Prognostic importance of renal function 1 year after heart transplantation for all-cause and cardiac mortality and development of allograft vasculopathy.

BACKGROUND: Impaired renal function is associated with increased mortality among heart failure patients. Although a significant proportion of heart transplant (HTx) recipients have reduced renal function at 1 year post-HTx, no previous study has evaluated the associated risk for both all-cause and cardiac mortality. Hence, we assessed the relationship between glomerular filtration rate (GFR) at 1 year post-HTx and all-cause and cardiac mortality and development of cardiac allograft vasculopathy (CAV). METHODS: We evaluated 381 patients with a minimum survival of 1 year post-HTx and the Modification of Diet in Renal Disease Study formula was used to calculate estimated GFR. Mortality and angiographic CAV were defined as separate endpoints, and median follow-up was 7.4 and 4.0 years, respectively. RESULTS: During the follow-up period, 122 patients died and 154 patients developed CAV. Reduced GFR pre-HTx was not a risk factor for either endpoint. Overall, 193 (51%) patients had GFR <60 ml/min/1.73 m at one year post-HTx and this was an independent predictor of all-cause mortality with an adjusted hazard ratio of 1.7 (P=0.01) for a GFR between 30-60 and 3.2 (P=0.006) for GFR <30 ml/min/1.73 m. GFR <60 ml/min/1.73 m at 1 year post-HTx was also associated with a higher risk of cardiac mortality (HR=1.9; P=0.04) but did not predict the development of CAV. CONCLUSIONS: Renal impairment is evident in a majority of HTx recipients at 1 year post-HTx. It is an important risk factor for both all-cause and cardiac mortality but does not predict the development of angiographic CAV.

Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation.

BACKGROUND: Calcineurin inhibitor (CNI)-induced nephrotoxicity is a feared adverse effect after heart transplantation (HTx). In patients with advanced renal failure we performed an overnight conversion from cyclosporine (CsA) to everolimus within the first year after HTx and compared changes in renal function to a similar switch performed in a group of long-term HTx survivors with 24-month follow up. METHODS: Sixteen HTx recipients (Group 1), including 5 patients undergoing dialysis, were switched overnight from CsA to everolimus at 5.5 (range 1.3 to 8.5) months post-operatively, whereas 15 patients completed 24 months of follow-up. Fifteen long-term survivors (Group 2) were recruited at 96 (58 to 148) months post-HTx. Due to 3 withdrawals and 2 deaths, 10 of these 15 patients remained available for follow-up assessment. RESULTS: In Group 1 patients, creatinine level improved from 211 (186 to 263) to 112 (98 to 140) mumol/liter and estimated glomerular filtration rate (eGFR) from 29 (20 to 35) to 62 (43 to 69) ml/min/1.73 m(2) (p < 0.001). In Group 2, creatinine decreased from 227 (188 to 255) to 193 (150 to 250) micromol/liter (p = 0.299), and eGFR increased from 26 (21 to 31) to 28 (22 to 35) ml/min/1.73 m(2) (p = 0.225). Four cellular rejections were treated successfully in Group 1. All together, 24 adverse events occurred. CONCLUSIONS: These preliminary data are the first to suggest that the improvement in renal function after switching to CNI-free everolimus treatment has the greatest potential within the first year post-HTx. While we await randomized, controlled trials, it appears that conversion can be performed with acceptable safety in selected patients.