Cystic fibrosis related diabetes before lung transplantation impacts survival but not long-term renal function

Abstract

Introduction Lung transplantation (LT) is the final therapeutic option for cystic fibrosis (CF) patients with end stage lung disease. Lung transplanted CF patients differ from other LT patients because of their younger age, better survival after LT, but also specific associated comorbidities related to their underlying disease, particularly CF related diabetes (CFRD). The objective was to describe the prevalence of CFRD before and after LT; and to analyse survival and renal function after LT according to CFRD status before LT. Methods CF patients treated in the Lyon CF reference centre and transplanted at the Lyon University Hospital (France) between 2004 and 2014 were retrospectively included. Genotype (classified in delF508 homozygous, delF508 heterozygous or other), pancreatic status, age at LT and survival were recorded. The following criteria were recorded three months before LT, between three and six months after LT, and at each year of follow-up until December 2016: glucose tolerance status (CFRD or others), daily insulin dose requirement; renal function, defined by the estimated glomerular filtration rate (GFR, calculated with the Modification of Diet in Renal Disease formula); and daily glucocorticoid (GC) dose. Analysis for repeated measures data was conducted by using linear mixed-effect regression models that included fixed and random effects. Results Sixty-three adult CF patients were transplanted. Thirty-two (53.3%) patients were delF508 homozygous. All were pancreatic insufficient, and 42 (70%) had CFRD before LT. The mean ± SD calculated GFR before LT was 109 ± 47 mL/min/1.73 m2, and did not differ according to CFRD status (P = 0.68). The mean ± SD age at LT was 27.6 ± 8.4 year. The median (IQR) time of follow-up was 5.6 (3.8–8.2) years and 12 (20%) patients died in the follow-up: three patients died in the first three post-operative months, seven patients in the five years following LT and the last two respectively at 6 and 8 years after the LT. The prevalence of CFRD was 68% (41/60) and 54% (20/37) respectively at two and five years after LT. For the 27 patients who had persistent insulin-treated CFRD, insulin requirement decreased with an estimated slope of −2.1 ± 2.9 IU/day per year (P Conclusions CFRD before LT was associated with a poor survival after LT in CF patients, which should conduct to a better management of diabetes control in the peri- and post-operative period after LT. Some patients with pre-LT CFRD get free of diabetes after LT. CFRD is not associated with renal insufficiency after LT. Others factors might participate to renal insufficiency after LT such as perioperative hemodynamic conditions and immunosuppressive drugs.