Predictors of long-term renal function after conversion to proliferation signal inhibitors in long-term heart transplant recipients

• Published in: The Journal of heart and lung transplantation Vol. 30; no. 5; pp. 552 - 557
• Main Authors: González-Vilchez, Francisco, MD, PhD, Vázquez de Prada, Jose A., MD, PhD, Castrillo, Cristina, MD, Canteli, Angela, MD, Llano, Miguel F., MD, Martín-Durán, Rafael, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2011; Elsevier
• Subjects: Adult; Aged; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological and medical sciences; Calcineurin Inhibitors; Cardiology. Vascular system; Everolimus; Female; Follow-Up Studies; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; heart transplantation; Heart Transplantation - immunology; Humans; Immunosuppressive Agents - pharmacology; Kidney - drug effects; Kidney - physiology; Longitudinal Studies; Male; Medical sciences; Middle Aged; Multivariate Analysis; Predictive Value of Tests; renal function; Retrospective Studies; sirolimus; Sirolimus - analogs & derivatives; Sirolimus - pharmacology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; renal function; everolimus; heart transplantation; sirolimus; Heart; Renal function; Predictor; Transplantation; Proliferation; Homotransplantation; Conversion; Long term; Phlebology; Drug conversion; Signal; Treatment; Surgery; Graft; Inhibitor; Circulatory system; Cardiology; Predictive factor
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2010.11.005

Background The purpose of this study was to evaluate the change in renal function and its determinants after replacement of calcineurin inhibitors with a proliferation signal inhibitor (sirolimus or everolimus) in long-term heart transplant recipients. Methods We studied 49 consecutive patients in whom a switch to a proliferation signal inhibitor was carried out 9 ± 4 years after transplantation. Evolutive glomerular filtration rate was assessed at a mean of 28 months after conversion by the simplified MDRD equation. Results Pre-conversion glomerular filtration rate (40 ± 22 ml/min/1.73 m2 ) remained stable at 1 year after conversion (41 ± 22 ml/min/1.73 m2 ), but decreased significantly by the end of follow-up (35 ± 22 ml/min/1.73 m2 ; p = 0.008 and p = 0.002 vs pre-conversion and 1-year values, respectively). In a multivariate model, including age, time from transplantation to conversion, pre-conversion glomerular filtration rate, presence of diabetes and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy, the rate of decline in renal function was related only to the presence of diabetes ( p = 0.017) and inversely related to the use of ACEI/ARB therapy ( p = 0.003). There were no significant differences with respect to age, time between transplantation and replacement and baseline glomerular filtration rate. Conclusion In long-term heart transplant recipients, late substitution of a calcineurin inhibitor for a proliferation signal inhibitor does not preclude a decrease in renal function in the long-term setting. We identified the presence of diabetes as the main clinical predictor of renal function deterioration. In contrast, we found that the use of ACEI/ARB therapy could exert a protective effect.