cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28127800
title: Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production

description: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear. This study hypothesized that SGLT2i could alleviate diabetic kidney injury by inhibiting ferroptosis and explored its potential mechanisms. C57BL/6J mice were randomly divided into the control, DKD, DKD+dapagliflozin, and DKD+insulin treatment groups. Blood glucose levels and body weight were monitored. Renal function, tissue pathology, mitochondrial morphology and function, and lipid peroxidation biomarkers (lipid peroxidation [LPO], malondialdehyde [MDA], glutathione peroxidase 4 [GPX4], glutathione [GSH], and cystine transporter solute carrier family 7 member 11 [SLC7A11]) were evaluated. Human proximal tubule cells (HK2 cells) were exposed to high glucose alone or in combination with dapagliflozin. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, NAD+/NADH ratio (oxidized/reduced ratio of nicotinamide adenine dinucleotide), and lipid peroxidation were measured. In addition, the role of the β-hydroxybutyrate- Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (BHB-CaMKK2) axis in mediating dapagliflozin regulating ferroptosis was examined. Dapagliflozin significantly ameliorated kidney injury in mice with DKD. Typical changes in ferroptosis, including lipid peroxidation and impaired antioxidant capacity, increased in mice with DKD and HG-treated HK-2 cells. Dapagliflozin significantly improves ferroptosis-related lipid peroxidation and mitochondrial dysfunction. Furthermore, dapagliflozin suppressed the expression of CaMKK2, a key ferroptosis regulator. Specific CaMKK2 inhibitors alleviated mitochondrial damage and ferroptosis, whereas a CaMKK2 agonist counteracted the protective effects of dapagliflozin against mitochondrial, antioxidant, and anti-ferroptosis effects. In addition, dapagliflozin increased BHB production, which mediates its nephroprotective effects. Dapagliflozin improves DKD by inhibiting ferroptosis, promoting BHB production, and regulating CaMKK2. Dapagliflozin protects against diabetic kidney damage both <i>in vivo</i> and <i>in vitro</i>. Dapagliflozin is effective in attenuating diabetic kidney damage related ferroptosis. Dapagliflozin improves diabetic kidney disease by promoting β-hydroxybutyrate production. <b>Schematic diagram of the possible mechanism for the dapagliflozin protective effect on DKD.</b> Dapagliflozin improved DKD and lipid peroxidation by inhibiting ferroptosis through promoting BHB production and regulating CaMKK2, providing new mechanisms for protective effects of SGLT2i on DKD.
DOI: 10.6084/m9.figshare.28127800.v1
title: Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production

description: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear. This study hypothesized that SGLT2i could alleviate diabetic kidney injury by inhibiting ferroptosis and explored its potential mechanisms. C57BL/6J mice were randomly divided into the control, DKD, DKD+dapagliflozin, and DKD+insulin treatment groups. Blood glucose levels and body weight were monitored. Renal function, tissue pathology, mitochondrial morphology and function, and lipid peroxidation biomarkers (lipid peroxidation [LPO], malondialdehyde [MDA], glutathione peroxidase 4 [GPX4], glutathione [GSH], and cystine transporter solute carrier family 7 member 11 [SLC7A11]) were evaluated. Human proximal tubule cells (HK2 cells) were exposed to high glucose alone or in combination with dapagliflozin. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, NAD+/NADH ratio (oxidized/reduced ratio of nicotinamide adenine dinucleotide), and lipid peroxidation were measured. In addition, the role of the β-hydroxybutyrate- Calcium/Calmodulin Dependent Protein Kinase Kinase 2 (BHB-CaMKK2) axis in mediating dapagliflozin regulating ferroptosis was examined. Dapagliflozin significantly ameliorated kidney injury in mice with DKD. Typical changes in ferroptosis, including lipid peroxidation and impaired antioxidant capacity, increased in mice with DKD and HG-treated HK-2 cells. Dapagliflozin significantly improves ferroptosis-related lipid peroxidation and mitochondrial dysfunction. Furthermore, dapagliflozin suppressed the expression of CaMKK2, a key ferroptosis regulator. Specific CaMKK2 inhibitors alleviated mitochondrial damage and ferroptosis, whereas a CaMKK2 agonist counteracted the protective effects of dapagliflozin against mitochondrial, antioxidant, and anti-ferroptosis effects. In addition, dapagliflozin increased BHB production, which mediates its nephroprotective effects. Dapagliflozin improves DKD by inhibiting ferroptosis, promoting BHB production, and regulating CaMKK2. Dapagliflozin protects against diabetic kidney damage both <i>in vivo</i> and <i>in vitro</i>. Dapagliflozin is effective in attenuating diabetic kidney damage related ferroptosis. Dapagliflozin improves diabetic kidney disease by promoting β-hydroxybutyrate production. <b>Schematic diagram of the possible mechanism for the dapagliflozin protective effect on DKD.</b> Dapagliflozin improved DKD and lipid peroxidation by inhibiting ferroptosis through promoting BHB production and regulating CaMKK2, providing new mechanisms for protective effects of SGLT2i on DKD.
DOI: 10.6084/m9.figshare.28341502
title: IgG expressed by renal tubular epithelial cells in epithelial mesenchymal transformation and interstitial fibrosis in diabetic kidney disease

description: Studies have reported that immunoglobulin G (IgG) "deposited" in the basement membrane of renal tubules is associated with tubulointerstitial damage in patients with diabetic kidney disease (DKD). Our previous study found that renal tubular epithelial cells (RTECs) can express and secrete IgG (RTEC-IgG) which may be associated with fibrosis. The present study aimed to explore the role of RTEC-IgG in renal tubulointerstitial fibrosis (TIF) in DKD. The results showed that RTEC-IgG expression was up-regulated in the renal tubulointerstitium of DKD patients and was associated with worse kidney function, more severe anemia, and higher interstitial fibrosis and tubular atrophy (IFTA) scores, and positively correlated with tubular epithelial mesenchymal transition (EMT) and TIF. IgG expression was also enhanced in the renal tubulointerstitium of DKD mice, which was positively correlated with TIF. High glucose induced an over expression of IgG in human renal tubular epithelial cells, and knockdown of IgG with siRNA relieved the expression of α-smooth muscle actin (SMA), collagen IV, fibronectin, and transforming growth factor (TGF)-β1 under high glucose conditions. In conclusion, our study suggests that RTEC-IgG is involved in the development of DKD by promoting EMT and interstitial fibrosis via TGF-β1.
DOI: 10.6084/m9.figshare.28341502.v1
title: IgG expressed by renal tubular epithelial cells in epithelial mesenchymal transformation and interstitial fibrosis in diabetic kidney disease

description: Studies have reported that immunoglobulin G (IgG) "deposited" in the basement membrane of renal tubules is associated with tubulointerstitial damage in patients with diabetic kidney disease (DKD). Our previous study found that renal tubular epithelial cells (RTECs) can express and secrete IgG (RTEC-IgG) which may be associated with fibrosis. The present study aimed to explore the role of RTEC-IgG in renal tubulointerstitial fibrosis (TIF) in DKD. The results showed that RTEC-IgG expression was up-regulated in the renal tubulointerstitium of DKD patients and was associated with worse kidney function, more severe anemia, and higher interstitial fibrosis and tubular atrophy (IFTA) scores, and positively correlated with tubular epithelial mesenchymal transition (EMT) and TIF. IgG expression was also enhanced in the renal tubulointerstitium of DKD mice, which was positively correlated with TIF. High glucose induced an over expression of IgG in human renal tubular epithelial cells, and knockdown of IgG with siRNA relieved the expression of α-smooth muscle actin (SMA), collagen IV, fibronectin, and transforming growth factor (TGF)-β1 under high glucose conditions. In conclusion, our study suggests that RTEC-IgG is involved in the development of DKD by promoting EMT and interstitial fibrosis via TGF-β1.
DOI: 10.6084/m9.figshare.28620895
title: Frailty transitions and risk of chronic kidney disease: insights from the China Health and Retirement Longitudinal Study

description: Frailty is increasingly recognized as a critical factor in the risk of chronic kidney disease (CKD), and it is also a condition that can undergo transitions. However, the relationship between frailty transitions and CKD risk in aging populations remains underexplored. This study aims to investigate the association between frailty transitions and CKD risk in middle-aged and older adults using data from the China Health and Retirement Longitudinal Study. Frailty was assessed using a 40-item Frailty Index (FI), with participants categorized into three groups: robust (FI ≤ 0.10), pre-frail (0.10 &lt; FI ≤ 0.21), and frail (FI &gt; 0.21). Frailty transitions were tracked between the first and second waves of the study. Data on CKD incidence were obtained from self-reported physician-diagnosed kidney disease. Cox proportional hazards models were employed to evaluate the risk of CKD, with adjustments made for potential confounders. Among 12,050 participants (52.60% female, mean age 58.37), those who progressed to frailty or pre-frailty had an increased risk of CKD compared with stable participants (HR 1.74, <i>p</i> &lt; 0.001). In contrast, individuals who recovered from frailty to robust or pre-frail status had a reduced CKD risk (HR 0.71, <i>p</i> = 0.023). The results of the sensitivity analysis, which showed consistent findings, support the reliability of the results. Frailty transitions are significantly associated with the risk of CKD. Worsening frailty is linked to an increased risk of CKD, while improvement in frailty is associated with a lower risk of CKD.
DOI: 10.6084/m9.figshare.28620895.v1
title: Frailty transitions and risk of chronic kidney disease: insights from the China Health and Retirement Longitudinal Study

description: Frailty is increasingly recognized as a critical factor in the risk of chronic kidney disease (CKD), and it is also a condition that can undergo transitions. However, the relationship between frailty transitions and CKD risk in aging populations remains underexplored. This study aims to investigate the association between frailty transitions and CKD risk in middle-aged and older adults using data from the China Health and Retirement Longitudinal Study. Frailty was assessed using a 40-item Frailty Index (FI), with participants categorized into three groups: robust (FI ≤ 0.10), pre-frail (0.10 &lt; FI ≤ 0.21), and frail (FI &gt; 0.21). Frailty transitions were tracked between the first and second waves of the study. Data on CKD incidence were obtained from self-reported physician-diagnosed kidney disease. Cox proportional hazards models were employed to evaluate the risk of CKD, with adjustments made for potential confounders. Among 12,050 participants (52.60% female, mean age 58.37), those who progressed to frailty or pre-frailty had an increased risk of CKD compared with stable participants (HR 1.74, <i>p</i> &lt; 0.001). In contrast, individuals who recovered from frailty to robust or pre-frail status had a reduced CKD risk (HR 0.71, <i>p</i> = 0.023). The results of the sensitivity analysis, which showed consistent findings, support the reliability of the results. Frailty transitions are significantly associated with the risk of CKD. Worsening frailty is linked to an increased risk of CKD, while improvement in frailty is associated with a lower risk of CKD.
DOI: 10.6084/m9.figshare.28201969
title: Early and high-volume administration of sodium bicarbonate in sepsis-associated acute kidney injury in patients with malignancies, during continuous renal replacement therapy

description: Sepsis is an uncontrolled systemic response to infection that leads to life-threatening organ dysfunction. The in-hospital mortality rate remains significantly high in septic shock patients with malignancies. This study investigates whether early and high-volume administration of sodium bicarbonate during continuous renal replacement therapy (CRRT) can reduce 28-day mortality, increase shock reversal rates, and shorten the duration of CRRT, mechanical ventilation, and intensive care unit (ICU) stays. The goal is to provide valuable clinical data for the management of cancer patients with sepsis-associated acute kidney injury (SAKI). A retrospective study was performed on 88 patients who were admitted to the ICU and received continuous renal replacement therapy (CRRT) for acute renal failure secondary to sepsis at the Cancer Center of Sun Yat-sen University from March 2010 to October 2021. Based on the initiation time of CRRT and the volume of sodium bicarbonate infusion, patients were divided into four groups: the early high-volume group, early low-volume group, late high-volume group, and late low-volume group. The results of this study showed that in the 28-day mortality model, established using the Cox proportional hazards method, early CRRT (HR 0.473; 95% CI 0.245–0.915, <i>p</i> = 0.026) and high-volume sodium bicarbonate infusion (HR 0.173; 95% CI 0.078–0.383, <i>p</i> &lt; 0.001) were identified as two independent protective factors. The 28-day mortality rate in the early high-volume group (15.0%) was significantly lower than that of the other three groups (60.0%, 30.0%, and 75.0%, respectively; <i>χ</i><sup>2</sup> = 23.822, <i>p</i> &lt; 0.001). Additionally, the shock reversal rate in the early high-volume group (80.0%) was significantly higher compared to the other groups (35.0%, 45.0%, and 35.7%; <i>χ</i><sup>2</sup> =13.576, <i>p</i> = 0.004). The duration of CRRT was shorter in the early high-volume group (35.0 ± 4.45 h) than in the other groups (70.0 ± 30.19 h, 48.0 ± 5.22 h, and 72.0 ± 19.84 h; <i>χ</i><sup>2</sup> =11.278, <i>p</i> = 0.01). Furthermore, the duration of mechanical ventilation (7.0 ± 3.33 days) was lower in the early high-volume group compared to the other groups (8.0 ± 1.12 days,10.0 ± 1.11 days, and 8.0 ± 2.65 days; <i>χ</i><sup>2</sup> =8.064, <i>p</i> = 0.045), as was the length of ICU stay (7.0 ± 0.89 days) compared to the other groups (13.0 ± 3.35 days, 10.0 ± 1.49 days, and10.0 ± 3.70 days; <i>χ</i><sup>2</sup> = 9.184, <i>p</i> = 0.027). Early and high-volume administration of sodium bicarbonate during CRRT may reduce 28-day mortality and improve shock reversal rates in patients with sepsis-associated acute kidney injury complicated by malignancy. Prospective randomized controlled large sample studies are needed to confirm this.
DOI: 10.6084/m9.figshare.28201969.v1
title: Early and high-volume administration of sodium bicarbonate in sepsis-associated acute kidney injury in patients with malignancies, during continuous renal replacement therapy

description: Sepsis is an uncontrolled systemic response to infection that leads to life-threatening organ dysfunction. The in-hospital mortality rate remains significantly high in septic shock patients with malignancies. This study investigates whether early and high-volume administration of sodium bicarbonate during continuous renal replacement therapy (CRRT) can reduce 28-day mortality, increase shock reversal rates, and shorten the duration of CRRT, mechanical ventilation, and intensive care unit (ICU) stays. The goal is to provide valuable clinical data for the management of cancer patients with sepsis-associated acute kidney injury (SAKI). A retrospective study was performed on 88 patients who were admitted to the ICU and received continuous renal replacement therapy (CRRT) for acute renal failure secondary to sepsis at the Cancer Center of Sun Yat-sen University from March 2010 to October 2021. Based on the initiation time of CRRT and the volume of sodium bicarbonate infusion, patients were divided into four groups: the early high-volume group, early low-volume group, late high-volume group, and late low-volume group. The results of this study showed that in the 28-day mortality model, established using the Cox proportional hazards method, early CRRT (HR 0.473; 95% CI 0.245–0.915, <i>p</i> = 0.026) and high-volume sodium bicarbonate infusion (HR 0.173; 95% CI 0.078–0.383, <i>p</i> &lt; 0.001) were identified as two independent protective factors. The 28-day mortality rate in the early high-volume group (15.0%) was significantly lower than that of the other three groups (60.0%, 30.0%, and 75.0%, respectively; <i>χ</i><sup>2</sup> = 23.822, <i>p</i> &lt; 0.001). Additionally, the shock reversal rate in the early high-volume group (80.0%) was significantly higher compared to the other groups (35.0%, 45.0%, and 35.7%; <i>χ</i><sup>2</sup> =13.576, <i>p</i> = 0.004). The duration of CRRT was shorter in the early high-volume group (35.0 ± 4.45 h) than in the other groups (70.0 ± 30.19 h, 48.0 ± 5.22 h, and 72.0 ± 19.84 h; <i>χ</i><sup>2</sup> =11.278, <i>p</i> = 0.01). Furthermore, the duration of mechanical ventilation (7.0 ± 3.33 days) was lower in the early high-volume group compared to the other groups (8.0 ± 1.12 days,10.0 ± 1.11 days, and 8.0 ± 2.65 days; <i>χ</i><sup>2</sup> =8.064, <i>p</i> = 0.045), as was the length of ICU stay (7.0 ± 0.89 days) compared to the other groups (13.0 ± 3.35 days, 10.0 ± 1.49 days, and10.0 ± 3.70 days; <i>χ</i><sup>2</sup> = 9.184, <i>p</i> = 0.027). Early and high-volume administration of sodium bicarbonate during CRRT may reduce 28-day mortality and improve shock reversal rates in patients with sepsis-associated acute kidney injury complicated by malignancy. Prospective randomized controlled large sample studies are needed to confirm this.
DOI: 10.6084/m9.figshare.28426990
title: Long-term outcomes of refractory central venous occlusive disease treated by stent deployment in patients undergoing maintenance hemodialysis

description: To investigate the long-term outcomes of stent deployment in the treatment of refractory central venous occlusive disease (CVOD) in patients undergoing maintenance hemodialysis (MHD). MHD patients who were successfully treated with stenting for symptomatic CVOD that was resistant to balloon angioplasty alone were consecutively included in this retrospective study. The primary (PPR) and assisted (APR) patency rates of the central vein and hemodialysis vascular access (VA), reintervention, and survival rates after stenting were followed. Multivariate logistic regression analyses were conducted to determine the factors influencing VA abandonment and mortality. The cohort comprised 65 patients (52.3% male) aged 61.5 ± 13.5 years, with a mean dialysis vintage of 54.7 ± 39.1 months. During 40 (20–54) months of follow-up, symptomatic CVOD recurred in 32 (49.2%) patients, accounting for 51 secondary angioplasties, including 34 stenting procedures. The PPR and APR at 12, 24, 36, 48, and 60 months were 81%, 52%, 47%, 41%, and 41% and 98%, 98%, 82%, 82%, and 82%, respectively. VA abandonment was noted in 10 (15.4%) patients. Six (9.2%) and 17 (26.2%) patients died due to cardiovascular conditions and all causes, respectively. The number of secondary stenting procedures was significantly associated with decreased VA abandonment [odds ratio (OR) = 0.089, 95% confidence interval (CI): 0.008–0.992, <i>p</i> = 0.049] and all-cause mortality (OR = 0.104, 95% CI: 0.011–0.947, <i>p</i> = 0.045). Angioplasty with stenting is an effective and promising strategy for MHD patients with refractory CVOD.
DOI: 10.6084/m9.figshare.28426990.v1
title: Long-term outcomes of refractory central venous occlusive disease treated by stent deployment in patients undergoing maintenance hemodialysis

description: To investigate the long-term outcomes of stent deployment in the treatment of refractory central venous occlusive disease (CVOD) in patients undergoing maintenance hemodialysis (MHD). MHD patients who were successfully treated with stenting for symptomatic CVOD that was resistant to balloon angioplasty alone were consecutively included in this retrospective study. The primary (PPR) and assisted (APR) patency rates of the central vein and hemodialysis vascular access (VA), reintervention, and survival rates after stenting were followed. Multivariate logistic regression analyses were conducted to determine the factors influencing VA abandonment and mortality. The cohort comprised 65 patients (52.3% male) aged 61.5 ± 13.5 years, with a mean dialysis vintage of 54.7 ± 39.1 months. During 40 (20–54) months of follow-up, symptomatic CVOD recurred in 32 (49.2%) patients, accounting for 51 secondary angioplasties, including 34 stenting procedures. The PPR and APR at 12, 24, 36, 48, and 60 months were 81%, 52%, 47%, 41%, and 41% and 98%, 98%, 82%, 82%, and 82%, respectively. VA abandonment was noted in 10 (15.4%) patients. Six (9.2%) and 17 (26.2%) patients died due to cardiovascular conditions and all causes, respectively. The number of secondary stenting procedures was significantly associated with decreased VA abandonment [odds ratio (OR) = 0.089, 95% confidence interval (CI): 0.008–0.992, <i>p</i> = 0.049] and all-cause mortality (OR = 0.104, 95% CI: 0.011–0.947, <i>p</i> = 0.045). Angioplasty with stenting is an effective and promising strategy for MHD patients with refractory CVOD.
DOI: 10.6084/m9.figshare.29039750
title: Inflammatory markers mediate association of AIP with kidney failure risk: data from National Health and Nutrition Examination Survey (NHANES) 2005–2018

description: Dyslipidemia and inflammation often coexist in the progression of kidney failure, with the atherosclerosis index of plasma (AIP) serving as a valuable marker for monitoring dyslipidemia. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018, involving a total of 10,358 participants. AIP was calculated as the logarithmic ratio (base 10) of triglycerides to high-density lipoprotein cholesterol (log10[TG/HDL-C]), while kidney failure was assessed through self-reported physician diagnosis. Logistic regression models and restricted cubic splines (RCS) were utilized to examine the association between AIP and the risk of kidney failure, with additional subgroup analyses performed to explore potential interactions. Mediation analyses were conducted to investigate whether inflammatory markers mediated the relationship between AIP and kidney failure. In logistic regression, after adjusting for all covariates, AIP was found to be positively associated with the risk of kidney failure [OR = 1.74 (95% CI: 1.04–2.92)], and a linear relationship between AIP and kidney failure risk was observed (P-non-linear = 0.4050). Mediation analysis revealed that segmented neutrophils, eosinophils, and monocytes partially mediated the association between AIP and kidney failure, with mediation proportions of 19.65%, 2.44%, and 7.25%, respectively. These findings suggest that Higher AIP was associated with an increased risk of kidney failure, with segmented neutrophils, eosinophils, and monocytes serving as partial mediators. The results provide valuable insights into the role of inflammation in kidney failure and highlight potential avenues for its prevention.