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.

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.

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.

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.

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.

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.

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.

M2a and M2b macrophages predominate in kidney tissues and M2 subpopulations were associated with the severity of disease of IgAN patients.

M2 macrophages play important roles during the injury and repair phases in kidney. Our aims are to investigate the distribution of M2 subpopulations and the correlation with clinicopathological features of IgA nephropathy (IgAN) patients. In this study, renal samples from 49 IgAN patients were detected by immunofluorescence. The markers of M2 macrophages, including M2a (CD206+/CD68+), M2b (CD86+/CD68+) and M2c (CD163+/CD68+) were identified. We found M2a and M2b macrophages were the predominant subpopulations in kidney tissues of IgAN. M2a macrophages were mainly distributed in tubulointerstitium with renal lesions like segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis. However, there were larger numbers of M2c in glomeruli with minor lesions. Moreover, M2a and M2c macrophages were inversely correlated with the clinical and pathologic features, respectively. These results suggest M2 subpopulations were involved in the progression of IgAN, and M2a and M2c macrophages might show different properties to participate in the pathogenesis of IgAN.

Alternatively Activated Macrophages are Associated with Prostate Volume and Lower Urinary Tract Symptoms Severity of Patients with Benign Prostate Hyperplasia.

BACKGROUND: Recent studies show that alternatively activated macrophages (AAMs) are involved in tissue remodeling and fibrosis. However, the relationship between AAMs and the development of benign prostate hyperplasia (BPH) is unclear. The aim of this study is to investigate the correlation among AAMs, prostate volume, and lower urinary tract symptoms (LUTS) severity of benign prostate hyperplasia (BPH) patients. METHODS: Patients who underwent transurethral incision of the prostate (TUIP) for BPH were recruited and international prostatic symptom scores (IPSS) were assessed before the operations. Patients were divided into two groups: small (< 40 mL) and large prostate (≥ 40 mL) groups. Total macrophages (CD68) and AAMs (co-localization of CD68 and CD206) were analyzed by immunofluorescence. Prostate volume, post-voided residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rate were measured. We compared AAMs and clinical features between groups and analyzed the relationship of AAMs and these clinical parameters. RESULTS: A total of 42 patients diagnosed with BPH were recruited. The numbers of AAMs in prostate tissues of BPH patients with small prostate (n = 20) (5.15 ± 2.32 cells/HP) were significantly lower than those of large prostate (n = 22) (7.73 ± 2.83 cells/HP) (p < 0.05). Moreover, percentages of AAMs (AAMs/total macrophages) of small prostate patients (17.28 ± 6.62%) were lower than those of large prostate patients (23.30 ± 8.66%) (p < 0.05). Pearson's correlation analysis showed the numbers of AAMs were significantly positively correlated with prostate volume (r = 0.509, p < 0.01) and international prostatic symptom score (r = 0.344, p < 0.05). Percentages of AAMs were positively correlated with prostate volume (r = 0.447, p < 0.01). CONCLUSIONS: AAMs are associated the degree of BPH and the severity of LUTS, which indicates that AAMs may play an important role in development of BPH.

Risk Factors and Prognosis of Cardiorenal Syndrome Type 1 in Elderly Chinese Patients: A Retrospective Observational Cohort Study.

BACKGROUND/AIMS: Cardiorenal syndrome type 1 (CRS1) is a syndrome characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). The aims of this study were to investigate the risk factors and the prognosis of CRS1 in elderly patients. METHODS: A total of 312 elderly patients (≥60 years old) with acute heart failure (AHF) were studied. They were assigned as CRS1 (suffered from in-hospital AKI) or NCRS1 (without AKI) group. Clinical and laboratory data were recorded. Univariate and multivariate analysis were performed to clarify the risk factors for occurrence and mortality of CRS1 in this cohort. RESULTS: Incidence of CRS1 was 52.56%. Basic estimated glomerular filtration (eGFR <60 ml/(min.1.73m2) and use of diuretics were associated with the higher risk of CRS1 in elderly patients (OR=2.239, P=0.025; OR=2.555, P=0.001; respectively). Whereas higher concentration of serum albumin was protective factor for them (OR=0.907, P=0.007). The in-hospital mortality of CRS1 was 23.2%. Dialysis, use of beta blockers or diuretics were associated with all-cause death of CRS1 patients (OR=10.407, P<0.001; OR=0.312, P=0.011; OR=0.345, P=0.040; respectively). The in-hospital mortality of AHF patients was 13.1%. Higher Charlson comorbidity index, occurrence of CRS1 and dialysis were risk factors for in-hospital mortality of AHF patients (OR=4.723, P=0.041; OR=6.096, P=0.008; OR=18.743, P<0.001; respectively). CONCLUSIONS: Incidence of CRS1 in elderly patients is relatively high and associated with poor outcome. Reduced basic eGFR, lower serum albumin and use of diuretics are risk factors for the occurrence of CRS1 in elderly patients, while use of diuretics, beta blockers and dialysis during hospitalization are predictors of in-hospital mortality in patients with CRS1. These results above suggest that more suitable treatments for the elderly with CRS1 might be needed.

A retrospective analysis of kidney function and risk factors by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese patients.

Chronic kidney disease accounts for much of the increased mortality, especially in the elder population. The prevalence of this disease is expected to increase significantly as the society ages. Our aim was to evaluate the kidney function and risk factors of reduced renal function among elderly Chinese patients. This study retrospectively collected clinical data from a total of 1062 inpatients aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function and risk factors were also analyzed. For all 1062 subjects, the mean eGFR was 71.0 ± 24.8 mL/min/1.73 m(2), and the incidence rates of reduced renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6% and 8.7%, respectively. The eGFR values were 83.4 ± 28.4, 72.2 ± 22.9, 67.8 ± 24.3 and 58.8 ± 29.1 mL/min/1.73 m(2) in the groups of 60-69, 70-79, 80-89 and ≥90 years age group (F = 15.101, p = 0.000), respectively; while the incidences of reduced renal function were 12.8%, 27.0%, 37.8% and 51.7% (χ(2) = 36.143, p = 0.000). Binary logistic regression analysis showed that hyperuricemia (OR = 4.62, p = 0.000), proteinuria (OR = 3.96, p = 0.000), urinary tumor (OR = 2.92, p = 0.015), anemia (OR = 2.45, p = 0.000), stroke (OR = 1.96, p = 0.000), hypertension (OR = 1.83, p = 0.006), renal cyst (OR = 1.64, p = 0.018), female (OR = 1.54, p = 0.015), coronary artery disease (OR = 1.53, p = 0.008) and age (OR = 1.05, p = 0.000) were the risk factors of reduced renal function. In conclusion, eGFR values decreased by age, while the incidence of reduced renal function, proteinuria, hematuria and leukocyturia increased with age. Treatment and control of comorbidities may slow the decline of renal function in elderly patients.

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.

Smad7 gene transfer attenuates angiogenesis in peritoneal dialysis rats.

AIM: Transforming growth factor-ß (TGF-ß) has been shown to play a role in peritoneal angiogenesis associated with peritoneal dialysis (PD). The present study investigated whether blockade of TGF-ß signalling with Smad7 has a therapeutic effect on PD induced-peritoneal angiogenesis. METHODS: A rat model of peritoneal dialysis was induced by a daily intraperitoneal injection of 4.25% Dianeal and lipopolysaccharides. PD rats were transfected with a doxycycline regulated, Smad7-expressing plasmid using an ultrasound-microbubble-mediated system on day 0 and day 14 after initiation of PD and an empty vector was used as control. Peritoneal microvessel density (MVD) in peritoneal tissue was assessed by anti-CD31 immunohistochemistry after 4 weeks of PD and peritoneal angiogenic growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was also examined by immunofluorescence, western blot and reverse transcription-polymerase chain reaction. RESULTS: In contrast to the normal control group, at 4 weeks after PD, PD rats displayed peritoneal lesions, peritoneal angiogenesis and increased mRNA and protein expression of VEGF, bFGF and PDGF. Smad7 gene transfer significantly attenuated the peritoneal MVD and inhibited the upregulation of VEGF, bFGF and PDGF. Moreover, inhibition of peritoneal angiogenesis by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad3 and downregulation of TGF-ß expression. CONCLUSION: Smad7 gene transfer via an ultrasound-microbubble-mediated system is able to attenuate peritoneal angiogenesis in a rat model of PD. Those results suggest that blockade of the TGF-ß/Smad signalling pathway may represent a novel therapeutic approach to prevent PD-induced peritoneal angiogenesis.

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.

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.

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.

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.

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.

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.