Elevated fibrinogen to pre-albumin ratio predicts mortality in peritoneal dialysis patients.

BACKGROUND: Fibrinogen to pre-albumin ratio (FPR) is a promising predictor of mortality in various cancers. The aim of this study was to explore the prognostic value of FPR to predict mortality in peritoneal dialysis (PD) patients. METHODS: We retrospectively analyzed 324 incident PD patients form January 2011 to December 2020. Patients were stratified based on the optimal thresholds for FPR at baseline to predict overall and cardiovascular mortality during follow-up. The association of FPR and all-cause and cardiovascular mortality was evaluated by Kaplan-Meier curve and Cox regression analysis. RESULTS: All patients were divided into three groups based on the optimal cutoff value of FPR. Higher FPR levels were strongly correlated with worse overall and cardiovascular mortality in PD patients. Compared with patients in the lowest FPR tertile (<14.3), those in the highest terile (≥18.8) had multivariable-adjusted hazard ratios (95% CI confidence interval) of 3.37 (1.76-6.49) and 2.86 (1.31-6.23) for all-cause and cardiovascular mortality, respectively. Significant differences in overall survival were observed across nearly all subgroups after stratification. CONCLUSIONS: Patients with a high FPR had increased all-cause and cardiovascular mortality. FPR is a potential prognostic indicator in PD patients.

Predictive value of glycemic gap and stress glycemia ratio among critically ill patients with acute kidney injury: a retrospective analysis of the MIMIC-III database.

BACKGROUND AND AIMS: Acute hyperglycemia has been identified as a risk factor for acute kidney injury occurrence and mortality in various diseases. The aim of the current study was to investigate the relationship between stress-induced hyperglycemia and adverse outcomes in critically ill patients with AKI. METHODS: We extracted clinical data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4. Blood glucose and glycosylated hemoglobin during the first 24 h of ICU admission were used to calculate glycemic gap and stress hyperglycemia ratio (SHR). The outcomes included ICU mortality and need for renal replacement therapy. The association of the glycemic gap and SHR with outcomes were determined via logistic regression model and receiver-operating curves. The subgroup analysis of patients with and without diabetes was performed separately. RESULTS: Higher glycemic gap and SHR were observed in patients who had increased need of RRT, higher mortality rates and longer ICU stay. Multivariate analysis demonstrated that higher glycemic gap (OR 1.01, 95%CI 1.00-1.02, P = 0.015), as well as SHR (OR 1.32; 95%CI 1.07-1.64, P = 0.009), were independently associated with ICU mortality after adjusting for potential covariates. In subgroup analysis, the association of glycemic gap and SHR were only significant in the non-diabetic population as for the outcome of ICU mortality (OR 2.25, 95%CI 1.64-3.08, P < 0.001 and OR 1.99; 95%CI 1.46-2.72, P < 0.001, respectively). CONCLUSIONS: The glycemic gap and SHR might serve as a potential prognostic indicator of ICU mortality in critically ill patients with AKI, especially in the non-diabetic population.

Tubular Epithelial Cell HMGB1 Promotes AKI-CKD Transition by Sensitizing Cycling Tubular Cells to Oxidative Stress: A Rationale for Targeting HMGB1 during AKI Recovery.

SIGNIFICANCE STATEMENT: Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from tubular epithelial cells, nor HMGB1 antagonism with small molecules, affects initial ischemic tubular necrosis and immediate GFR loss upon unilateral ischemia/reperfusion injury (IRI). On the contrary, tubular cell-specific HMGB1 deficiency, and even late-onset pharmacological HMGB1 inhibition, increased functional and structural recovery from AKI, indicating that intracellular HMGB1 partially counters the effects of extracellular HMGB1. In vitro studies indicate that intracellular HMGB1 decreases resilience of tubular cells from prolonged ischemic stress, as in unilateral IRI. Intracellular HMGB1 is a potential target to enhance kidney regeneration and to improve long-term prognosis in AKI. BACKGROUND: Late diagnosis is a hurdle for treatment of AKI, but targeting AKI-CKD transition may improve outcomes. High mobility group box-1 (HMGB1) is a nuclear regulator of transcription and a driver of necroinflammation in AKI. We hypothesized that HMGB1 would also modulate AKI-CKD transition in other ways. METHODS: We conducted single-cell transcriptome analysis of human and mouse AKI and mouse in vivo and in vitro studies with tubular cell-specific depletion of Hmgb1 and HMGB1 antagonists. RESULTS: HMGB1 was ubiquitously expressed in kidney cells. Preemptive HMGB1 antagonism with glycyrrhizic acid (Gly) and ethyl pyruvate (EP) did not affect postischemic AKI but attenuated AKI-CKD transition in a model of persistent kidney hypoxia. Consistently, tubular Hmgb1 depletion in Pax8 rtTA, TetO Cre, Hmgb1fl/fl mice did not protect from AKI, but from AKI-CKD transition. In vitro studies confirmed that absence of HMGB1 or HMGB1 inhibition with Gly and EP does not affect ischemic necrosis of growth-arrested differentiated tubular cells but increased the resilience of cycling tubular cells that survived the acute injury to oxidative stress. This effect persisted when neutralizing extracellular HMGB1 with 2G7. Consistently, late-onset HMGB1 blockade with EP started after the peak of ischemic AKI in mice prevented AKI-CKD transition, even when 2G7 blocked extracellular HMGB1. CONCLUSION: Treatment of AKI could become feasible when ( 1 ) focusing on long-term outcomes of AKI; ( 2 ) targeting AKI-CKD transition with drugs initiated after the AKI peak; and ( 3 ) targeting with drugs that block HMGB1 in intracellular and extracellular compartments.

The Impact of Zinc Supplementation on Critically Ill Patients With Acute Kidney Injury: A Propensity Score Matching Analysis.

Background: Zinc is an essential trace element involved in multiple metabolic processes. Acute kidney injury (AKI) is associated with low plasma zinc, but outcomes with zinc supplementation in critically ill patients with AKI remain unknown. Our objective was to investigate the effectiveness of zinc supplementation in this patient population. Methods: Critically ill patients with AKI were identified from the Medical Informative Mart for Intensive Care IV database. Prosperity score matching (PSM) was applied to match patients receiving zinc treatment to those without zinc treatment. The association between zinc sulfate use and in-hospital mortality and 30-day mortality, need for renal replacement therapy (RRT), and length of stay was determined by logistic regression and Cox proportional hazards modeling. Results: A total of 9,811 AKI patients were included in the study. PSM yielded 222 pairs of patients who received zinc treatment and those who did not. Zinc supplementation was associated with reduced in-hospital mortality (HR = 0.48 (95% CI: 0.28, 0.83) P = 0.009) and 30-day mortality (HR = 0.51 (95% CI, 0.30, 0.86) P = 0.012). In the subgroup analysis, zinc use was associated with reduced in-hospital mortality in patients with stage 1 AKI and those with sepsis. Conclusions: Zinc supplementation was associated with improved survival in critically ill patients with AKI. The supplementation was especially effective in those with stage 1 AKI and sepsis. These results need to be verified in randomized controlled trials.

Prognostic Significance of the Albumin to Fibrinogen Ratio in Peritoneal Dialysis Patients.

Background: Albumin to fibrinogen ratio (AFR) is a demonstrated predictor of mortality in various diseases. The aim of this study was to evaluate the prognostic value of AFR to predict mortality in peritoneal dialysis (PD) patients. Methods: We retrospectively analyzed 212 incident PD patients from January 2010 to December 2017 and followed them until December 2019. We used receiver operating curve (ROC) analysis to determine the optimal cut-off point for AFR at baseline to predict overall and cardiovascular mortality during the follow-up period. Kaplan-Meier curve and Cox regression analysis were applied to evaluate the association between AFR and all-cause and cardiovascular mortality. Results: The optimal threshold for AFR to predict mortality was 8.48. A low AFR was strongly correlated with worse all-cause and cardiovascular mortality in PD patients. Multivariate analysis revealed that elevated AFR was an independent marker predicting reduced all-cause and cardiovascular mortality (HR 2.41, 95% CI 1.11-5.22, P = 0.026; and HR 2.18, 95% CI 1.21-3.95, P = 0.010, respectively). Conclusions: Patients with a high AFR had reduced all-cause and cardiovascular mortality. AFR is a potential prognostic biomarker in PD patients.