Mechanistic differences between phenotypes of chronic lung allograft dysfunction after lung transplantation

Distinct phenotypes of chronic lung allograft dysfunction (CLAD) after lung transplantation are emerging with lymphocytic bronchiolitis (LB)/azithromycin reversible allograft dysfunction (ARAD), classical or fibrotic bronchiolitis obliterans syndrome (BOS), and restrictive allograft syndrome (RAS) proposed as separate entities. We have additionally identified lung transplant recipients with prior LB, demonstrating persistent airway neutrophilia (PAN) despite azithromycin treatment. The aim of this study was to evaluate differences in the airway microenvironment in different phenotypes of CLAD. Bronchoalveolar lavage (BAL) from recipients identified as stable (control), LB/ARAD, PAN, BOS, and RAS were evaluated for differential cell counts and concentrations of IL‐1α, IL‐1β, IL‐6, IL‐8, and TNF‐α. Primary human bronchial epithelial cells were exposed to BAL supernatants from different phenotypes and their viability measured. BOS and RAS showed increased BAL neutrophilia but no change in cytokine concentrations compared with prediagnosis. In both LB/ARAD and PAN, significant increases in IL‐1α, IL‐1β, and IL‐8 were present. BAL IL‐6 and TNF‐α concentrations were increased in PAN and only this phenotype demonstrated decreased epithelial cell viability after exposure to BAL fluid. This study demonstrates clear differences in the airway microenvironment between different CLAD phenotypes. Systematic phenotyping of CLAD may help the development of more personalized approaches to treatment.     

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation

BACKGROUND: This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. METHODS: The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. CONCLUSIONS: The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.     

Noninvasive methods for detection of chronic lung allograft dysfunction in lung transplantation

Lung transplantation (LTx) is the only therapeutic option for end-stage lung diseases. Chronic lung allograft dysfunction (CLAD), which manifests as airflow restriction and/or obstruction, is the primary factor limiting the long-term survival of patients after surgery. According to histopathological and radiographic findings, CLAD comprises two phenotypes, bronchiolitis obliterans syndrome and restrictive allograft syndrome. Half of all lung recipients will develop CLAD in 5 years, and this rate may increase up to 75% 10 years after surgery owing to the paucity in accurate and effective early detection and treatment methods. Recently, many studies have presented noninvasive methods for detecting CLAD and improving diagnosis and intervention. However, the significance of accurately detecting CLAD remains controversial. We reviewed published studies that have presented noninvasive methods for detecting CLAD to highlight the current knowledge on clinical symptoms, spirometry, imaging examinations, and other methods to detect the disease.     

肾移植术后少尿或无尿的诊治体会

报告尸体肾移植术后发生少尿或无尿患者30例,其中有2例无尿时间长达8～12周。均采取严密观察肾脏血供、常规透析、仔细防治排斥反应等并发症的“积极等待”的方法予以治疗,大部分患者移植肾功能均恢复正常;2例长时间无尿的患者亦恢复了正常肾功能,取得了较好的效果。认为彩色多普勒超声对诊断移植肾少尿或无尿有较大帮助,采用“积极等待”的方法治疗肾移植术后的少尿或无尿可取得较好效果。     

Acute allograft rejection after lung transplantation: diagnosis and therapy

Acute rejection remains a significant problem after lung transplantation. While it generally is a treatable condition, significant resources and therapies are directed toward its prevention and resolution. Its larger significance undoubtedly rests in its contribution to the pathogenesis of BOS. Significant questions regarding the origins of AR, the role of LBB, alternative histologic appearances of acute allograft injury, and optimal therapy remain. Controversy regarding the utility of surveillance bronchoscopy and preemptive treatment of occult AR persists because of lack of conclusive evidence. Future investigations might resolve these matters and provide more efficacious and less toxic therapies that will hopefully reduce the impact of chronic rejection and improve long-term outcomes.     

Chronic renal dysfunction late after liver transplantation

With the increasing success of liver transplantation, more patients are developing late complications such as renal dysfunction. The goal of the current study was to assess the prevalence of renal dysfunction years after liver transplantation and to identify patients at risk for the development of this complication. Of the 527 liver transplantations performed at our institution between April 1990 and October 1998, 353 had pretransplantation and posttransplantation glomerular filtration rate (GFR) determinations by iothalamate clearance. From this entire group, 198 patients had actual 4-year follow-up and 52 had actual 6-year follow-up. In addition, 191 of these patients had intensive follow-up with GFR measurements pretransplantation and at 1 and 3 years posttransplantation (complete follow-up group). All patients received either tacrolimus- or cyclosporine-based immunosuppression. The overall mean GFR levels in both of these groups was acceptable and was not different in cyclosporine- versus tacrolimus-based immunosuppressive regimens. Renal dysfunction was progressive, with 27.5% of patients in the intensive group having a GFR < 40 mL/min/body surface area 5 years after transplantation. GFR pretransplantation did not correlate well with late renal function; however, GFR at 1 year identified patients with subsequent renal dysfunction. The cumulative incidence of renal failure for the entire group was 6.25% at 7 years and 10% at 10 years. Renal dysfunction is a major late complication after liver transplantation. The GFR at 1 year correlates best with late renal function. Patients with a low GFR at 1 year (< 40 mL/min/BSA) are a high-risk group that might benefit from early therapeutic interventions aimed at preventing subsequent renal failure. (Liver Transpl 2002;8:916-921.)     

Early onset proteinuria after renal transplantation: a marker for allograft dysfunction

The objective of this study was to determine whether early proteinuria after renal transplantation affected long-term allograft survival. The 130 patients included 105 men and 25 women of overall mean age, 29.6 +/- 9.6 years. There were 105 living related and, 25 cadaveric donor transplants. Proteinuria was defined as a level in of more than 300 mg/d. Donor and recipient age at transplantation, duration of pretransplant dialysis, donor type (living related or cadaveric), the presence of delayed graft function or acute rejection, panel-reactive antibodies, the number of human leukocyte antigen mismatches, and the systolic blood pressure level were retrospectively recorded for the study subjects. Cox regression analysis was used to determine the effects of proteinuria on allograft survival. Patients with proteinuria demonstrated significantly lower graft survival rates than did those without proteinuria (54.17% vs 82.62%, respectively; P<.002). Proteinuria at the third month after transplantation (P<.004, odds ratio [OR]=3.26, confidence interval [CI]=1.46 to 7.29), donor age (P<.001, OR=1.06, CI=1.02 to 109), and panel-reactive antibodies (P<.041, OR=1.06, CI=1.00 to 1.12) were significantly associated with decreased allograft survival. Early proteinuria after renal transplantation was indicative of a high risk for allograft dysfunction. A reduction of proteinuria may be associated with improved graft survival.