Fat mass: a novel digital biomarker for remote monitoring that may indicate risk for malnutrition and new complications in decompensated cirrhosis.

BACKGROUND: Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care. METHODS: A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing's bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed. RESULTS: 73.3% (11/15) patients were male with a median age of 63 (52-68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031). CONCLUSIONS: This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.

Divergent effects of AKI to CKD models on inflammation and fibrosis.

Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low-dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis. We demonstrate both models instigate renal dysfunction, inflammatory cytokine responses, and fibrosis. However, the models exhibit differences in urinary excretory function, inflammatory cell infiltration, and degree of fibrotic response. UIRI without CLN demonstrated worsening perfusion and function, measured with 99mTc-mercaptoacetyltriglycine-3 imaging, and physiologic compensation in the contralateral kidney. Furthermore, UIRI without CLN elicited a robust inflammatory response that was characterized by a prolonged polymorphonuclear cell and natural killer cell infiltrate and an early expansion of kidney resident macrophages, followed by T-cell infiltration. Symmetrical diminished function occurred in RLDC kidneys and progressively worsened until day 17 of the study. Surprisingly, RLDC mice demonstrated a decrease in inflammatory cell numbers relative to controls. However, RLDC kidneys expressed increased levels of kidney injury molecule-1 (KIM-1), high mobility group box-1 ( HMGB1), and colony stimulating factor-1 ( CSF-1), which likely recruits inflammatory cells in response to injury. These data emphasize how the divergent etiologies of AKI to CKD models affect the kidney microenvironment and outcomes. This study provides support for subtyping AKI by etiology in human studies, aiding in the elucidation of injury-specific pathophysiologic mechanisms of the AKI to CKD transition.