Assessing treatment outcomes in CLAD: The Hannover-extracorporeal photopheresis model.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treatment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course. METHODS: Retrospective analysis of patients completing ≥3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were compared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation. RESULTS: Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photopheresis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation. CONCLUSIONS: Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treatment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible.

Risk of acute kidney injury after contrast-enhanced computerized tomography: a systematic review and meta-analysis of 21 propensity score-matched cohort studies.

OBJECTIVES: Intravenous application of contrast media is part of a wide spectrum of diagnostic procedures for better imaging quality. Clinical avoidance of contrast-enhanced imaging is an ever-present quandary in patients with impaired kidney function. The objective of this study was to estimate the risk for acute kidney injury (AKI), dialysis and mortality among patients undergoing contrast-enhanced CT compared to propensity score-matched controls (i.e. contrast-unenhanced CT). Selected cohort studies featured high-risk patients with advanced kidney disease and critical illness. METHODS: This review was designed to conform to the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was searched from August 2021 to November 2021 for all-language articles without date restriction. A random-effects model (DerSimonian and Laird method) was used for meta-analysis. RESULTS: Twenty-one articles were included, comprising data of 169,455 patients. The overall risk of AKI was similar in the contrast-enhanced and unenhanced groups (OR: 0.97 [95% CI: 0.85; 1.11], p = 0.64), regardless of baseline renal function and underlying disease. Substantial heterogeneity was detected (I2 = 90%, p ≤ 0.0001). Multivariable logistic regression identified hypertension (p = 0.03) and estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 (p = 0.0001) as factors associated with greater risk of post-contrast AKI. CONCLUSIONS: Based on propensity score-matched pairs obtained from 21 cohort studies, we found no evidence for increased risk for AKI, dialysis or mortality after contrast-enhanced CT among patients with eGFR ≥ 45 mL/min/1.73 m2. In congruence with the emerging evidence in the literature, caution should be exercised in patients with hypertension and eGFR ≤ 30 mL/min/1.73 m2. KEY POINTS: • The application of contrast media for medical imaging is not associated with higher odds for AKI, induction of renal replacement therapy, or mortality. Many comorbidities traditionally associated with greater risk for acute kidney injury do not appear to predispose for renal decline after contrast media exposure. • Underlying hypertension and eGFR less than or equal to 30 mL/min/1.73 m2 seem to predispose for post-contrast acute kidney injury. • Propensity score matching cannot account for unmeasured influences on AKI incidence, which needs to be addressed in the interpretation of results.

Changes in AZGP1 Serum Levels and Correlation With Pulse Wave Velocity After Kidney Transplantation.

Background: Zinc-alpha 2-glycoprotein (AZGP1), a secreted protein with ubiquitous tissue expression, has been controversially linked to the risk of cardiovascular disease. In a cohort of kidney transplant recipients, we measured serum AZGP1 levels after transplantation over a 2 year period and tested for an association with pulse wave velocity as an important parameter indicating future cardiovascular events. Methods: Annual blood sampling and pulse wave velocity measurements were longitudinally performed in 113 kidney transplant recipients. AZGP1 was measured in serum samples using standard ELISA. Association of AZGP1 with pulse wave velocity was longitudinally assessed during follow up of 2 years by mixed longitudinal modeling. Results: AZGP1 serum levels declined significantly after kidney transplantation. This decline was dependent on allograft function as indicated by inverse correlation with eGFR. When corrected for eGFR multivariable analysis revealed an inverse correlation between AZGP1 and pulse wave velocity. This analysis further showed independent associations of older age, higher blood pressure, and higher calcium phosphate product with higher pulse wave velocity. Conclusions: Improved kidney function after transplantation leads to a decline in AZGP1 serum levels. Independent of kidney function and other cardiovascular risk factors lower AZGP1 levels are associated with higher pulse wave velocity in the 2 years after kidney transplantation. These data suggest that AZGP1 might be a potential biomarker for cardiovascular health and a target for improving cardiovascular outcome.

Prospective assessment of subclinical cardiovascular damage and associated factors in liver transplant recipients.

Cardiovascular (CV) disease plays a major role after liver transplantation (LT). This prospective study assessed subclinical CV damage after LT by measuring pulse wave velocity (PWV), intima-media thickness (IMT) and left-ventricular mass index (LVMI) and characterized associated risk factors. We included 112 patients with a median of 1.8 years after LT (q1-q3 0.9-9.2). Fifty-three percent (n = 59) of patients had ≥2 annual assessments (median follow-up 1.6 years, q1-q3 1.1-2.0), with a total of 195 assessments. We found increased PWV (indicating arteriosclerosis) in 16% (n = 17), elevated IMT in 5% (n = 5; indicating atherosclerosis) and increased LVMI in 25% (n = 24; indicating left-ventricular hypertrophy). A linear mixed model analysis using all 195 assessments revealed that higher age and systolic blood pressure (BP) were associated with higher PWV (ß = 0.069, P < 0.001 and ß = 0.022, P = 0.005) and higher IMT (ß = 0.005, P < 0.001 and ß = 0.001, P = 0.029), while higher body mass index was associated with higher IMT (ß = 0.004, P = 0.023). Higher systolic BP (ß = 0.200, P = 0.034), male sex (ß = 8.847, P = 0.031) and lower glomerular filtration rate (ß = -0.288, P < 0.001) were associated with higher LVMI. Our data highlight not only the rate of subclinical CV damage in LT patients, but also the impact of classical CV risk factors (such as BP and body mass index) which outweighed LT-related factors. These modifiable risk factors are suitable targets for interventions to reduce CV morbidity in LT patients.