), Hannover, Germany

    M. Kuhn, A. Bub, D. Kleefeld, P. Marxen & W. G. Forssmann

  3. Zentrum für Biometrie, Medizinische Hochschule Hannover, Hannover, Germany

    B. Schneider

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  1. M. Hummel
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  2. M. Kuhn
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  4. H. Bittner
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  7. B. Schneider
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  8. R. Hetzer
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  9. W. G. Forssmann
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Hummel, M., Kuhn, M., Bub, A. et al. Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients. Clin Investig 70, 674–682 (1992). https://doi.org/10.1007/BF00180284

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