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1.
Ren Fail ; 46(2): 2398826, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39248402

RESUMO

BACKGROUND: During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation. METHODS: 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m2), chronic dialysis for at least 6 months, or renal transplantation. RESULTS: In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan-Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p = 0.778; composite kidney outcome, before 48 months, p = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p = 0.029). CONCLUSIONS: IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.


Assuntos
Taxa de Filtração Glomerular , Glomerulonefrite por IGA , Proteinúria , Humanos , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/terapia , Feminino , Masculino , Proteinúria/etiologia , Estudos Retrospectivos , Adulto , China/epidemiologia , Prognóstico , Pessoa de Meia-Idade , Estimativa de Kaplan-Meier , Indução de Remissão , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Diálise Renal , Adulto Jovem , Transplante de Rim , População do Leste Asiático
2.
Ren Fail ; 46(2): 2384585, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39252179

RESUMO

OBJECTIVES: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients. METHODS: In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months). RESULTS: Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate. CONCLUSION: Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04799067.


Assuntos
Hiperpotassemia , Falência Renal Crônica , Diálise Renal , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/efeitos adversos , China/epidemiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Idoso , Adulto , Poliestirenos/uso terapêutico , Poliestirenos/efeitos adversos , Silicatos/uso terapêutico , Recidiva , Potássio/sangue , Prevalência , População do Leste Asiático
3.
Kidney Int Rep ; 9(9): 2627-2634, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39291207

RESUMO

Introduction: Peritoneal dialysis (PD) shows promise for urgent-start dialysis in end-stage renal disease (ESRD), with automated PD (APD) having advantages. However, there is limited multicenter randomized controlled trial (RCT) evidence comparing APD with temporary hemodialysis (HD) for this indication in China. Methods: This multicenter RCT enrolled 116 patients with ESRD requiring urgent dialysis from 11 hospitals, randomized to APD or HD. Patients underwent a 2-week treatment with APD or HD via a temporary central venous catheter (CVC), followed by a maintenance PD. Outcomes were assessed over 12 months during 8 visits. The primary outcome was dialysis-related complications. Results: The 1-year incidence of dialysis-related complications was significantly lower in the APD group than in the HD group (25.9% vs. 56.9%, P = 0.001). No significant differences were found between the groups in terms of PD catheter survival rates (P = 0.388), peritonitis-free survival rates (P = 0.335), and patient survival rates (P = 0.329). In terms of health economics, the total direct medical cost of the initial hospitalization for patients with ESRD was significantly lower in the APD group (27,008.39 CNY) than in the HD group (42,597.54 CNY) (P = 0.001), whereas the duration of the first hospital stay showed no significant difference (P = 0.424). Conclusion: For patients with ESRD needing urgent initiation of dialysis, APD was associated with a lower incidence of dialysis-related complications and lower initial hospitalization costs compared with HD, with no significant differences in PD catheter survival rate, peritonitis-free survival rates, or patient survival rates. These findings can guide clinical decision-making for the optimal dialysis modality for patients requiring urgent dialysis initiation.

4.
Int J Biol Macromol ; 278(Pt 2): 134568, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116980

RESUMO

Acinetobacter baumannii is currently one of the most important opportunistic pathogens causing severe nosocomial infections worldwide. Quorum Sensing (QS) system is a widespread mechanism in bacteria to coordinate group behavior by sensing the density of bacterial populations and affect eukaryotic host cell. In Acinetobacter baumannii, AbaI protein is used as QS molecule synthetase to synthesize N- acyl homoserine lactones (AHLs). Currently, QS has made great progress in the study of drug resistance, but there is still a lack of complete understanding of its damage to host cells after adhesion and invasion. Thus, in this study, we examined the effects of abaI mutant (ΔabaI) on the functions of adhesion and invasion, cell viability, inflammation, apoptosis in A. baumannii infected A549 cells, to evaluate the effects of ΔabaI in a zebrafish model. We found the group infected with ΔabaI increased cell viability, reduced adhesion and invasion, cell injury, inflammatory cytokine production and apoptosis. By RNA-Seq, we explored the possibility that abaI stimulated A549 cells inflammation by A. baumannii infection via TLR4/MAPK signaling pathway. In addition, the ΔabaI significantly reduced pathogenicity and recruitment to neutrophils in zebrafish. These observations suggest that abaI plays a major role in A. baumannii infection.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Inflamação , Percepção de Quorum , Peixe-Zebra , Animais , Peixe-Zebra/microbiologia , Acinetobacter baumannii/patogenicidade , Humanos , Infecções por Acinetobacter/microbiologia , Células A549 , Modelos Animais de Doenças , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Ligases/metabolismo , Ligases/genética
5.
Clin Ther ; 46(9): 702-710, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39112102

RESUMO

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.


Assuntos
Hiperpotassemia , Silicatos , Humanos , Hiperpotassemia/tratamento farmacológico , Silicatos/efeitos adversos , Silicatos/uso terapêutico , Silicatos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , China , Idoso , Adulto , Resultado do Tratamento , Potássio/sangue
6.
Ren Fail ; 46(2): 2380037, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39082686

RESUMO

INTRODUCTION: Our objective was to examine the factors associated with the serum angiopoietin-2/angiopoietin-1 (Angpt-2/Angpt-1) ratio in peritoneal dialysis (PD) patients and to investigate the association between Angpt-2/Angpt-1 ratio and cardiovascular and all-cause mortality. METHODS: Patients on PD who were prevalent between January 2014 and April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters, serum angiopoietin-2 and angiopoietin-1 levels. Patients were dichotomized into two groups according to a median of Angpt-2/Angpt-1 ratio and followed up prospectively until the end of the study. RESULTS: A total of 325 patients were enrolled, including 168 males (51.7%) with a mean age of 56.9 ± 14.2 years and a median PD duration of 32.4 (9.8-55.9) months. Multiple linear regression showed pulse pressure (ß = 0.206, p < .001) and high-sensitivity C-reactive protein (hs-CRP) (ß = 0.149, p = .011) were positively correlated with serum Angpt-2/Angpt-1 ratio, while residual renal function (RRF) (ß= -0.219, p < .001) was negatively correlated with serum Angpt-2/Angpt-1 ratio. Multivariate Cox regression analysis showed the high serum Angpt-2/Angpt-1 ratio was an independent predictor of cardiovascular mortality (hazard ratio (HR)=2.467, 95% confidence interval (CI) 1.243-4.895, p = .010) and all-cause mortality (HR = 1.486, 95%CI 1.038-2.127, p = .031). In further subgroup analysis by gender, a significant association was shown in high Angpt-2/Angpt-1 ratio with all-cause mortality in male (p < .05), but not in female patients (p>.05). CONCLUSIONS: High Angpt-2/Angpt-1 ratio is an independent risk factor for cardiovascular and all-cause mortality in PD patients.


Assuntos
Angiopoietina-1 , Angiopoietina-2 , Doenças Cardiovasculares , Diálise Peritoneal , Humanos , Masculino , Angiopoietina-2/sangue , Feminino , Pessoa de Meia-Idade , Diálise Peritoneal/mortalidade , Estudos Prospectivos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Idoso , Angiopoietina-1/sangue , Adulto , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Proteína C-Reativa/análise , Biomarcadores/sangue , Causas de Morte , Fatores de Risco , Modelos de Riscos Proporcionais
7.
J Cell Mol Med ; 28(10): e18381, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38780509

RESUMO

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.


Assuntos
Ácidos Aminossalicílicos , Fibroblastos , Fibrose Peritoneal , Fenótipo , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Ácidos Aminossalicílicos/farmacologia , Benzenossulfonatos/farmacologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/tratamento farmacológico , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Peritônio/patologia , Peritônio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo
8.
Free Radic Biol Med ; 218: 120-131, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583680

RESUMO

Sepsis-induced acute kidney injury (S-AKI) is the most common type of acute kidney injury (AKI), accompanied by elevated morbidity and mortality rates. This study investigated the mechanism by which lipid droplets (LDs) degraded via autophagy (lipophagy)required for RAB7 regulated ferroptosis in the pathogenesis of S-AKI. Here, we constructed the S-AKI model in vitro and in vivo to elucidate the potential relationship of lipophagy and ferroptosis, and we first confirmed that the activation of lipophagy promoted renal tubular epithelial cell ferroptosis and renal damage in S-AKI. The results showed that lipopolysaccharide (LPS) induced a marked increase in lipid peroxidation and ferroptosis, which were rescued by ferrstain-1 (Fer-1), an inhibitor of ferroptosis. In addition, LPS induced the remarkable activation of RAB7-mediated lipophagy. Importantly, silencing RAB7 alleviated LPS-induced lipid peroxidation and ferroptosis. Thus, the present study demonstrated the potential significant role of ferroptosis and lipophagy in sepsis-induced AKI, and contributed to better understanding of the pathogenesis and treatment targets of AKI.


Assuntos
Injúria Renal Aguda , Autofagia , Ferroptose , Peroxidação de Lipídeos , Lipopolissacarídeos , Sepse , Proteínas rab de Ligação ao GTP , proteínas de unión al GTP Rab7 , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/etiologia , Sepse/complicações , Sepse/metabolismo , Sepse/patologia , Sepse/genética , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Ferroptose/genética , Animais , Camundongos , Humanos , Masculino , Gotículas Lipídicas/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
9.
Front Med (Lausanne) ; 11: 1342344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449887

RESUMO

Background: Whether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients. Methods: This was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan-Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality. Results: A total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan-Meier curve showed the sarcopenic obesity (log-rank = 13.527, p < 0.001) group had significant lower survival rate compared to the nonsarcopenic non-obesity group. For multivariate analysis, the CICR method showed patients with sarcopenic obesity had significantly higher mortality rate (HR: 2.190, 95% CI: 1.011-4.743, p = 0.047) compared to those with nonsarcopenic non-obesity. Conclusion: Sarcopenia is not uncommon in PD patients, with a considerable proportion having sarcopenic obesity. There is a significant association between sarcopenic obesity and an increased risk of mortality in PD patients.

10.
Cell Biochem Funct ; 42(2): e3943, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379015

RESUMO

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus , Nefropatias Diabéticas , Glucosídeos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Sequenciamento de Cromatina por Imunoprecipitação , RNA-Seq , Cromatina , RNA Mensageiro/metabolismo
11.
Kidney Int Rep ; 9(2): 401-409, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344711

RESUMO

Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown. Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed. Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection. Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.

12.
Cell Death Dis ; 15(1): 63, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233375

RESUMO

Acute kidney injury (AKI) constitutes a prevalent clinical syndrome characterized by elevated morbidity and mortality rates, emerging as a significant public health issue. This study investigates the interplay between endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and ER-associated degradation (ER-phagy) in the pathogenesis of AKI. We employed four distinct murine models of AKI-induced by contrast media, ischemia-reperfusion injury, cisplatin, and folic acid-to elucidate the relationship between ER-phagy, ER stress, and apoptosis. Our findings reveal a marked decrease in ER-phagy coinciding with an accumulation of damaged ER, elevated ER stress, and increased apoptosis across all AKI models. Importantly, overexpression of DDRGK1 in HK-2 cells enhanced ER-phagy levels, ameliorating contrast-induced ER stress and apoptosis. These findings unveil a novel protective mechanism in AKI, wherein DDRGK1-UFL1-mediated ER-phagy mitigates ER stress and apoptosis in renal tubular epithelial cells. Our results thereby contribute to understanding the molecular underpinnings of AKI and offer potential therapeutic targets for its treatment.


Assuntos
Injúria Renal Aguda , Retículo Endoplasmático , Animais , Humanos , Camundongos , Injúria Renal Aguda/metabolismo , Apoptose , Autofagia/fisiologia , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia
13.
Ren Fail ; 46(1): 2290922, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38234178

RESUMO

Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929-0.986), white blood cells (OR 0.900, 95% CI: 0.844-0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755-0.993), body mass index (OR 0.860, 95% CI: 0.828-0.892), males (OR 0.708, 95% CI: 0.625-0.801), and albumin (OR 0.512, 95% CI: 0.389-0.673) had a negative association with high ERI baseline (all p < 0.05). There were 176 (13.9%) deaths in total including 89 cardiac/vascular deaths during follow-up. Cox regression analysis showed that ERI was positively associated with all-cause mortality, especially in some subgroups. ERI was associated with increased all-cause mortality in MHD patients, indicating the possibility of death prediction by ERI. Patients with high ERI warrant more attention.


Assuntos
Anemia , Eritropoetina , Hematínicos , Falência Renal Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anemia/etiologia , Epoetina alfa , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Idoso
14.
Kidney Int Rep ; 8(11): 2294-2306, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38025238

RESUMO

Introduction: Evocalcet is an oral calcimimetic agent with proven efficacy and safety in treating secondary hyperparathyroidism (SHPT) in Japanese patients on dialysis. Methods: This randomized, double-blind, intrapatient dose-adjustment, parallel-group, international multicenter study compared the efficacy and safety of evocalcet versus cinacalcet for 52 weeks in East Asian hemodialysis patients with SHPT. Results: In total, 203 and 200 patients were randomized to receive evocalcet or cinacalcet, respectively (overall, 70.1% had baseline intact parathyroid hormone (PTH) levels ≥500 pg/ml, with no between-group difference). Mean percentage changes in intact PTH levels from baseline were -34.7% and -30.2% in the evocalcet and cinacalcet groups at 52 weeks (between-group difference -4.4%, 95% confidence interval [CI] -13.1%, 4.3%, below the predefined 15% noninferiority margin). Overall, 67.3% and 58.7% of patients in the evocalcet and cinacalcet groups, respectively, achieved ≥30% decrease in intact PTH levels from baseline (between-group difference 8.6%; 95% CI -1.8%, 19.1%). No major safety concerns were observed. Gastrointestinal adverse events (AEs) were significantly less frequent with evocalcet compared with cinacalcet (33.5% vs. 50.5%, P = 0.001), whereas the incidence of hypocalcemia did not differ. Conclusion: Evocalcet might be a better alternative to cinacalcet for East Asian patients on hemodialysis with SHPT.

15.
Kidney Dis (Basel) ; 9(4): 306-316, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37900002

RESUMO

Introduction: Congestive heart failure (CHF) is one of the common complications in patients with end-stage kidney disease. In the general population, CHF increases the risk of the death. However, there is no well-designed relevant study in the Chinese hemodialysis (HD) population addressing the risks associated with CHF. The aim of this study was to explore the impact of CHF on clinical outcomes in HD patients. Methods: Data from a prospective cohort study, the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 (2012-2015), were analyzed. Demographic data, comorbidities, lab data, and death records were extracted. CHF was defined by the diagnosis records upon study inclusion. Our primary outcome was all-cause and cardiovascular (CV) mortality; secondary outcomes were all-cause and cause-specific hospitalization risk. Associations between CHF and outcomes were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were carried out. Results: Of 1,411 patients without missing CHF history information, 24.1% (340) had CHF diagnosis at enrollment. The overall mortality rates were 21.8% versus 12.0% (p < 0.001) in patients with and without CHF during follow-up, respectively. CHF was associated with higher all-cause mortality (adjusted HR: 1.72, 95% confidence interval [CI]: 1.17-2.53, p = 0.006), and the association with CV death was of similar magnitude (HR: 1.60, 95% CI: 0.91-2.81, p = 0.105). CHF patients had more episodes of hospitalization due to heart failure (HR: 2.93, 95% CI: 1.49-5.76, p < 0.01). However, compared with patients without CHF, the all-cause hospitalization risk was not much higher in CHF patients (HR: 1.09, 95% CI: 0.90-1.33, p = 0.39). Subgroup analysis found that the effect of CHF on all-cause mortality was stronger for male patients, patients with residual renal function, the elderly (≥60 years of age), patients with arteriovenous fistulae vascular accesses, nondiabetic patients, low-flux dialyzer users, and inadequately dialyzed patients (standardized Kt/V <2). Conclusion: In HD patients, CHF was found to be associated with a higher risk of all-cause mortality and cause-specific hospitalization risk. Further research is needed to identify opportunities to improve care for HD patients combined with CHF.

16.
Ren Fail ; 45(2): 2257808, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724537

RESUMO

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Estudos de Coortes , Cuidados Críticos , Unidades de Terapia Intensiva , Área Sob a Curva
17.
Int J Cardiol ; 391: 131334, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37696365

RESUMO

PURPOSE: To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population. METHODS: The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE. RESULTS: LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients. CONCLUSIONS: LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.

18.
Front Physiol ; 14: 1172308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576347

RESUMO

Background: Seasonal variation has an impact on plants, wild animals, and also human beings. Data have shown seasonal variation has a significant impact on patients' fluid status, biochemistry results, and outcomes in hemodialysis populations. The relevant data on peritoneal dialysis is scant. Methods: This was a cross sectional study. All patients followed up in our center had a peritoneal equilibration test and PD adequacy test every 6 months. All the peritoneal equilibration test and PD adequacy test data were collected during December 2019 to November 2020. The monthly delivery information of the whole center was collected from 2015 to 2019. Results: There were 366 patients and 604 sets of peritoneal equilibration test and PD adequacy test results in the study. Plasma albumin and phosphate levels were higher in summer. The monthly average outdoor temperature was positively correlated with plasma albumin. There was no seasonal difference in peritoneal dialysis ultrafiltration or urine volume. The percentage of low glucose concentration (1.5%) usage was higher in summer and lower in winter. Conclusion: Plasma albumin and phosphate levels were higher in summer in PD patients. Weaker glucose peritoneal dialysis dialysate was more widely used in summer. Understanding the seasonal variation of peritoneal dialysis is helpful in individualized treatment.

19.
BMC Nephrol ; 24(1): 242, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596523

RESUMO

BACKGROUND: Extraglomerular immune complex deposition is rare and only a few membranous nephropathy cases with tubular basement membrane deposits have been reported following allogeneic hematopoietic stem cell transplantation. CASE PRESENTATION: We reported a 56-year-old man with increased serum creatinine after allogeneic hematopoietic stem cell transplantation who underwent a renal biopsy. Tubular interstitial nephritis was identified on light microscope. The unique histologic features were diffuse tubular basement membrane immune complex deposition detected by both immunofluorescence and electron microscopy, while the glomerular involvement was inconspicuous. The differential diagnosis from other forms of tubular basement membrane deposition is discussed. CONCLUSION: Diffuse granular tubular basement membrane immune complex deposition with minimal glomerular involvement is also a manifestation of renal complication in hematopoietic stem cell transplantation recipient. However, the exact mechanism and target antigen remains unknown.


Assuntos
Glomerulonefrite Membranosa , Transplante de Células-Tronco Hematopoéticas , Masculino , Humanos , Pessoa de Meia-Idade , Complexo Antígeno-Anticorpo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Rim , Diagnóstico Diferencial
20.
BMC Nephrol ; 24(1): 233, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559023

RESUMO

BACKGROUND: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. METHODS: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). RESULTS: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). CONCLUSIONS: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04799067.


Assuntos
Hiperpotassemia , Falência Renal Crônica , Adulto , Humanos , Diálise Renal/efeitos adversos , Hiperpotassemia/epidemiologia , Estudos Prospectivos , Prevalência , População do Leste Asiático , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Potássio , Soluções para Diálise
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