Invasive fungal diseases in kidney transplant recipients: Risk factors for mortality

Background: Invasive fungal disease (IFD) is common in solid organ transplant (SOT) recipients and contributes to high morbidity and mortality. Although kidney transplantation (KT) is a commonly performed SOT, data on the risk factors for IFD-related mortality are limited. Methods: A 1:2 retrospective case-control study was performed in an experienced single center in the Republic of Korea. We reviewed the electronic medical records of patients with IFD after KT between February 1995 and March 2015. Results: Of 1963 kidney transplant recipients, 48 (2.5%) were diagnosed with IFD. The median interval from KT to IFD diagnosis was 172 days. Invasive aspergillosis (IA) was the most common, followed by invasive candidiasis (IC). Diabetes mellitus (DM) (odds ratio (OR) 3.72, 95% confidence interval (CI) 1.34–10.31, p = 0.011) and acute rejection (OR 3.41, 95% CI 1.41–8.21, p = 0.006) were associated with IFD development. In the subgroup analyses, concomitant bacterial infection was associated with IC development (OR 20.10, 95% CI 3.60–112.08, p = 0.001), and delayed graft function was associated with IA occurrence (OR 10.60, 95% CI 1.05–106.84, p = 0.045). The 12-week mortality rate in all patients was 50.0%. Mortality rates were significantly higher in older patients (adjusted hazard ratio (aHR) 1.06, 95% CI 1.02–1.11, p = 0.004), or those with DM (aHR 2.61, 95% CI 1.02–6.68, p = 0.044), deceased donor transplantation (aHR 2.68, 95% CI 1.03–6.95, p = 0.043), lymphocyte-depleting antibody usage (aHR 0.26, 95% CI 0.08–0.80, p = 0.019), acute rejection (aHR 0.38, 95% CI 0.15–0.97, p = 0.044), and concomitant bacterial infection (aHR 8.76, 95% CI 1.62–47.51, p = 0.012). Conclusions: A total of 50% of IFD cases occurred six months or later after transplantation. The IFD-related mortality rate was high in kidney transplant recipients despite the low incidence. DM and acute rejection were associated with high mortality, as well as IFD development. As old age, deceased donor transplantation, lymphocyte-depleting antibody usage, and concomitant bacterial infection are risk factors for IFD-related mortality, efforts for its early diagnosis and appropriate treatment are required.