Impact of Renal Function and Cardiovascular Risk Factors

Introduction

Posttransplant renal dysfunction and cardiovascular risk factors can be a consequence of either direct or indirect adverse effects of current immunosuppressive regimes. Therefore, different safety profiles of immunosuppressive agents should be taken into account when evaluating their potential impact on long-term survival after heart transplantation. We focus on safety profiles of cyclosporine A (CsA), tacrolimus (Tac), mycophenolate mofetil (MMF) and rapamycin (Rapa) especially in terms of nephrotoxicity, glucose changes, hypertension and hyperlipidemia.

References

• 1 Esposito C, Semeraro L, Bellotti N, Fasoli G, Fornoni A, Rampino T, Klersy C, Campana C, Gavazzi A, Viganò M, Dal Canton A. Risk factors for chronic renal dysfunction in cardiac allograft recipients.  Nephron. 2000;  84 21-28
• 2 van Gelder T, Balk A H, Zietse R, Hesse C, Mochtar B, Weimer W. Survival of heart transplant recipients with cyclosporine-induced renal insufficiency.  Transplant Proc. 1998;  30 1122-1123
• 3 Meiser B M, Uberfuhr P, Fuchs A, Schmidt D, Pfeiffer M, Paulus D, Schulze C, Wildhirt S, Scheidt W V, Angermann C, Klauss V, Martin S, Reichenspurner H, Kreuzer E, Reichart B. Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection.  J Heart Lung Transplant. 1998;  17 782-788
• 4 Taylor D O, Barr M L, Radovancevic B, Renlund D G, Mentzer Jr R M, Smart F W, Tolman D E, Frazier O H, Young J B, Van Veldhuisen P. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus.  J Heart Lung Transplant. 1999;  18 336-345
• 5 Groetzner J, Meiser B M, Schirmer J, Koglin J, vScheidt W, Klauss V, Cremer P, Reichenspurner H, Reichart B. Tacrolimus or cyclosporine for immunosuppression after cardiac transplantation: which treatment reveals more side effects during long-term follow-up?.  Transplant Proc. 2001;  33 1461-1464
• 6 Klein I H, Abrahams A, van Ede T, Hené R J, Koomans H A, Ligtenberg G. Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects.  Transplantation. 2002;  73 732-736
• 7 Angermann C E, Störk S, Costard-Jäckle A, Dengler T J, Siebert U, Tenderich G, Rahmel A, Schwarz E R, Nägele H, Wagner F M, Haaff B, Pethig K. Reduction of cyclosporine after introduction of mycophenolate mofetil improves chronic renal dysfunction in heart transplant recipients–the IMPROVED multi-centre study.  Eur Heart J. 2004;  25 1626-1634
• 8 Eisen H J, Tuzcu E M, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler H A, Starling R C, Sørensen K, Hummel M, Lind J M, Abeywickrama K H, Bernhardt P. RAD B253 Study Group . Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.  N Engl J Med. 2003;  349 847-858
• 9 Meiser B, Reichart B, Adamidis I, Überfuhr P, Kaczmarek I. First experience with de novo calcineurin-inhibitor-free immunosuppression following cardiac transplantation.  Am J Transplant. 2005;  5 827-831
• 10 Pirsch J D, Miller J, Deierhoi M H, Vincenti F, Filo R S. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group.  Transplantation. 1997;  63 977-983
• 11 Woodward R S, Schnitzler M A, Baty J, Lowell J A, Lopez-Rocafort L, Haider S, Woodworth T G, Brennan D C. Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients.  Am J Transplant. 2003;  3 590-598
• 12 Meiser B, Kaczmarek I, Mueller M, Groetzner J, Weis M, Knez A, Stempfle H U, Klauss V, Schmoeckel M, Reichart B, Ueberfuhr P. Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious.  J Heart Lung Transplant. 2007;  26 598-603
• 13 Baan C C, van Riemsdijk-van Overbeeke I C, Balk A H, Vantrimpont P M, Mol W M, Knoop C J, Niesters H G, Maat L P, Weimar W. Conversion from cyclosporin A to tacrolimus is safe and decreases blood pressure, cholesterol levels and TGF-beta 1 type I receptor expression.  Clin Transplant. 2001;  15 276-283
• 14 Akhlaghi F, Jackson C H, Parameshwar J, Sharples L D, Trull A K. Risk factors for the development and progression of dyslipidemia after heart transplantation.  Transplantation. 2002;  73 1258-1264
• 15 Wenke K, Meiser B, Thiery J, Nagel D, von Scheidt W, Krobot K, Steinbeck G, Seidel D, Reichart B. Simvastatin initiated early after heart transplantation: 8-year prospective experience.  Circulation. 2003;  107 93-97
• 16 Kobashigawa J A, Starling R C, Mehra M R, Kormos R L, Bhat G, Barr M L, Sigouin C S, Kolesar J, Fitzsimmons W. Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.  J Heart Lung Transplant. 2006;  25 1063-1069