Serum Cystatin C within 24 hours after admission: a potential predictor for acute kidney injury in Chinese patients with community acquired pneumonia.

BACKGROUND: Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP), and is associated with poor prognosis. Therefore, in this study, we evaluated whether AKI in Chinese patients with CAP could be well predicted by serum Cystatin C within 24 h after admission. METHODS: Univariate and multivariate logistic regression analyses were used to investigate independent factors of AKI in patients with CAP. RESULTS: Totally, 2716 patients with CAP were included in this study. 766 (28%) patients developed AKI. After multivariate logistic regression analysis, serum Cystatin C (odds ratio [OR] 4.27, 95% confidence interval [CI] 3.36-5.44; p < 0.001) was an independent factor for AKI in patients with CAP. Serum Cystatin C had an area under the receiver operating characteristic curve (AUC) of 0.81 for predicting AKI, with an optimal cutoff value of 1.37 mg/L, computing 68% sensitivity, 80% specificity. Furthermore, serum Cystatin C within 24 h after admission still had a good and stable prediction efficiency for AKI in various subgroups (age, gender, hypertension, diabetes, coronary artery disease, cardiac insufficiency, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, and tumor, albumin, anemia, platelet count, white blood cell count, and uric acid, confusion, uremia, respiratory rate, blood pressure, and age 65 years or older [CURB-65] score, acute respiratory failure, intensive care unit admission, and mechanical ventilation) of patients with CAP (AUCs: 0.69-0.84). CONCLUSION: Serum Cystatin C within 24 h after admission appears to be a good biomarker for predicting AKI in Chinese patients with CAP.

IKKα aggravates renal fibrogenesis by positively regulating the Wnt/ß-catenin pathway.

AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKα contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKα on TGF-ß1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKα was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKα was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKα-/- mice exhibited inactivated Wnt/ß-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-ß1-stimulated human tubular epithelial cells, IKKα overexpression enhanced ß-catenin nuclear translocation. Blocking IKKα by siRNA specifically suppressed ß-catenin activation and downstream profibrotic genes such as fibronectin and α-smooth muscle actin (α-SMA). Taken together, our study demonstrated that IKKα aggravated renal fibrogenesis by activating Wnt/ß-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis.

Association of Blood Selenium Level with Estimated Glomerular Filtration Rate in the Aging Population: a Cross-sectional Study.

The relationship between blood selenium level and estimated glomerular filtration rate (eGFR) had been explored in previous studies. However, there are few studies about the correlation between blood selenium level and eGFR in the elderly population. This study was undertaken to investigate the relationship between blood selenium level and eGFR in the aged. The present study was a cross-sectional study and used the National Health and Nutrition Examination Survey (NHANES) 2011-2018 dataset. We investigated the association between blood selenium level and eGFR among participants aged 60 years or older. Totally, 4423 participants were enrolled, and the average age was 69.7 ± 6.9 years old. The means of blood selenium level and eGFR were 192.9 ± 29.5 ug/L and 74.1 ± 19.9 mL/min/1.73 m2, respectively. After adjusting potential confounders (age, gender, body mass index, ethnicity, marital status, education, family income to poverty ratio, smoking, hypertension, and diabetes mellitus), non-linear relationship was detected between blood selenium level and eGFR, whose inflection point was 202 ug/L. The effect sizes (ß) and the confidence intervals on the left and right sides of inflection point were 0.07 (0.04 to 0.11) and 0.01 (- 0.02 to 0.04), respectively. In addition, subgroup analysis showed that blood selenium level was positively associated with eGFR, and the test for interactions was not statistically significant in various subgroups. In conclusion, the relationship between blood selenium level and eGFR is non-linear. Blood selenium level is positively related with eGFR when blood selenium level is less than 202 ug/L.

Interaction of Acute Respiratory Failure and Acute Kidney Injury on in-Hospital Mortality of Patients with Acute Exacerbation COPD.

PURPOSE: Both acute respiratory failure (ARF) and acute kidney injury (AKI) are two common complications in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Moreover, both ARF and AKI are reported as increasing the risk of mortality of patients with AECOPD. However, the interaction of ARF and AKI on the mortality of patients with AECOPD remains unknown. Therefore, the aim of this study is to investigate the joint effect of ARF and AKI on in-hospital mortality in AECOPD patients. PATIENTS AND METHODS: We performed a retrospective, observational cohort study of data from Nanjing First Hospital. The effect of AKI and ARF on in-hospital mortality was assessed using a multivariate logistic regression model. Additive interaction was assessed with the relative excess risk due to interaction. RESULTS: A total of 1647 participants were enrolled. ARF and AKI occurred in 515 (31.3%) and 357 (21.7%) patients, respectively. Overall, in-hospital mortality was 5.7%. The in-hospital mortality of the neither ARF nor AKI group, the ARF only group, the AKI only group, and both the ARF and AKI group were 0.8%, 7.0%, 7.5%, and 29.9%, respectively. After multivariate logistic regression analysis, the independent factors for in-hospital death included: albumin (OR 0.88, 95% CI 0.83-0.93, P < 0.001), ARF only (OR 8.53, 95% CI 3.64-19.99, P < 0.001), AKI only (OR 8.99, 95% CI 3.58-22.55, P < 0.001), and both ARF and AKI (OR 39.13, 95% CI 17.02-89.97, P < 0.001). The relative excess risk due to interaction was 22.62 (95% CI, 0.31 to 44.93), the attributable proportion due to interaction was 0.59 (95% CI, 0.36 to 0.79), and the synergy index was 2.46 (95% CI, 1.44 to 4.20), indicating ARF and AKI had a significant synergic effect on in-hospital mortality. CONCLUSION: ARF and AKI had a synergistic effect on in-hospital mortality in AECOPD patients.

Impact of acute kidney injury on in-hospital outcomes in Chinese patients with community acquired pneumonia.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear. METHODS: Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively. RESULTS: A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04-1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02-1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P < 0.001), mechanical ventilation (33.8% versus 9.3%; P < 0.001), invasive mechanical ventilation (25.9% versus 5.8%; P < 0.001), non-invasive mechanical ventilation (25.4% versus 7.1%; P < 0.001), and experienced a longer duration of hospital stay (14 days versus 10 days; P < 0.001) than those without AKI. However, no significant difference in ICU stay (11 days versus 10 days; P = 0.099) and duration of mechanical ventilation (8 days versus 8 days; P = 0.369) between AKI and non-AKI groups was found. CONCLUSION: AKI was common in Chinese patients with CAP. Patients with CAP who developed AKI had worse in-hospital outcomes.

Serum cystatin C: A potential predictor for hospital-acquired acute kidney injury in patients with acute exacerbation of COPD.

Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, p < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; p < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; p < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.

Is the Chronic Kidney Disease Epidemiology Collaboration four-level race equation better than the cystatin C equation?

AIM: To evaluate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) four-level race equation in the assessment of glomerular filtration rate (GFR) in Chinese people with chronic kidney disease (CKD), which was published in 2011, compared with the cystatin C-based GFR estimation equation (CysC GFR) and the combination of CysC and serum creatinine equation (CysC-Scr GFR). METHODS: The CKD-EPI four-level race equation estimated GFR (CKD-EPI GFR) was compared with the CysC GFR and CysC-Scr GFR. Three equations were compared with body surface area (BSA) standardized GFR (sGFR), which was measured by (99m) Tc-DTPA renal dynamic imaging method in 111 CKD cases. RESULTS: A statistically significant correlation was found between sGFR and CKD-EPI GFR, CysC GFR and CysC-Scr GFR. Three estimated GFR (eGFR) equations of 30% accuracy were 58.6%, 56.8% and 63.5%, respectively. Average deviations of eGFR from sGFR were 2.34, 1.19, and 1.32 (mL/min per 1.73 m(2)) (P > 0.05), respectively. There was no significant deviation in the CKD from stages 1 to 5 in CKD-EPI GFR and CysC-Scr GFR. However, when estimated by CysC GFR, the deviation was increased, with the value of 12.41 mL/min per 1.73 m(2) (P= 0.002) in CKD stage 5. CONCLUSION: Our results showed that in a Chinese population with CKD, CKD-EPI GFR, CysC GFR and CysC-Scr GFR of bias and overall accuracy of 30% were very similar. There was little advantage in adding Asian coefficient to modifying the CKD-EPI equation. CysC GFR overestimated GFR in patients with CKD stages 4 and 5.

Implication of CKD-EPI equation to estimate glomerular filtration rate in Chinese patients with chronic kidney disease.

OBJECTIVE: To evaluate the applicability of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in Chinese patients of different stages of CKD. METHODS: The CKD-EPI equation estimated GFR (eGFR) was compared with body surface area standardized GFR (sGFR), which was measured by diethylenetriaminepentaacetic acid renal dynamic imaging method in 142 CKD cases. RESULTS: eGFR was positively correlated with sGFR (r = 0.838, p < 0.001). eGFR of 15%, 30%, and 50% accuracy were 31.0%, 57.7%, and 76.8%, respectively. Average deviation of eGFR from sGFR was -0.92 ± 16.36 mL/min/1.73 m2 (p = 0.506). There was no significant deviation in the CKD from stages 2 to 5. However, in CKD stage 1, the deviation was increased with the value of 13.36 ± 18.44 mL/min/1.73 m(2) (p = 0.023). CONCLUSION: CKD-EPI equation might be widely used in evaluation of Chinese CKD patients of different stages, with a less deviation and higher accuracy. However, in CKD stage 1, eGFR was higher than sGFR on average. It was suggested that eGFR might be overcorrected or overestimated. These results demonstrated that careful modification of CKD-EPI equation would be necessary in Chinese populations with CKD.

Glycine-induced cytoprotection is mediated by ERK1/2 and AKT in renal cells with ATP depletion.

Glycine receptor (GlyR) activation by glycine protects cells against ATP depletion. However, the underlying mechanisms remain unclear. To define signaling pathways responsible for the GlyR mediated cytoprotection, we examined the phosphorylation status of key kinases signaling pathways in Madin-Darby canine kidney (MDCK) cells. Our results indicated that growing the ATP-depleted MDCK cells in glycine-containing media increased the level of phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2), Ets-like transcription factor-1 (Elk1), AKT, and Forkhead box O-class 1 (FoxO1), decreased the level of phosphorylated p38 mitogen-activated protein kinase, while having little effect on the phosphorylation status of c-Jun N-terminal kinase 1 and 2. Similar phosphorylation changes in these molecules took place in the GlyRα1 stably expressing HEK-293 cell. We also showed that treating MDCK cells with ERK1/2 inhibitor PD98059 or AKT inhibitor LY294002 diminished cytoprotection against cell death by glycine, as determined by assessment of lactate dehydrogenase release and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide activity. In contrast, treatment with p38 inhibitor SB203580 enhanced the glycine-induced cytoprotection. Finally, RNAi-mediated silencing of GlyRα1 abolished the glycine-induced changes in phosphorylation status of the above kinases in ATP-depleted cells. Taken together, our results suggest that the ERK1/2 and AKT signaling pathways are involved in the glycine-GlyR protection of MDCK cells against death induced by ATP depletion.