The relationship between red cell distribution width, serum calcium ratio, and in-hospital mortality among patients with acute respiratory failure: A retrospective cohort study of the MIMIC-IV database.

To investigate the impact of RDW/CA (the ratio of red cell distribution width to calcium) on in-hospital mortality in patients with acute respiratory failure (ARF). This retrospective cohort study analyzed the data of 6981 ARF patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database 2.0. Critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. The primary outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether the RDW/CA ratio independently correlated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves of the RDW/CA. Subgroup analyses were performed to measure the mortality across various subgroups. After adjusting for potential covariates, we found that a higher RDW/CA was associated with an increased risk of in-hospital mortality (HR = 1.17, 95% CI: 1.01-1.35, P = .0365) in ARF patients. A nonlinear relationship was observed between RDW/CA and in-hospital mortality, with an inflection point of 1.97. When RDW/CA ≥ 1.97 was positively correlated with in-hospital mortality in patients with ARF (HR = 1.554, 95% CI: 1.183-2.042, P = .0015). The Kaplan-Meier curve indicated the higher survival rates for RDW/CA < 1.97 and the lower for RDW/CA ≥ 1.97 after adjustment for age, gender, body mass index, and ethnicity. RDW/CA is an independent predictor of in-hospital mortality in patients with ARF. Furthermore, a nonlinear relationship was observed between RDW/CA and in-hospital mortality in patients with ARF.

Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.

BACKGROUND: Trials have demonstrated lower rates of acute kidney injury in critically ill patients receiving magnesium supplementation, but they have yielded conflicting results regarding mortality. METHODS: This is a retrospective cohort study based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with sepsis were included in the analysis. The exposure was magnesium sulfate use during ICU stay. The primary outcome was 28-day all-cause mortality. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. RESULTS: The pre-matched and propensity score-matched cohorts included 10 999 and 6052 patients, respectively. In the PSM analysis, 28-day all-cause mortality rate was 20.2% (611/3026) in the magnesium sulfate use group and 25.0% (757/3026) in the no use group. Magnesium sulfate use was associated with lower 28-day all-cause mortality (hazard ratio [HR], 0.70; 95% CI, 0.61-0.79; P<0.001). Lower mortality was observed regardless of baseline serum magnesium status: for hypomagnesaemia, HR, 0.64; 95% confidence interval (CI), 0.45-0.93; P=0.020; for normomagnesaemia, HR, 0.70; 95% CI, 0.61-0.80; P<0.001. Magnesium sulfate use was also associated with lower ICU mortality (odds ratio [OR], 0.52; 95% CI, 0.42-0.64; P<0.001), lower in-hospital mortality (OR, 0.65; 95% CI, 0.55-0.77; P<0.001), and renal replacement therapy (OR, 0.67; 95% CI, 0.52-0.87; P=0.002). A sensitivity analysis using the entire cohort also demonstrated lower 28-day all-cause mortality (HR, 0.62; 95% CI, 0.56-0.69; P<0.001). CONCLUSIONS: Magnesium sulfate use was associated with lower mortality in critically ill patients with sepsis. Prospective studies are needed to verify this finding.

RDW-to-ALB Ratio Is an Independent Predictor for 30-Day All-Cause Mortality in Patients with Acute Ischemic Stroke: A Retrospective Analysis from the MIMIC-IV Database.

Purpose: Previous studies have shown that the peripheral red blood cell distribution width (RDW) and human serum albumin (ALB) were both predictors of the risk and mortality of cerebrovascular diseases, and the ratio of RDW to ALB (RAR) was a combined new index that can predict the prognosis of the cardiovascular and respiration systemic diseases, but its role in cerebrovascular diseases had not been effectively evaluated. This study is aimed at exploring whether RAR can effectively predict the 30-day all-cause mortality of acute ischemic stroke (AIS) patients. Methods: This retrospective cohort study was conducted on AIS patients (age > 18 years) in the intensive care database MIMIC-IV. The RAR was measured based on the red blood cell distribution width and albumin. The main result was 30-day all-cause mortality, and the secondary results were ICU mortality and hospital mortality. Obtain the odds ratio (OR) estimate from the logistic regression model of log-transformed RAR values and mortality. We had used another database for external validation. Results: A total of 1412 patients were enrolled, with an average age of 68.8 ± 15.9, including 708 (50.1%) males. When log-transformed RAR values were used as a continuous variable, as the values increases, the risk of death increases (30-day all-cause mortality OR = 4.02 (2.21, 7.32) P < 0.0001, ICU mortality OR = 3.81 (1.92, 7.54) P = 0.0001, and hospital mortality OR = 3.31 (1.83, 6.00) P < 0.0001), when the values were used as three-category variables and as a trend variable was also positively correlated with each mortality rate. Especially as the categorical variables, a dose-response relationship was clearly observed, that was, as the category of RAR increased (Q1 to Q3), the HR value of the risk of death gradually steadily increased. Such a relationship can also be observed in the external validation database. In the subgroup analysis, we observed an increased risk of death in the patient with hyperlipidemia and low HAS-BLED scores; however, no significant interaction was found in other subgroup analyses (including the diagnostic sequence of AIS). Conclusion: RAR was a predictor of mortality in AIS patients. However, more in-depth research is needed to further analyze and confirm the role of RAR in AIS patients.

Relationship between the red cell distribution width-to-platelet ratio and in-hospital mortality among critically ill patients with acute myocardial infarction: a retrospective analysis of the MIMIC-IV database.

OBJECTIVES: We aimed to investigate the association between red cell distribution width-to-platelet ratio (RPR), and in-hospital mortality in critically ill patients with acute myocardial infarction (AMI). DESIGN: A retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care database (MIMIC-IV) consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Centre in Boston. PARTICIPANTS: A total of 5067 patients with AMI were enrolled from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME: In-hospital mortality. RESULTS: A total of 4034 patients survived, while 1033 died. In a multiple regression analysis adjusted for age, weight and ethnicity, RPR also showed a positive correlation with in-hospital mortality (HR 1.91, 95% CI 1.42 to 2.56, p<0.0001). Moreover, after adjusting for additional confounding factors, obvious changes were observed (HR 1.63, 95% CI 1.03 to 2.57, p=0.0357). In model 2, the high ratio quartile remained positively associated with hospital mortality compared with the low ratio quartile (HR 1.20, 95% CI 1.01 to 1. 43), with a p-value trend of 0.0177. Subgroup analyses showed no significant effect modifications on the association between RPR and in-hospital mortality in the different AMI groups (p>0.05). CONCLUSION: RPR is an independent predictor of in-hospital mortality in critically ill patients with AMI.

Acute kidney disease in hospitalized acute kidney injury patients.

BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) have become worldwide public health problems, but little information is known about the epidemiology of acute kidney disease (AKD)-a state in between AKI and CKD. We aimed to explore the incidence and outcomes of hospitalized patients with AKD after AKI, and investigate the prognostic value of AKD in predicting 30-day and one-year adverse outcomes. METHODS: A total of 2,556 hospitalized AKI patients were identified from three tertiary hospitals in China in 2015 and followed up for one year.AKD and AKD stage were defined according to the consensus report of the Acute Disease Quality Initiative 16 workgroup. Multivariable regression analyses adjusted for confounding variables were used to examine the association of AKD with adverse outcomes. RESULTS: AKD occurred in 45.4% (1161/2556) of all AKI patients, 14.5% (141/971) of AKI stage 1 patients, 44.6% (308/691) of AKI stage 2 patients and 79.6% (712/894) of AKI stage 3 patients. AKD stage 1 conferred a greater risk of Major Adverse Kidney Events within 30 days (MAKE30) (odds ratio [OR], 2.36; 95% confidence interval 95% CI [1.66-3.36]) than AKD stage 0 but the association only maintained in AKI stage 3 when patients were stratified by AKI stage. However, compared with AKD stage 0, AKD stage 2-3 was associated with higher risks of both MAKE30 and one-year chronic dialysis and mortality independent of the effects of AKI stage with OR being 31.35 (95% CI [23.42-41.98]) and 2.68 (95% CI [2.07-3.48]) respectively. The association between AKD stage and adverse outcomes in 30 days and one year was not significantly changed in critically ill and non-critically ill AKI patients. The results indicated that AKD is common among hospitalized AKI patients. AKD stage 2-3 provides additional information in predicting 30-day and one-year adverse outcomes over AKI stage. Enhanced follow-up of renal function of these patients may be warranted.

Human umbilical cord-derived mesenchymal stem cells and human cord blood mononuclear cells protect against cisplatin-induced acute kidney injury in rat models.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are a promising tool to attenuate cisplatin (CP)-induced acute kidney injury (AKI). However, whether the transplantation of human cord blood mononuclear cells (hCBMNCs) exhibits similar protective effects and their potential underlying mechanisms of action remain unclear. The present study aimed to determine the protective effects of hUCMSCs and hCBMNCs transplantation therapies on an established CP-induced rat model and explore their underlying mechanisms of action. A total of 24 Sprague-Dawley rats, selected based on body weight, were randomly assigned into 4 groups: i) normal control; ii) model (CP); iii) hCBMNCs (CP + hCBMNCs); and iv) hUCMSCs (CP + hUCMSCs). hUCMSCs (2.0x106 cells) and hCBMNCs (2.0x106 cells) were injected into the femoral vein of rats 24 h after CP (8 mg/kg) treatment. To determine the effects of hCBMNCs and hUCMSCs on CP-induced rats, renal function assessment and histological evaluations were performed. Expression levels of high mobility group box 1 (HMGB1) and the ratio of Bax/Bcl2 in renal tissues were detected to elucidate their underlying molecular mechanisms of action. The results demonstrated that transplantation of hUCMSCs and hCBMNCs significantly improved renal function in CP-induced AKI rats, as evidenced by the enhancement of renal morphology; decreased concentrations of blood urea nitrogen and serum creatinine; and a lower percentage of apoptotic renal tubular cells. The expression of HMGB1 and the ratio of Bax/Bcl-2 were significantly reduced in the hUCMSCs and hCBMNCs groups compared with CP group. In conclusion, the present study indicated that hCBMNCs exert similar protective effects to hUCMSCs on CP-induced AKI. hUCMSCs and hCBMNCs protect against CP-induced AKI by suppressing HMGB1 expression and preventing cell apoptosis.

Novel risk models to predict acute kidney disease and its outcomes in a Chinese hospitalized population with acute kidney injury.

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427-2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862-0.896), AUROC2 = 0.845 (95% CI 0.813-0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells.

BACKGROUND: Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown. METHODS: The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway. RESULTS: An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells. CONCLUSION: All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway.

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

Post-contrast acute kidney injury in a hospitalized population: short-, mid-, and long-term outcome and risk factors for adverse events.

OBJECTIVES: To investigate the prognosis including major adverse kidney events within 30 days (MAKE30) and 90-day and 1-year adverse outcome in hospitalized patients with post-contrast acute kidney injury (PC-AKI) to identify high-risk factors. METHODS: This retrospective observational study included 288 PC-AKI patients selected from 277,898 patients admitted to hospitals from January 2015 to December 2015. PC-AKI was defined according to the 2018 guideline of European Society of Urogenital Radiology. Multivariable Cox regression and logistic regression analyses were used to analyze main outcome and risk factors. RESULTS: PC-AKI patients with AKI stage ≥ 2 had much higher incidence of MAKE30 than those with AKI stage 1 (RR = 7.027, 95% CI 4.918-10.039). Persistent renal dysfunction, heart failure, central nervous system failure, baseline eGFR < 60 mL/min/1.73 m2, oliguria or anuria, blood urea nitrogen ≥ 7.14 mmol/L, respiratory failure, and shock were independent risk factors of 90-day or 1-year adverse prognosis (p < 0.05). Compared with transient renal dysfunction, PC-AKI patients with persistent renal dysfunction had a higher all-cause mortality rate (RR = 3.768, 95% CI 1.612-8.810; RR = 4.106, 95% CI 1.765-9.551) as well as combined endpoints of death, chronic kidney disease, or end-stage renal disease (OR = 3.685, 95% CI 1.628-8.340; OR = 5.209, 95% CI 1.730-15.681) within 90 days or 1 year. CONCLUSIONS: PC-AKI is not always a transient, benign creatininopathy, but can result in adverse outcome. AKI stage is independently correlated to MAKE30 and persistent renal dysfunction may exaggerate the risk of long-term adverse events. KEY POINTS: • PC-AKI can result in adverse outcome such as persistent renal dysfunction, dialysis, chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. • AKI stage is independently correlated to MAKE30. • Persistent renal dysfunction may exaggerate the risk of long-term adverse events.

Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats.

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7(MMP-7)in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.

Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats.

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7 (MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.