Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Kidney Transplantation in Patients With Chronic Kidney Disease After a Previous Lung Transplantation.

BACKGROUND: The development of chronic kidney disease is a common complication after a lung transplantation, especially since the introduction of immunosuppressive treatments based on calcineurin inhibitors. Many of these patients reach end-stage renal disease and even need renal replacement therapy. Among the different options of renal replacement therapy, we consider kidney transplantation as a feasible option for these patients. METHODS: A single center, observational retrospective study including 8 lung transplanted patients who have received a kidney transplant in the period between 2013 and 2017 with at least 1 year of follow-up was used. RESULTS: Seven patients maintained an adequate function of the graft 1 year after kidney transplantation, and 1 patient died because of a pulmonary condition in spite of a previous kidney transplant. Two patients presented delayed graft function in the first days after surgery. CONCLUSIONS: The kidney transplantation is a technique of renal replacement therapy that should be considered in patients with previous lung transplantation. Experienced centers in double sequential lung and kidney transplantation should be established to assess and treat these types of patients.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Midterm Results of Renal Transplantation From Controlled Cardiac Death Donors Are Similar to Those From Brain Death Donors.

BACKGROUND: The systematic use of grafts from controlled donors after cardiac death (cDCD) started in our country in 2012 and expanded with the strategic support of National Transplant Organization. We present our experience in kidney transplantation with organs from cDCD donors with a mean follow-up of 3 years. METHODS: Observational prospective study of all transplants performed in our center in 2012-2013 followed to 2016. The immunosuppression protocols were triple therapy for low-risk recipients from a standard brain death donor (DBD), adding basiliximab or thymoglobulin induction for extended-criteria donor or high-risk recipient, respectively, and thymoglobulin induction plus triple therapy for all cDCD recipients. RESULTS: A total of 42 donors were included (84 grafts in total, but 1 discarded due to multiple cysts); 25 DBD and 17 cDCD without differences in age or sex. The graft use rate was 98.9% for cDCD; 55 grafts were implanted in our hospital (26 DBD and 29 cDCD), and the remaining 28 grafts were transferred to other centers. There were no differences in primary failure (3.4% cDCD vs 7.4% DBD), but the cDCD organs had a higher incidence of delayed graft function (51.7% vs 25.9%). Despite that, graft and patient survivals, as well as glomerular filtration rate (66.3 vs 59.6 mL/min) were similar in both groups. Only 1 patient died at home with a functioning graft in the cDCD group. CONCLUSIONS: Despite a higher rate of delayed graft function with cDCD, the midterm outcomes are at least similar to those with DBD. The cDCD programs should be promoted to increase the chances of a transplant in our patients.

Kidney transplantation with organs from donors after circulatory death type 3: a prospective multicentric Spanish study (GEODAS 3).

To increase the number of kidney donors, new strategies are needed such as living donor programs, expanded criteria donors, or donors after circulatory death (DCD) kidney transplantation programs. The GEODAS group has started an observational, prospective, multicenter clinical study, collecting data from all DCD type-3 kidney transplantations performed in seven Spanish hospitals from January 2012 to January 2014. The preliminary results have shown a delayed graft function of 40.4% and graft survival of 93.7% with a nadir creatinine of 1.3 mg/dL. From all 33 potential donors included in the study, 32 were effective and 63 kidney grafts were transplanted with a utilization rate of 98.5%. Creatinine evolution (median [range]) was in the first month: 2.1 [0.6-5.6]; third month: 1.6 [0.8, 4.2]; first year: 1.6 [0.9-2.2]. These results are similar to kidney transplantation from donors after brain death as shown in the literature, especially in the graft and recipient survival rates. In addition, the controlled programs are easier and less expensive than uncontrolled DCD programs with a higher rate of graft use.