Publications by authors named "Mengqing Ma"

11 Publications

  • Page 1 of 1

Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury.

Gerontology 2021 Jun 15:1-9. Epub 2021 Jun 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Introduction: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI).

Methods: Wild-type (WT) mice and IDO knockout (IDO-/-) mice were divided into the sham group and acute kidney injury (AKI) group. Mice in the sham group underwent dorsal incision and exposure of renal pedicle without clamping renal artery, while mice in the AKI group received unique renal artery IRI, and the contralateral kidney was removed at day 13 after IRI. Blood and IRI kidneys were collected at day 14. Kidney function was analyzed by measuring serum Cr and BUN. Morphology was analyzed by tissue periodic acid-Schiff (PAS) staining and Masson staining. Further, fibrosis markers and Wnt/β-catenin pathway proteins were determined by Western blot. Prostaglandin E2 (PGE2) was administrated for 2 weeks after the IRI mice model was established to observe whether it ameliorates kidney fibrosis after IRI.

Results: WT AKI mice revealed elevated expression of IDO compared with WT sham mice. Kidney function of IDO-/- AKI mice showed better than that of WT AKI mice. PAS staining exhibited less loss of tubular epithelial cells and atrophy tubules in IDO-/- AKI mice. Furthermore, kidney fibrosis areas and the expressions of fibrosis markers, including α-SMA, fibronectin, and vimentin, were increased in WT AKI mice. In addition, GSK-3β and β-catenin were significantly declined in IDO-/- AKI mice. On top of that, PGE2 administration revealed inhibited IDO expression and that reducing GSK-3β and β-catenin resulting in lower expressions of α-SMA, fibronectin, and vimentin in WT AKI mice.

Conclusions: IRI could increase IDO expression to activate Wnt/β-catenin pathway resulting kidney fibrosis. PGE2 could ameliorate kidney fibrosis via inhibiting IDO expression.
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http://dx.doi.org/10.1159/000515041DOI Listing
June 2021

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

BMC Pulm Med 2021 May 1;21(1):143. Epub 2021 May 1.

Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China.

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.
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http://dx.doi.org/10.1186/s12890-021-01511-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088559PMC
May 2021

Effect of CRRT combined with low-flow ECMO on canines with ARDS and hypercapnia.

J Artif Organs 2021 Mar 9. Epub 2021 Mar 9.

Department of ICU, the First Affiliated Hospital of Hunan University of Medicine, Huaihua, 418000, Hunan, China.

To observe the effect of continuous renal replacement therapy (CRRT) combined with low-flow extracorporeal membrane oxygenation (ECMO) of V-V mode on anti-inflammation, improving oxygenation and reducing PCO in canines with acute respiratory distress syndrome (ARDS) and hypercapnia. A total of 30 healthy adult canines were randomly divided into sham group (n = 10), ECMO (EC) group (n = 10) and CRRT + ECMO (CR + EC) group (n = 10). Sham group was only treated with invasive mechanical ventilation. EC group was also treated with ECMO. CR + EC group was treated with CRRT combined with low-flow ECMO of V-V mode besides invasive mechanical ventilation. The results showed that hazard ratio was lower in the CR + EC group. Inflammatory factors, OI values, and PaCO levels were lower in the CR + EC group. There was no significant difference in the levels of MAP, CO and T among the three groups. No significant complications or death was developed in the three groups. Compared with ECMO group at T3, T6 and T9, IL-6 [(276.13 ± 8.32, 262.04 ± 7.15, 259.33 ± 7.31)ng/L VS (352.67 ± 19.24, 360.24 ± 23.58, 362.21 ± 25.24)ng/L] and TNF-α [(50.14 ± 1.75, 50.45 ± 1.81, 48.03 ± 1.24) ng/L VS (70.25 ± 3.02, 72.45 ± 3.25, 76.69 ± 2.18)ng/L] in CR + EC group were decreased (P < 0.0001). Compared with sham group, IL-6 [(343.76 ± 21.97, 345.91 ± 19.89, 340.34 ± 22.17)ng/L]and TNF-α [(68.10 ± 2.96, 67.31 ± 3.01, 70.34 ± 3.35)ng/L] of T3, T6 and T9 in CR + EC group were lower (P < 0.0001). These findings indicated that CRRT combined with low-flow ECMO of V-V mode had a positive effect on anti-inflammation, oxygenation improvement and surplus blood CO removal in canines with ARDS and hypercapnia. These results provide a promising treatment regimen for ARDS.
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http://dx.doi.org/10.1007/s10047-021-01253-9DOI Listing
March 2021

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

Chron Respir Dis 2020 Jan-Dec;17:1479973120940677

Department of Nephrology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

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%, < 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; < 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; < 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.
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http://dx.doi.org/10.1177/1479973120940677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493270PMC
September 2020

Incidence, Risk Factors, and Prognostic Implications of Acute Kidney Injury in Patients with Acute Exacerbation of COPD.

Int J Chron Obstruct Pulmon Dis 2020 15;15:1085-1092. Epub 2020 May 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Purpose: Little is known about the incidence, risk factors, and prognostic implications of acute kidney injury (AKI) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. In this study, we investigated the incidence, risk factors, and short-term outcomes of AKI in these patients.

Patients And Methods: We analyzed the records of 1768 patients admitted to Nanjing First Hospital with a principal diagnosis of AECOPD. Of these, 377 patients had AKI.

Results: AKI occurred in 377 patients (21%). Independent risk factors for AKI in patients with AECOPD were advanced age, coronary artery disease, anemia, cancer, chronic kidney disease, hypercapnic encephalopathy, acute respiratory failure, and mechanical ventilation. Patients with AKI had worse prognostic implications and were more likely to require mechanical ventilation (38.7% vs 19.1%, <0.001); non-invasive mechanical ventilation (38.2% vs 18.9%, <0.001); invasive mechanical ventilation (18.3% vs 3.1%, <0.001); intensive care unit (ICU) admission (33.7% vs 12.9%, <0.001); had a longer ICU stay (9 days vs 8 days, =0.033) and longer hospitalization (13 days vs 10 days, <0.001); and higher in-hospital mortality (18.0% vs 2.7%, <0.001) than those without AKI. Multivariable analysis indicated that compared to patients without AKI, those with stage 1, 2, or 3 AKI had a 1.9-fold, 2.1-fold, or 6.0-fold increased risk of in-hospital death, respectively.

Conclusion: AKI is common in patients with AECOPD requiring hospitalization. Patients with AKI have worse short-term outcomes. Thus, AKI may be a prognostic predictor of patient survival.
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http://dx.doi.org/10.2147/COPD.S238343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237118PMC
June 2021

Kidney injury induced by elevated histones in community-acquired pneumonia.

Mol Cell Biochem 2020 Aug 9;471(1-2):155-163. Epub 2020 Jun 9.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211166, Jiangsu, China.

Previous studies showed that extracellular histones could damage organs, but the role of extracellular histones in pneumonia patients with acute kidney injury (AKI) is unknown. This study aims to investigate the impact of extracellular histones on patients with community-acquired pneumonia (CAP) developed AKI. Blood samples were obtained within 24 h after admission to hospital from patients who were diagnosed with CAP. According to the discharge diagnosis, the patients were divided into 2 groups (Non-AKI and AKI). In vitro, A549 cells were treated with lipopolysaccharides (LPS) and conditioned media were collected. HK2 cells were exposed to the conditioned media or not. Cells proliferation and apoptosis of HK2 were determined. Clinically, Log Histones (OR 3.068; 95% CI 1.544-6.097, P = 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.945; 95% CI 0.914-0.978, P = 0.001) were predictors of AKI in CAP patients. Compared to the lower histones group, patients in the higher histones group were more likely to be admitted to ICU, receive mechanical ventilation, and have a longer length of in-hospital stay. In vitro, A549 cells injured by LPS released extracellular histones, in conditioned media which significantly promoted HK2 cells apoptosis. Extracellular histones was a high risk factor for developing AKI in CAP patients and a predictor of worse short-term outcomes. We also showed that extracellular histones in conditioned media damaged HK2 cells.Trial registration number: KY20181102-03; Date of registration: 20181102.
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http://dx.doi.org/10.1007/s11010-020-03775-xDOI Listing
August 2020

Renin-angiotensin-aldosterone system blockade is associated with higher risk of contrast-induced acute kidney injury in patients with diabetes.

Aging (Albany NY) 2020 04 2;12(7):5858-5877. Epub 2020 Apr 2.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, Jiangsu, China.

As the incidence of diabetes and cardiovascular comorbidities continues to rise, driven by increased prevalence of obesity and an aging population, so does the demand for percutaneous coronary intervention (PCI) to restore cardiac blood flow. Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly prescribed to hypertensive diabetic patients to prevent diabetic nephropathy. However, evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of contrast-induced acute kidney injury (CIAKI) following coronary angiography (CAG) and PCI. We therefore conducted a retrospective, multicenter study applying the propensity score matching method to evaluate the impact of RAAS inhibition on CIAKI in diabetic patients undergoing CAG/PCI. Among 2240 subjects that met the inclusion criteria, 704 patients in the ACEIs/ARBs group were successfully matched to eligible control patients. The incidence of CIAKI (serum creatinine increase ≥0.5 mg/dl or ≥25% from baseline within 72 h post-CAG/PCI) was significantly higher in the ACEIs/ARBs group than in the control group (26.6% vs. 16.2%, <0.001). However, control patients showed increased risk of overall adverse cardiovascular events (4.1% vs. 1.8% for ACEIs/ARBs; =0.016). These data indicate that RAAS inhibition increases the risk of CIAKI in diabetic patients, but confers protection against early cardiovascular events.
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http://dx.doi.org/10.18632/aging.102982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185147PMC
April 2020

Complement C3 and Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease Patients: A Pilot Study.

Kidney Blood Press Res 2020 22;45(1):61-69. Epub 2020 Jan 22.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China,

Context: Evidences have suggested complement C3 is a biomarker for nonalcoholic fatty liver disease (NAFLD) in the general population.

Objective: The present study was conducted to explore the predictive function of C3 for NAFLD in chronic kidney disease (CKD) patients.

Design, Setting, And Participants: CKD patients were recruited for evaluation of their liver function, kidney function, serum lipids, glycated hemoglobin, blood, and immune function. The glomerular filtration rate was calculated using the CKD-EPI equation. NAFLD was diagnosed according to predefined ultrasonographic criteria.

Results: A total of 648 consecutive CKD patients were included, with 216 (33.3%) patients diagnosed with NAFLD. The NAFLD group had significant higher levels of serum protein, serum albumin, triglycerides, glycated hemoglobin, complement C3, hemoglobin (p = 0.001), alanine aminotransferase (p = 0.002), estimated glomerular filtration rate (p = 0.007), and C4 (p = 0.043) and lower levels of cystatin C, β2-microglobulin, proteinuria (p = 0.001), and high-density lipoprotein cholesterol (p = 0.008). In a logistic regression model, only complement C3 (OR = 1.003; 95% CI 1.002-1.004, p = 0.001) was associated with a higher likelihood of being diagnosed with NAFLD. Finally, we constructed ROC curves for complement C3 for prediction of having NAFLD. The best cut-off for complement C3 was 993.5 mg/L and it yielded a sensitivity of 63.9% and a specificity of 70.1%.

Conclusion: Our study revealed that complement C3 can be used as a surrogate biomarker of NAFLD in CKD patients.
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http://dx.doi.org/10.1159/000504172DOI Listing
October 2020

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.

Biochem Biophys Res Commun 2019 04 13;512(2):163-169. Epub 2019 Mar 13.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Background: Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms.

Methods: We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed.

Results: The levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro.

Conclusions: RA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.
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http://dx.doi.org/10.1016/j.bbrc.2019.03.013DOI Listing
April 2019

mTOR and Beclin1: Two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury.

J Cell Physiol 2019 08 7;234(8):12562-12568. Epub 2019 Jan 7.

Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Autophagy is the general term of lysosomal degradation of substances in cells, which is considered the key to maintaining the normal structure and function of the heart. It also has a correlation with several heart diseases, in particular, myocardial ischemia/reperfusion (I/R) injury. At the stage of myocardial ischemia, autophagy degrades nonfunctional cytoplasmic proteins providing the critical nutrients for the critical life activities, thereby suppressing cell apoptosis and necrosis. However, autophagy is likely to affect the heart negatively in the reperfusion stage. Mammalian target of rapamycin (mTOR) and Beclin1 are two vital autophagy-related molecules in myocardial I/R injury playing significant roles in different stages. In the ischemia stage, mTOR plays its roles through AMPK/mTOR and phosphoinositide 3-kinase/Akt/mTOR pathway, whereas Beclin1 plays its roles through its upregulation in the reperfusion stage. A possible interaction between mTOR and Beclin1 has been reported recently, and further studies need to be done to find the underlying interaction between the two molecules in myocardial I/R injury.
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http://dx.doi.org/10.1002/jcp.28125DOI Listing
August 2019

The novel relationship between Sirt3 and autophagy in myocardial ischemia-reperfusion.

J Cell Physiol 2019 05 28;234(5):5488-5495. Epub 2018 Nov 28.

Cardiology Department, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, China.

Class III histone deacetylases (HDACs) belong to the proteasome family, comprising seven family members identified in mammalian cells, identified Sirt1-Sirt7. As an important member of HDACs, Sirt3 is hotly debated for its multiple functions. It was reported that Sirt3 got involved in the alleviation of multiple diseases, including myocardial infarction, neuron ischemia, hypertrophy, and diabetic myopathy. Through regulating many cellular mechanisms, such as apoptosis, autophagy, and clearance of reactive oxygen species (ROS), Sirt3 played an important role in the alleviation of myocardial ischemia-reperfusion injury. Nowadays Sirt3-induced autophagy was indicated to be involved in the process of the development of myocardial ischemia-reperfusion injury. Sirt3 could both activate and inhibit autophagy process by activating different downstream signal pathways, such as Sirt3-AMP-activated protein kinase pathway, Sirt3-Foxo3a pathway, and Sirt3-superoxide dismutase-mitochondrial ROS pathway. Whereas the Sirt3-induced autophagy in different phases of myocardial ischemia-reperfusion has not been systematically illustrated. In this review, we summarized the regulated mechanisms found in these years and listed the updated research about the relationship between Sirt3 and autophagy which are both positive and negative during myocardial ischemia-reperfusion phase. We anticipated that we may controlled the activation of autophagy by regulating the concentration of Sirt3 in myocyte. By maintaining a proper expression of autophagy in different phases of myocardial ischemia-reperfusion, we could reduce the morbidity of patients with myocardial infarction apparently in the future.
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http://dx.doi.org/10.1002/jcp.27329DOI Listing
May 2019
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