The impact of long-term exposure to tacrolimus on chronic kidney disease after lung transplantation: A retrospective analysis from a single transplantation center.

BACKGROUND: Chronic kidney disease (CKD) is a progressive and irreversible complication in lung transplant patients who have received long-term treatment with tacrolimus. This study aimed to verify long-term tacrolimus exposure values in CKD progression. METHODS: We retrospectively analyzed the clinical data of adult lung transplant recipients performed at our center between 2012 and October 2015. Patients who completed the 5-year follow-up period were enrolled in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Eighty patients were analyzed. Compared with baseline (109 ± 38.1 mL/min/1.73 m2), the average eGFR values of our patients gradually decreased during the fifth-year post transplantation (46.5%, 58.3 ± 28.3 mL/min/1.73 m2), and the decline in eGFR values was particularly pronounced in the first year (31.2%, 74.6 ± 28.91 mL/min/1.73 m2). Moreover, 10 (12.7%), 21 (26.9%), 24 (31.2%), 28 (41.2%), and 48 (60%) patients had eGFR <60 mL/min/1.73 m2 at 3, 6, 1, 3, and 5 years after lung transplantation (LT), respectively. A significant negative correlation was found between tacrolimus dose and eGFR 6 months after LT (P = 0.0414). We found no correlation between the serum tacrolimus concentration and CKD progression. CONCLUSION: eGFR constantly decreased and the incidence of CKD increased during the 5-year follow-up period after LT. The tacrolimus dose had a significant negative correlation with eGFR at 6 months after LT. Meanwhile, whole-blood tacrolimus trough concentrations were not correlated with eGFR decline. When possible, lower dosing within 1 year after LT can reduce potential nephrotoxic side effects.

A Retrospective Study of Lung Transplantation in Patients With Lymphangioleiomyomatosis: Challenges and Outcomes.

Background: Lymphangioleiomyomatosis (LAM) is a rare systemic disease that generally leads to a progressive decline in pulmonary function. Experience, especially from the Asian population, including combined drug therapy before and after lung transplantation (LT) in LAM, is still limited. This study aimed to summarize the clinical data from patients with pulmonary LAM who underwent LT at centers in China. Methods: A retrospective review of all patients with LAM undergoing LT at the two largest centers in China between 2010 and 2018 was conducted. Pre- and posttransplant data were assessed and analyzed. Results: Overall, 25 patients with LAM underwent bilateral LT. The mean age was 35.0 ± 8.6 years at diagnosis and 36.8 ± 9.3 years at the time of transplant. Before LT, only six patients could complete pulmonary function test; the reachable mean forced expiratory volume in one second (FEV1) before LT was 15.9 ± 6.9%. Twenty-one patients (84%) had a recurrent pneumothorax, four (16.0%) of which required pleurodesis. Eight patients (32%) were treated with sirolimus pretransplant for 3.9 years (1-9 years). The average intra-surgery bleeding volume was 1,280 ± 730 ml in need of a transfusion of 1,316 ± 874 ml due to moderate-to-severe adhesion and pretransplant pleurodesis. The causes of death of four patients (16%) included primary graft dysfunction, bronchial dehiscence with long-term use of sirolimus, and uncontrollable infections. The median follow-up time from LT was 41.1 ± 25.0 months. Conclusions: LT for LAM patients from the Asian population has been reinforced from the data that we presented. Peri-transplantation use of sirolimus and LAM-related complications should be further defined and under constant surveillance.

Discovery and validation of PZP as a novel serum biomarker for screening lung adenocarcinoma in type 2 diabetes mellitus patients.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies. This study aimed to identify specific biomarkers that can detect lung adenocarcinoma (LAC) in T2DM patients for the early diagnosis of LAC. METHODS: The clinical information of hospitalized T2DM patients diagnosed with various cancers was collected by reviewing medical records in Wuxi People's Hospital Affiliated to Nanjing Medical University from January 1, 2015, to June 30, 2020. To discover diagnostic biomarkers for early-stage LAC in the T2DM population, 20 samples obtained from 5 healthy controls, 5 T2DM patients, 5 LAC patients and 5 T2DM patients with LAC (T2DM + LAC) were subjected to sequential windowed acquisition of all theoretical fragment ion mass spectrum (SWATH-MS) analysis to identify specific differentially-expressed proteins (DEPs) for LAC in patients with T2DM. Then, these results were validated by parallel reaction monitoring MS (PRM-MS) and ELISA analyses. RESULTS: Lung cancer was the most common malignant tumor in patients with T2DM, and LAC accounted for the majority of cases. Using SWATH-MS analysis, we found 13 proteins to be unique in T2DM patients with early LAC. Two serum proteins were further validated by PRM-MS analysis, namely, pregnancy-zone protein (PZP) and insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, the diagnostic values of these proteins were validated by ELISA, and PZP was validated as a novel serum biomarker for screening LAC in T2DM patients. CONCLUSIONS: Our findings indicated that PZP could be used as a novel serum biomarker for the identification of LAC in T2DM patients, which will enhance auxiliary diagnosis and assist in the selection of surgical treatment at an early stage.