Abstract End-stage kidney disease (ESKD) demands novel treatments capable of simulating the physiological functions of native kidneys. The bioartificial kidney (BAK), combining a glomerular biomimetic filter and a cell-based bioreactor to restore tubular functions, is a promising therapeutic option that is still under preclinical development. This article reviews the technological evolution of BAK, summarizes the latest progress in membrane materials, cell resources and bioreactor construction, and elaborates on key supporting technologies such as kidney-on-a-chip systems, decellularization-recellularization and device miniaturization. Although considerable achievements have been made, critical hurdles including poor biocompatibility, unstable cell activity, immune isolation defects and insufficient vascularization still hinder its clinical application. Future development depends on interdisciplinary collaboration between precision medicine and smart bioengineering, to ultimately promote the clinical translation of BAK for ESKD treatment.
Objective To assess the association between Life's Essential 8 (LE8) cardiovascular health score and prevalent microvascular complications in Chinese adults with type 2 diabetes mellitus (T2DM) and to explore whether this association differed by sex and menopausal status.Research design and methods We conducted a cross-sectional analysis of 4527 adults with T2DM in the Metabolic Management Center (MMC) registry. LE8 scores were calculated based on the American Heart Association framework and categorized into low, moderate and high tiers using the 25th and 75th percentiles as cut-offs. Prevalent composite microvascular complications were defined as diabetic kidney disease, diabetic retinopathy and/or diabetic peripheral neuropathy. Multivariable logistic regression estimated prevalence ORs and 95% CIs for the associations of LE8 scores with prevalent microvascular complications. Restricted cubic spline (RCS) analyses and interaction testing by sex and menopausal status were also conducted.Results Participants included 2894 men (63.9%), 557 premenopausal women (12.3%) and 1076 postmenopausal women (23.8%). Higher LE8 scores were associated with lower prevalence odds of microvascular complications. Compared with the low LE8 group, the adjusted prevalence OR for the high LE8 group was 0.43 (95% CI 0.36 to 0.52). The inverse association differed by sex and menopausal status (p for interaction=0.027) and appeared strongest in premenopausal women (high LE8 OR: 0.17, 95% CI 0.09 to 0.33). The RCS curves showed broadly similar inverse associations across groups.Conclusions Higher LE8 scores are inversely associated with prevalent microvascular complications in Chinese adults with T2DM. The inverse association appeared strongest in premenopausal women. These findings suggest that sex and menopausal status should be considered when interpreting the observed association.
The significance of endotoxemia during cardiopulmonary bypass remains incompletely understood. This review summarizes decades of research and highlights that clinically relevant endotoxemia affects only a subset of patients, making indiscriminate endotoxin-targeted therapies unlikely to provide meaningful benefit. Future research should therefore focus on identifying high-risk phenotypes, refining endotoxin assessment, and developing personalized therapeutics. Key priorities include standardization of endotoxin measurement, source tracking, gut barrier dysfunction, bypass-related factors, immunological profiling, EndoCAb-guided risk stratification, novel pharmacological approaches, and extracorporeal endotoxin removal. Regarding patient selection for therapeutic intervention, two high-risk subgroups warrant consideration. First, patients with EAA values >0.40 may be considered biologically exposed, while those with EAA values >0.60 represent a subgroup with endotoxin activity approaching levels seen in severe systemic inflammation or sepsis. Importantly, endotoxin activity must always be interpreted in relation to the host's neutralizing capacity. Second, reduced EndoCAb levels independently predict adverse outcomes after cardiac surgery, including prolonged mechanical ventilation, postoperative complications, and extended hospitalization. These patients may be particularly vulnerable to even moderate endotoxin exposure due to impaired endogenous neutralization. Precision medicine strategies targeting these identifiable subgroups represent the most promising path forward.
Introduction: Continuous renal replacement therapy (CRRT) is effective for severe acute kidney injury (AKI); however, predicting successful CRRT discontinuation and long-term outcomes remains challenging. Although urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and kidney volume measured by computed tomography (CT) have been associated with renal prognosis, it remains unclear whether their combination improves predictive accuracy. This study evaluated whether combining urinary NGAL levels with kidney volume measured by CT improves prediction accuracy. Methods: In this retrospective cohort study, urinary NGAL levels and height-adjusted total kidney volume (HtTKV) were assessed for their ability to predict successful CRRT discontinuation and major adverse kidney events at 90 days (MAKE90). Results: Among the 74 patients included, CRRT discontinuation was successful in 55 (74.3%), and MAKE90 occurred in 31 (41.9%). Urinary NGAL (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.76–0.95) was a significant predictor of CRRT discontinuation, whereas HtTKV was not. For long-term outcomes, urinary NGAL (AUC, 0.73 [95% CI, 0.61–0.85]) and HtTKV (AUC, 0.67 [95% CI, 0.54–0.80]) were significantly associated with MAKE90. Adding HtTKV to urinary NGAL significantly improved the prediction of MAKE90, as demonstrated by reclassification analyses (net reclassification improvement and integrated discrimination improvement). Conclusions: Adding HtTKV significantly improved the prediction of long-term MAKE90 based on NGAL levels, but not that of short-term CRRT discontinuation. These findings in this proof-of-concept study suggest that structural kidney assessment by CT volumetry may complement urinary NGAL for long-term risk stratification in patients with severe AKI requiring CRRT.
