Causal effect of gut microbiota and diabetic nephropathy: a Mendelian randomization study.

BACKGROUND: The interaction of dysbiosis of gut microbiota (GM) with diabetic nephropathy (DN) drew our attention and a better understanding of GM on DN might provide potential therapeutic approaches. However, the exact causal effect of GM on DN remains unknown. METHODS: We applied two-sample Mendelian Randomization (MR) analysis, including inverse variance weighted (IVW), MR-Egger methods, etc., to screen the significant bacterial taxa based on the GWAS data. Sensitivity analysis was conducted to assess the robustness of MR results. To identify the most critical factor on DN, Mendelian randomization-Bayesian model averaging (MR-BMA) method was utilized. Then, whether the reverse causality existed was verified by reverse MR analysis. Finally, transcriptome MR analysis was performed to investigate the possible mechanism of GM on DN. RESULTS: At locus-wide significance levels, the results of IVW suggested that order Bacteroidales (odds ratio (OR) = 1.412, 95% confidence interval (CI): 1.025-1.945, P = 0.035), genus Akkermansia (OR = 1.449, 95% CI: 1.120-1.875, P = 0.005), genus Coprococcus 1 (OR = 1.328, 95% CI: 1.066-1.793, P = 0.015), genus Marvinbryantia (OR = 1.353, 95% CI: 1.037-1.777, P = 0.030) and genus Parasutterella (OR = 1.276, 95% CI: 1.022-1.593, P = 0.032) were risk factors for DN. Reversely, genus Eubacterium ventriosum (OR = 0.756, 95% CI: 0.594-0.963, P = 0.023), genus Ruminococcus gauvreauii (OR = 0.663, 95% CI: 0.506-0.870, P = 0.003) and genus Erysipelotrichaceae (UCG003) (OR = 0.801, 95% CI: 0.644-0.997, P = 0.047) were negatively associated with the risk of DN. Among these taxa, genus Ruminococcus gauvreauii played a crucial role in DN. No significant heterogeneity or pleiotropy in the MR result was found. Mapped genes (FDR < 0.05) related to GM had causal effects on DN, while FCGR2B and VNN2 might be potential therapeutic targets. CONCLUSIONS: This work provided new evidence for the causal effect of GM on DN occurrence and potential biomarkers for DN. The significant bacterial taxa in our study provided new insights for the 'gut-kidney' axis, as well as unconventional prevention and treatment strategies for DN.

A nomogram based on peripheral lymphocyte for predicting 8-year survival in patients with prostate cancer: a single-center study using LASSO-cox regression.

PURPOSE: The purpose of this study was to develop a functional clinical nomogram for predicting 8-year overall survival (OS) of patients with prostate cancer (PCa) primary based on peripheral lymphocyte. PATIENTS AND METHODS: Using data from a single-institutional registry of 94 patients with PCa in China, this study identified and integrated significant prognostic factors for survival to build a nomogram. The discriminative ability was measured by concordance index (C-index) and ROC curves (Receiver Operating Characteristic Curves). And the predictive accuracy was measured by the calibration curves. Decision curve analyses (DCA) was used to measure the clinical usefulness. RESULTS: A total of 94 patients were included for analysis. Five independent prognostic factors were identified by LASSO-Cox regression and incorporated into the nomogram: age, the T stage, the absolute counts of peripheral CD3(+)CD4(+) T lymphocytes, CD3(-)CD16(+)CD56(+) NK cells and CD4(+)/CD8(+) ratio. The area under the curve (AUC) values of the predictive model for 5-, 8-, and 10-year overall survival were 0.81, 0.76, and 0.73, respectively. The calibration curves for probability of 5-,8- and 10-year OS showed optimal agreement between nomogram prediction and actual observation. The stratification into different risk groups allowed significant distinction. DCA indicated the good clinical application value of the model. CONCLUSION: We developed a novel nomogram that enables personalized prediction of OS for patients diagnosed with PCa. This finding revealed a relative in age and survival rate in PCa, and a more favorable prognosis in patients exhibiting higher levels of CD4 + T, CD4+/CD8 + ratio and CD3(-)CD16(+)CD56(+) NK cells specifically. This clinically applicable prognostic model exhibits promising predictive capabilities, offering valuable support to clinicians in informed decision-making process.

Clinicopathological features and outcome in elderly patients with idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients. METHODS: A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65-83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People's Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed. RESULTS: Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m2 while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg's stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, p = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, p = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, p < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, p = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, p < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower (p < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment (p < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m2, p = 0.852). CONCLUSIONS: Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg's stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN.

The Long-Term Survival Outcome in Older Patients with Different Pathological Types of Chronic Kidney Disease.

INTRODUCTION: Chronic kidney diseases (CKDs) are prevalent in older people, and renal pathological manifestations are important for diagnosis, treatment, and prognosis. However, the long-term survival outcome and risk factors for older CKD patients with different pathological types are not fully understood and need to be further investigated. METHODS: Medical data were recorded and all-cause mortality was followed up in patients who underwent renal biopsy diagnosed in Guangdong Provincial People's Hospital from 2005 to 2015. Kaplan-Meier analysis was used to identify the incidence of survival outcomes. Multivariate Cox regression models and nomograms were applied to analyze pathological types and other factors for overall survival outcomes. RESULTS: 368 cases were included and the median follow-up was 85 (46.5, 111) months. Overall mortality was 35.6%. The highest mortality was in the mesangioproliferative glomerulonephritis (MPGN) group (88.9%), followed by amyloidosis (AMY) group (84.6%), and the lowest mortality was in the minimal change disease (MCD) group (21.9%). Moreover, multivariate Cox regression model showed that survival times of MPGN {hazard ratio (HR) = 8.215 (95% confidence interval [CI]: 2.735-24.674), p < 0.001} and AMY (HR = 6.130 [95% CI: 2.219-16.94], p < 0.001) were significantly shorter than MCD. In addition, age, lower baseline estimated glomerular filtration rate (eGFR), history of chronic obstructive pulmonary disease (COPD) and cerebrovascular accidents (CVA)/transient ischemic attack (TIA), MPGN, and AMY were independent risk factors for the mortality of older patients with CKD. CONCLUSION: The long-term survival outcome of older CKD patients showed differences among different pathological types, and MPGN, AMY, age, baseline eGFR, CVA/TIA, and COPD were independent predictors for mortality.

Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients.

Long-term peritoneal dialysis (PD) is associated with the development of peritoneal fibrosis (PF). Understanding the changes of immune environments and peritoneal mesothelial cells (PMCs) may lead to the discovery of mechanisms of PF. Therefore, we used single-cell RNA sequencing to interrogate cell composition and transcriptome characteristics in dialysate of continuous ambulatory PD (CAPD) patients at different stages. Results showed that six major cell populations were identified in overnight effluent dialysate. Two subsets of macrophages (Macro-c2-SSP1 and Macro-c5-FCN1&SSP1) and PMCs (HSPA1A + PMCs and RPL34 + PMCs) had the property of promoting fibrosis. Long-term patients had higher markers of cytotoxic CD8+T cells. Moreover, the expression levels of fibrosis-related genes were significantly increased and PMCs interacted closely with immune cells in the long-term group (p < 0.05). These data reveal new phenotypes and functional characteristics of immune cells and PMCs in dialysate of CAPD patients with different stages, which provide potential mechanisms and therapeutic strategies for PF.

Electronic Modulation of the 3D Architectured Ni/Fe Oxyhydroxide Anchored N-Doped Carbon Aerogel with Much Improved OER Activity.

It remains a big challenge to develop non-precious metal catalysts for oxygen evolution reaction (OER) in energy storage and conversion systems. Herein, a facile and cost-effective strategy is employed to in situ prepare the Ni/Fe oxyhydroxide anchored on nitrogen-doped carbon aerogel (NiFeOx(OH)y@NCA) for OER electrocatalysis. The as-prepared electrocatalyst displays a typical aerogel porous structure composed of interconnected nanoparticles with a large BET specific surface area of 231.16 m2·g-1. In addition, the resulting NiFeOx(OH)y@NCA exhibits excellent OER performance with a low overpotential of 304 mV at 10 mA·cm-2, a small Tafel slope of 72 mV·dec-1, and excellent stability after 2000 CV cycles, which is superior to the commercial RuO2 catalyst. The much enhanced OER performance is mainly derived from the abundant active sites, the high electrical conductivity of the Ni/Fe oxyhydroxide, and the efficient electronic transfer of the NCA structure. Density functional theory (DFT) calculations reveal that the introduction of the NCA regulates the surface electronic structure of Ni/Fe oxyhydroxide and increases the binding energy of intermediates as indicated by the d-band center theory. This work provides a new method for the construction of advanced aerogel-based materials for energy conversion and storage.

Cytoplasmic HMGB1 induces renal tubular ferroptosis after ischemia/reperfusion.

As a damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1) is well-studied and is released from injured tubular epithelial cells to trigger cell death. However, the role of intracellular HMGB1 induced cell death during acute kidney injury (AKI) is poorly understood. We showed that cytosolic HMGB1 induced ferroptosis by binding to acyl-CoA synthetase long-chain family member 4 (ACSL4), the driver of ferroptosis, following renal ischemia/reperfusion (I/R). Both mouse and human kidneys with acute tubular injury were characterized by nucleocytoplasmic translocation of HMGB1in tubular cells. Pharmacological inhibition of HMGB1 nucleocytoplasmic translocation and deletion of HMGB1 in tubular epithelial cells in mice inhibited I/R-induced AKI, tubular ferroptosis, and inflammation compared to those in controls. Co-immunoprecipitation and serial section staining confirmed the interaction between HMGB1 and ACSL4. Taken together, our results demonstrated that cytoplasmic HMGB1 is essential for exacerbating inflammation-associated cellular injury by activating renal tubular ferroptosis via ACSL4 after I/R injury. These findings indicate that cytoplasmic HMGB1 is a regulator of ferroptosis and a promising therapeutic target for AKI.

Comparison of estimated glomerular filtration rate equations based on serum creatinine-, cystatin C- and creatinine-cystatin C in elderly Chinese patients.

BACKGROUND: This study aimed to further evaluate the accuracy of eleven GFR equations in different subgroups of an elderly Chinese hospitalized population. METHODS: All participants of the study were divided into seven separate groups including age-subgroup, sex-subgroup, GFR Staging-subgroup and whether combined with diabetic, hypertensive, coronary heart disease (CHD) and cerebrovascular disease. Referring to Tc-99m-DTPA dual plasma sample clearance method, six serum creatinine (Cr)-based [Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr), Lund-Malmö Revised (LMR), Berlin Initiative Study (BIS1), Full Age Spectrum (FASCr) and European Kidney Function Consortium (EKFC)], two serum cystatin C(Cys)-based (CKD-EPICys and FASCys), and three Cr-Cys combination based (CKD-EPICr-Cys, BIS2 and FASCr-Cys) equations were employed. Bias, interquartile range of the median difference (IQR), P30, and GFR misclassification rate were calculated to compare the performance of the selected equations. RESULTS: A total of 359 elderly Chinese patients were enrolled. Overall, median mGFR was 36.91(25.26,56.32)ml/min/1.73 m2. Smaller biases (ml/min/1.73 m2) were shown in CKD-EPICr and BIS1 equations (0.75 and 0.61). IQR (ml/min/1.73m2) was least with BIS2 equation and FASCr-Cys equation (10.34 and 10.65). For accuracy (P30), performance of FASCr-Cys, BIS2, and BIS1 equation was superior (78.3%, 78.0%, and 74.7%, respectively). In terms of RMSE (ml/min/1.73 m2), BIS1 and FASCr-Cys equation performed better (12.44 and 12.51). CONCLUSIONS: Overall, this study showed that the eGFR equations were less accurate in the diabetic and non-hypertension group than in the non-diabetic and hypertension group, respectively. Among all enrolled equations, the BIS2 and FASCr-Cys equations might be the best choice to evaluate glomerular filtration rate in Chinese elderly patients.

B lymphocytes subpopulations are associated with cardiac remodeling in elderly patients with advanced chronic kidney disease.

AIM: Chronic Kidney Disease (CKD) is independently associated with increased cardiovascular disease (CVD) risk. The aim of this study was to investigate the potential roles of B lymphocyte populations with cardiac remodeling in elderly patients with advanced CKD. METHODS: We designed a retrospective study in a cohort of 167 patients (84 advanced CKD patients with stage 4-5 and 83 non-CKD controls). B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were identified by flow cytometry. Correlation of B cells subsets with cardiac remodeling and clinical data in elderly CKD patients were analyzed. RESULTS: In this study, we found that the prevalence of hypertension was more common in CKD patients than in the control subjects (P < 0.05). Spearman's analysis showed that CD19(+)CD5(+) B cells were negatively correlated with high sensitivity C-reactive protein (hsCRP), ß2-microglobulin (ß2-MG), serum creatinine (SCr), pro-brain natriuretic peptide (pro-BNP), high-sensitivity troponin T (TNT-hs), left ventricle end-diastolic dimension (LVDD), left ventricle end-systolic dimension (LVSD) and left ventricular mass (LVM), and CD19(+)CD5(-) B cells were negatively correlated with ß2-MG, SCr, pro-BNP and TNT-hs (P < 0.05). In contrary, left ventricular ejection fractions (LVEF) was positively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B cells (P < 0.05). In addition, patients with higher levels of CD19(+)CD5(+) B cells exhibited lower level of pro-BNP, TNT-hs, interventricular septum (IVS), LVSD and LVM (P < 0.05). Higher levels of CD19(+)CD5(-) B cells also presented lower levels of pro-BNP, TNT-hs and LVSD, but higher levels of LVEF (P < 0.05). Cox regression analysis showed that patients with higher levels of LVSD, lower CD19(+)CD5(+)and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05). CONCLUSIONS: Our results showed that CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were negatively correlated with ventricular hypertrophy-related echocardiographic parameters in advanced CKD patients, which indicated that B lymphocytes might be involved in pathogenesis and improve cardiac remodeling in CKD patients.

Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis.

BACKGROUND: Information on older patients with hospital-acquired acute kidney injury (HA-AKI) and use of drugs is limited. AIM: This study aimed to assess the clinical characteristics, drug uses, and in-hospital outcomes of hospitalized older patients with HA-AKI. METHODS: Patients aged ≥65 years who were hospitalized in medical wards were retrospectively analyzed. The study patients were divided into the HA-AKI and non-AKI groups based on the changes in serum creatinine. Disease incidence, risk factors, drug uses, and in-hospital outcomes were compared between the groups. RESULTS: Of 26,710 older patients in medical wards, 4,491 (16.8%) developed HA-AKI. Older patients with HA-AKI had higher rates of multiple comorbidities and Charlson Comorbidity Index score than those without AKI (p < 0.001). In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05). The proportions of patients with critical illness, use of nephrotoxic drugs, and the requirements of intensive care unit treatment, cardiopulmonary resuscitation, and dialysis as well as in-hospital mortality and hospitalization duration and costs were higher in the HA-AKI than the non-AKI group; these increased with HA-AKI severity (all p for trend <0.001). With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (p < 0.001). Moreover, HA-AKI incidence (adjusted odds ratio [OR], 10.26; 95% confidence interval (CI), 8.27-12.74; p < 0.001), and nephrotoxic drugs exposure (adjusted OR, 1.76; 95% CI, 1.63-1.91; p < 0.001) had an association with an increased in-hospital mortality risk. CONCLUSION: AKI incidence was high among hospitalized older patients. Older patients with HA-AKI had worse in-hospital outcomes and higher resource utilization. Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk.

Decreased B lymphocytes subpopulations are associated with higher atherosclerotic risk in elderly patients with moderate-to-severe chronic kidney diseases.

AIM: Cardiovascular diseases (CVD) are the leading cause of death in patients with chronic kidney disease (CKD), and the risk of CVD increases with reductions in renal function. This study aims to investigate the potential roles of B lymphocyte populations in subclinical atherosclerosis (measured by intima-media thickness, IMT) and prognosis in elderly patients with moderate-to-severe CKD. METHODS: In this study, a total of 219 patients (143 moderate-to-severe CKD patients with stage 3-4 and 76 non-CKD controls) were recruited. B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were analyzed by flow cytometry. Intima-media thickness (IMT) was measured by ultrasound. Correlations between the B cell subsets with IMT and clinical outcome was analyzed. RESULTS: CKD patients showed increased IMT (P = 0.006). The level of CD19(+)CD5(+) and CD19(+)CD5(-) B cells were decreased in CKD patients. Correlation analysis showed that IMT was positively correlated with systolic blood pressure, protein/creatinine ratio and diabetes (P < 0.05), and were negatively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes (P < 0.05). Stepwise multiple regression analysis showed that CD19(+)CD5(-) B cells had a significant independent association with IMT (P < 0.05). IMT was increased in lower level of total CD19(+) B cells (≤ 0.06 × 109 /L) and CD19(+)CD5(-) B cells (≤ 0.05 × 109 /L) (P < 0.05). Kaplan-Meier analysis showed that patients with lower levels of CD19(+)CD5(+) and CD19(+)CD5(-) B cells exhibited worse survival (P < 0.05). Cox regression analysis showed that patients with lower CD19(+)CD5(+) and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05). CONCLUSIONS: Our results showed that decreased CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were correlated with atherosclerosis and worse survival, which indicates that B lymphocytes might involve in atherosclerosis and associated the prognosis of elderly patients with moderate-to-severe CKD.

Applicability of Creatinine-based equations for estimating glomerular filtration rate in elderly Chinese patients.

BACKGROUND: The accuracy of the estimated glomerular filter rate (eGFR) in elderly patients is debatable. In 2020, a new creatinine-based equation by European Kidney Function Consortium (EKFC) was applied to all age groups. The objective of this study was to assess the appropriateness of the new EKFC equation with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Lund-Malmö Revised (LMR), Berlin Initiative Study 1 (BIS1), and full age spectrum (FAS) equations based on serum creatinine (SCR) for elderly Chinese patients. METHODS: A total of 612 elderly patients with a measured glomerular filtration rate (mGFR) by the dual plasma sample clearance method with Technetium-99 m-diethylenetriamine-pentaacetic acid (Tc-99 m-DTPA) were divided into four subgroups based on age, sex, mGFR, and whether combined with diabetes. The performance of GFR was assessed while considering bias, precision, accuracy, and root-mean-square error (RMSE). Bland-Altman plots, concordance correlation coefficients (CCCs), and correlation coefficients were applied to evaluate the validity of eGFR. RESULTS: The median age of the 612 participants was 73 years, and 386 (63.1%) were male. Referring to mGFR (42.1 ml/min/1.73 m2), the CKD-EPI, LMR, BIS1, FAS, and EKFC equations estimated GFR at 44.4, 41.1, 43.6, 41.8 and 41.9 ml/min/1.73 m2, respectively. Overall, the smallest bias was found for the BIS1 equation (- 0.050 vs. range - 3.015 to 0.795, P<0.05, vs. the CKD-EPI equation). Regarding P30, interquartile range (IQR), RMSE, and GFR category misclassification, the BIS1 equation generally performed more accurately than the other eqs. (73.9%, 12.7, 12.9, and 35.3%, respectively). Nevertheless, no equation achieved optimal performance for the mGFR≥60 ml/min/1.73 m2 subgroup. Bland-Altman analysis showed the smallest mean difference (- 0.3 ml/min/1.73 m2) for the BIS1 equation when compared to the other equations. CONCLUSIONS: This study suggested that the BIS1 equation was the most applicable for estimating GFR in Chinese elderly patients with moderate to severe renal impairment.

Clinical Characteristics and Risk Factors for Mortality in Older Patients with Dialysis-Receiving Community-Acquired Acute Kidney Injury.

INTRODUCTION: Older people in community are susceptible to acute kidney injury (AKI) and hemodialysis is the most important supportive measure used in the management of severe AKI. This study aims to investigate the clinical characteristics, outcomes and risk factors for mortality in older patients with dialysis-receiving-community-acquired AKI (CA-AKI). METHODS: A total of 1953 CA-AKI patients aged 65 years old and above were recruited from 2013 to 2016. Among which, 200 patients received hemodialysis. Clinical characteristics, outcomes, suspected nephrotoxic drug use after CA-AKI and risk factors for mortality in older CA-AKI patients with dialysis were analyzed. RESULTS: The percentage of CA-AKI patients receiving hemodialysis was 10.2%. Compared with non-dialysis patients, dialysis-receiving patients had more comorbidity, and worse renal function. The types of suspected nephrotoxic drugs used in dialysis patients were more than those in non-dialysis patients. Moreover, dialysis-receiving patients had worse outcomes, including complete recovery of renal function (42.0% vs 71.6%), intensive care unit (ICU) (69.0% vs 15.3%) transfer and in-hospital mortality (50.5% vs 5.6%) (P<0.01). Age, moderate/severe liver disease, beta lactam antibiotics, glycopeptide antibiotics, antifungal agents, drugs for anti-heart failure, category of suspected nephrotoxic drugs, hyperkalemia, increased leucocyte count, ICU transfer, multiple organ dysfunction (MODS), cardiogenic shock and cardio-pulmonary resuscitation (CPR) were risk factors for mortality by univariate logistic regression analysis. After adjusting for confounding factors, the independent risk factors were glycopeptide antibiotics, drugs for anti-heart failure, ICU transfer, MODS and CPR. CONCLUSION: The percentage of older CA-AKI patients receiving dialysis was high, and these patients had more comorbidity and worse prognosis. Glycopeptide antibiotics, drugs for anti-heart failure, ICU transfer, MODS and CPR were independent risk factors for mortality.

Hepatitis B Virus-Related Glomerulonephritis with Positive and Negative Serum HBsAg: Different Clinicopathologic Characteristics of Two Clinical Subtypes.

INTRODUCTION: The clinicopathologic characteristics of Hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with different serum HBsAg are not well known. This study aims to investigate the characteristics and treatments between HBV-GN patients with positive and negative serum HBsAg. METHODS: A retrospective review of patients with renal biopsies in Guangdong Provincial People's Hospital from 2005 to 2018 was performed. Clinicopathological data, treatments and remission of proteinuria were collected and compared between HBsAg+ and HBsAg- group. RESULTS: A total of 101 HBV-GN were recruited. Serum HBsAg+ and HBsAg- patients accounted for 62.4% and 37.6%, respectively. HBsAg+ group had poor kidney and liver functions. Pathological data showed the percentage of membranous nephropathy in HBsAg- group is significantly higher than that of HBsAg+ group (60.3% HBsAg+ vs 89.5% HBsAg-, P<0.05). Chronic renal tubular/interstitial injury was more prevalent in HBsAg+ group (16.9% HBsAg+ vs 2.6% HBsAg-, P<0.05). The deposition sites of immune complexes were significant different between the two groups. In addition, more HBsAg+ patients were given anti-HBV and less were given corticosteroid or immunosuppressants for treatment than that of HBsAg- patients. Percentages of clinical remission were increasing in both HBsAg+ and HBsAg- patients from 1, 3, 6 months to 1 year (18.75%, 45.2%, 67.8%, 82.4% vs 24.4%, 41.2%, 62.8%, 59.3%). The differences of remission betwen two groups were not significant (P>0.05). CONCLUSION: The clinicopathological characteristics and treatments of HBV-GN with serum HBsAg+ and HBsAg- were distinct, which indicated that the pathogenesis might be different and specific treatments were needed for HBV-GN patients with different serum HBsAg.

M2 Macrophage Subpopulations in Glomeruli Are Associated With the Deposition of IgG Subclasses and Complements in Primary Membranous Nephropathy.

Objectives: The role of M2 macrophages in the pathogenesis and progression of primary membranous nephropathy (PMN) remains unknown. In this study, we aimed to investigate the relationship between M2 subsets and clinicopathological features of patients with PMN. Methods: A total of 55 patients with PMN confirmed by biopsy were recruited. The clinical and pathological data were recorded, respectively. Immunohistochemistry was used to detect the markers of M2 macrophages, including total macrophages (CD68+), M2a (CD206+), M2b (CD86+) and M2c (CD163+). Results: The numbers of glomerular macrophages, M2a, M2b, and M2c macrophages were 1.83 (1.00, 2.67), 0.65 (0.15, 1.15), 0.67 (0.33, 1.50), and 0.80 (0.05, 2.30) per glomerulus, respectively. Higher number of glomerular macrophages was found in stage II compared with stage III (2.08 vs. 1.16, P = 0.008). These macrophages also were negatively correlated with serum albumin level (r = -0.331, P = 0.014), while positively associated with complement 3 (C3) deposition (r = 0.300, P = 0.026) and the severity of glomerulosclerosis (r = 0.276, P = 0.041). Moreover, glomerular M2a macrophages were significantly correlated with the deposition of C3 (r = 0.300, P = 0.026), immunoglobulin G1 (IgG1) (r = 0.339, P = 0.011), immunoglobulin G2 (IgG2) (r = 0.270, P = 0.046) and immunoglobulin G3 (IgG3) (r = 0.330, P = 0.014) in glomerular basement membrane (GBM). In addition, M2b macrophages were positively associated with IgG1 (r = 0.295, P = 0.029) and IgG2 (r = 0.393, P = 0.003), while M2c macrophages were negatively correlated with complement 4d (C4d) (r = -0.347, P = 0.009) in GBM. Conclusions: Our results showed that M2 macrophage subpopulations in glomeruli are associated with the deposition of IgG subclasses and complements in renal tissue of PMN, which indicate that M2 macrophages may be involved in the pathogenesis and progression of PMN. Moreover, M2a and M2c macrophages might show different tendencies in the pathogenesis of PMN.

The Incidence, Characteristics, and Use of Suspected Nephrotoxic Drugs in Elderly Patients with Community-Acquired Acute Kidney Injury.

PURPOSE: Acute kidney injury (AKI) is a major health problem with poor prognosis. However, little is known about elderly community-acquired-AKI (CA-AKI). This study aimed to investigate the incidence, clinical characteristics, outcomes and use of suspected nephrotoxic medications after CA-AKI in the elderly. MATERIALS AND METHODS: A total of 36,445 patients aged over 60 years were recruited from 2013 to 2016. Through an electronic database, we collected the demographic and medical history data, and admission lab results from all patients. RESULTS: A total of 2371 patients with CA-AKI were identified. The incidence of CA-AKI was 26.03% in the elderly. The proportion of CA-AKI patients with chronic comorbidities and Charlson comorbidity index score were higher than that of non-AKI patients. After CA-AKI, the proportions of exposure to non-steroidal anti-inflammatory drugs (NSAIDs), iodine contrast agent, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were significantly decreased (p < 0.001). However, the proportion of other possible nephrotoxic drugs (including aminoglycosides, glycopeptide antibiotics, antifungal agents, beta lactam antibiotics, diuretic, ferralia, adrenergic receptor agonists and drugs for cardiac insufficiency therapy) still increased after CA-AKI (p < 0.001). Compared with non-AKI patients, CA-AKI patients had higher percentage of cardiogenic shock, multiple organ failure, transferring to intensive care unit, cardio-pulmonary resuscitation, hemodialysis, and mortality (p < 0.001). Moreover, CA-AKI patients had worse prognosis when more kinds of suspected nephrotoxic drugs were used (p < 0.001). CONCLUSION: The incidence of CA-AKI in the elderly was high, with more complex chronic complications and poor clinical outcomes. The use of most suspected nephrotoxic drugs still increased and was associated with worse prognosis after CA-AKI.

Clinical features, risk factors, and clinical burden of acute kidney injury in older adults.

Background: Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study investigated the clinical features, risk factors, and clinical burden in this population. Methods: A retrospective observational study was performed with the clinical data of inpatients at Guangdong Geriatrics Institute from 1 August 2012, to 31 December 2016. AKI was classified into community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and the risk factors for AKI were ranked by weight. The relationships between AKI and adverse outcomes during hospitalization were analyzed using univariate and multivariate logistic regression. Results: In total, 6126 patients were enrolled, and 1704 patients developed AKI (27.8%): 6.3% had CA-AKI, and 21.5% had HA-AKI. In total, 1425 (23.3%), 202 (3.3%), and 77 (1.3%) patients had stage 1, 2 and 3 AKI, respectively. Age, dementia, moderate/severe renal disease, moderate/severe liver disease, metastatic solid tumor, female sex, congestive heart failure, chronic pulmonary disease, diabetes mellitus with chronic complications, non-metastatic tumor and lymphoma were independent risk factors for HA-AKI. The first five were also independent risk factors for CA-AKI. After multiple adjustment, AKI was associated with intensive care admission (CA-AKI: OR 5.688, 95% CI 3.122-10.361; HA-AKI: OR 4.704, 95% CI 3.023-7.298) and in-hospital mortality (CA-AKI: OR 5.073, 95% CI 2.447-10.517; HA-AKI: OR 13.198, 95% CI 8.133-21.419). Conclusion: AKI occurs in >25% of older adults in the geriatric ward. In addition to traditional risk factors, dementia and tumors were risk factors for AKI in older adults. AKI is closely related to a poor prognosis.

Transcription factor PU.1 and immune cell differentiation (Review).

The transcription factor PU.1, an important member of the ETS family, plays a significant role in the differentiation of immune cells, which include macrophages, neutrophils, dendritic cells, T lymphoid cells, B lymphoid cells and so on. Immune cells are involved in the occurrence and development of diseases, including inflammatory diseases, neoplastic diseases and immune diseases. Therefore, it is particularly crucial to elucidate the roles and mechanisms of PU.1 in immune cells. The elucidation of these mechanisms may lead to the development of more effective therapeutic strategies for the treatment of inflammatory diseases and immune­mediated diseases mediated by various immune cells. With the development of molecular biology, the mechanisms of PU.1 in immune cell differentiation have been further explained. Different levels of PU.1 expression determine the type of immune cell differentiation. PU.1 expression is increased during granulocyte and macrophage differentiation, while it is decreased during T lymphocyte and B lymphocyte differentiation. The present study reviews and discusses the effects of the transcription factor PU.1 on immune cell differentiation.

High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in vivo and in vitro.

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long­term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD­related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme­linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14­ and CCr7­positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14­ and CD206­positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high­glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration­dependent and time­dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor ß1 in the supernatant increased in a glucose concentration­dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD­related fibrosis.

Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

Aim: Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients. Methods: In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytometry to determine the following B cell subsets: total B cells (CD19+), innate B1 cells (CD19+CD5+), and conventional B2 cells (CD19+CD5-). Correlations between the B cell subsets with clinical features and patient prognosis were analyzed. Results: A total of 380 patients (mean age 82.29 ± 6.22 years, 76.3% male) were included. The median follow-up time was 37.0 months (range, 1-109 months); 109 (28.7%) patients died. The main causes of death were infections (59.6%) and cardiovascular diseases (22.9%). Correlation analysis showed that levels of serum creatinine (SCr), blood urea nitrogen (BUN), and CKD were negatively associated with B1 cells. However, lymphocytes, T lymphocytes, and estimated glomerular filtration rate (eGFR) were positively correlated with B1 cells (all P < 0.05). B2 cells were negatively associated with age, SCr, cystatin C, BUN, and CKD, and were positively correlated with hemoglobin, lymphocytes, T lymphocytes, NK cells, and eGFR (all P < 0.05). Patient survival was significantly better in patients with B cells > 0.05 × 109/L, B1 cells > 0.02 × 109/L, and B2 cells > 0.04 × 109/L. Multivariate Cox regression analysis showed that B1 cells > 0.02 × 109/L [hazard ratio (HR) = 0.502, 95% confidence interval (CI): 0.297-0.851, P = 0.010] and B2 cells > 0.04 × 109/L (HR = 0.536, 95% CI: 0.319-0.901, P = 0.019) were independent protective factors for all-cause mortality. Conclusions: Our results showed that B1 and B2 cells exhibited a significantly negative correlation with the progression of CKD in elderly patients. Moreover, B1 and B2 cells were independent prognostic factors for survival, which indicates that the decrease in B cells may be associated with the progression of kidney diseases.