Circulating Adrenomedullin Is Increased After Renal Transplantation B. Geny, S. Doutreleau, B. Elero, F. Bronner, C. Brandt, E. Epailly, B. Mettauer, M. Zupan, N. Chakfe ´, and F. Piquard A DRENOMEDULLIN (ADM), a newly discovered potent vasorelaxing and natriuretic peptide, is in- creased during hypertension, heart failure and heart trans- plantation. 1–5 Like other vasoactive substances such as cardiac natriuretic peptides or endothelin, ADM might also be elevated in renal transplant patients (Rtx). 6–8 We, therefore, investigated ADM plasma levels and its eventual relationships with systemic blood pressure, plasma creati- nine and parameters of cardiac diastolic function after renal transplantation. PATIENTS AND METHODS Ten healthy subjects, 15 hypertensive patients and 10 Rtx 69  14 months after surgery-, participated in this study. Circulating ADM was determined at rest as previously described 8 and cardiac func- tion was obtained with doppler echocardiography (Advanced Tech- nology Laboratories (Bothrell, Wash). RESULTS Mean blood pressure is increased in hypertensive patients (101  2 mm Hg), but not significantly in Rtx. Creatinine is increased in Rtx (171  32 umol/L). ADM is increased in Rtx as compared to normal subjects (69.1  10.6 pmol/L, P  .001), such increase being similar to that observed in hypertensive patients (70.2  5.2 pmol/L). Althouh no correlation is found between ADM and creatinine, LV mass index, or blood pressure, a negative correlation is observed in Rtx between ADM and the isovolumetric relaxation time (IVRT) (r .66; P  .04) and their ADM and mitral A vave maximal velocity tend to correlate positively (r  .61; P  .06), Fig 1. DISCUSSION Confirming that circulating ADM is increased after renal transplantation, 8 this study demonstrates for the first time that cardiac diastolic dysfunction might stimulate ADM release in Rtx. In agreement with previous data in heart failure or transplanted patients, no relationship was ob- served between ADM and plasma creatinine, supporting that the slight degree of renal impairment observed in Rtx might not account importantly for their ADM in- crease. 3,8 –10 Similarly, although increased ADM has been proposed to be partly related to cardiac hypertrophy in patients with hypertension, 11 we failed to find any relation- ship between raised ADM and systemic blood pressure or left ventricular mass after renal transplantation. Although not statistically significant, the increased blood pressure observed in Rtx resulted nevertheless likely in a moderate increase in IVRT and mitral A vave maximal velocity. And thus, despite the fact that correlation do not imply causa- tion and that the number of Rtx studied is relatively small, the correlations observed between increased ADM and IVRT or mitral A vawe velocity (inverse and positive, respectively), support that cardiac diastolic dysfunction, particularly impaired passive filling of the left ventricle, might participate in ADM increase after renal transplanta- tion. 12 Since ADM inhibits cardiomyocytes hypertrophy 13 and oppose vasoconstrictive and antinatriuretic peptides, it suggests that increased ADM might be protective against hypertension-induced deleterious effets in Rtx and supports that therapeutic strategies aiming to increase circulating ADM might ameliorate Rtx’s cardiac and renal functions, enhancing thus both their duration and quality of life. 14 From the Physiology, Cardiology, and Transplantation Depart- ments, Strasbourg, France. Address reprint requests to Dr Bernard Geny, Institut de Physiologie, Faculte ´ de Me ´ decine, 67085 Strasbourg Cedex, France. E-mail: Bernard.Geny@physio-ulp.u-strasbg.fr. Fig 1. Relationships between plasma ADM and mitral A wave maximal velocity (r  .61, P  .06). 0041-1345/01/$–see front matter © 2001 by Elsevier Science Inc. PII S0041-1345(01)02463-0 655 Avenue of the Americas, New York, NY 10010 3396 Transplantation Proceedings, 33, 3396–3397 (2001)