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BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients. METHODS: Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls. RESULTS: A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN. CONCLUSION: The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.
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Ferroptose , Nefrite Lúpica , Redes Neurais de Computação , Humanos , Ferroptose/genética , Ferroptose/imunologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/genética , Feminino , Masculino , Adulto , Aprendizado de Máquina , Prognóstico , Pessoa de Meia-IdadeRESUMO
Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.
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Introduction: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. Methods: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Results: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Conclusion: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.
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Background: The prognostic significance of beta(ß)-blocker therapy in patients at end-stage renal disease, specifically those receiving peritoneal dialysis (PD) and presenting with heart failure, remains inadequately elucidated due to limited research conducted thus far. Methods: A retrospective analysis was performed on a cohort comprising 608 patients receiving PD between September 2007 and March 2019, with a subsequent follow-up period extending until December 2020. Cox regression and propensity score matching weighted analysis was used to model adjusted hazard ratios for ß-blocker use with heart failure-related mortality. Competing risk analysis and subgroup analysis were carried out to further elucidate the correlation. Results: ß-blockers were prescribed for 56.1% of the peritoneal dialysis patients. Heart failure occurred in 43.4% of the total population and 15.5% of deaths were due to heart failure. The prescription of ß-blockers was associated with a 43% lower adjusted hazard ratio (HR) for heart failure death within the cohort (95% confidence interval [CI] = 0.36-0.89; P = 0.013). Even after accounting for competing risk events, patients in the group using ß-blockers demonstrated a significantly lower cumulative risk of heart failure-related mortality compared to those not using ß-blockers (P = 0.007). This protective effect of ß-blockers was also observed in subgroup analyses. Conversely, ß-blocker use had no statistically significant associations with all-cause mortality. Conclusion: The use of ß-blockers was associated with a reduced risk of heart failure-related mortality in the PD population. Future randomized clinical trials are warranted to confirm the beneficial effect of ß-blockers in the context of PD.
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INTRODUCTION: The study presented here aimed to establish a predictive model for heart failure (HF) and all-cause mortality in peritoneal dialysis (PD) patients with machine learning (ML) algorithm. METHODS: We retrospectively included 1006 patients who initiated PD from 2010 to 2016. XGBoost, random forest (RF), and AdaBoost were used to train models for assessing risk for 1-year and 5-year HF hospitalization and mortality. The performance was validated using fivefold cross-validation. The optimal ML algorithm was used to construct the models to predictive the risk of the HF and all-cause mortality. The prediction performance of ML methods and Cox regression was compared. RESULTS: Over a median follow-up of 49 months. Two hundred and ninety-eight patients developed HF required hospitalization; 199 patients died during the follow-up. The RF model (AUC = 0.853) was the best performing model for predicting HF, and the XGBoost model (AUC = 0.871) was the best model for predicting mortality. Baseline moderate or severe renal disease, systolic blood pressure (SBP), body mass index (BMI), age, Charlson Comorbidity Index (CCI) score were strongly associated with HF hospitalization, whereas age, CCI score, creatinine, age, high-density lipoprotein cholesterol (HDL-C), total cholesterol, baseline estimated glomerular filtration rate (eGFR) were the most significant predictors of mortality. For all the above endpoints, the ML models demonstrated better discrimination than Cox regression. CONCLUSIONS: We developed and validated a novel method to predict the risk factors of HF and all-cause mortality that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among PD patients.
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Insuficiência Cardíaca , Diálise Peritoneal , Humanos , Nomogramas , Estudos Retrospectivos , Medição de Risco/métodos , Hospitalização , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Diálise Peritoneal/efeitos adversos , Aprendizado de Máquina , ColesterolRESUMO
OBJECTIVE: This study aimed to investigate the possible role of granulin (GRN) in activating the TLR9-IFN-α pathway in renal tubular epithelial cells (RTECs) and explore clues that RTECs regulate the micro-environment of inflammatory response in lupus nephritis (LN). METHODS: Renal sections from 57 LN patients and 30 non-LN patients were sampled for histological study, and GRN overexpression RTECs were applied for cytological study. RESULTS: In the histological study, GRN is highly expressed in LN RTECs with tubulointerstitial inflammation (TII) and well co-localized with TLR9. ROC analysis suggested a potential relationship between GRN expression in RTECs and therapeutic response. Moreover, IFN-α also highly expressed in LN RTECs with TII, and the intensity of IFN-α is positively correlated with the co-localization intensity of GRN and TLR9. In the cytological study, LN serum, especially serum from LN with TII, activates the expression of TLR9 in RTECs, and GRN engages the interaction of TLR9 to activate the expression of IFN-α in RTECs. While TLR9 inhibitors can suppress the expression of IFN-α in RTECs, the degree of inhibition is dose-dependent. CONCLUSION: The expression of GRN in RTECs is associated with interstitial inflammation and therapeutic response. GRN may mediate the activation of the TLR9-IFN-α pathway in RTECs and involve in the micro-environment of inflammatory response in LN.
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Granulinas , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Granulinas/metabolismo , Inflamação/metabolismo , Interferon-alfa/metabolismo , Rim/patologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/patologia , Receptor Toll-Like 9/metabolismoRESUMO
OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.
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Nefrologia , Humanos , Reprodutibilidade dos Testes , Qualidade de Vida/psicologia , Inquéritos e Questionários , Diálise Renal , Fadiga/terapia , China , Psicometria , TraduçõesRESUMO
Posterior reversible encephalopathy syndrome (PRES) is a rare clinical disease, which has been seen in patients with systemic lupus erythematosus (SLE). Its main manifestations are seizure, headache and other neurological symptoms. While the condition is reversible, if not treated in time, there can be risks of cerebral haemorrhage. We report here the case of a young patient with SLE who developed PRES after receiving the immunosuppressant, mycophenolate mofetil. Neurological symptoms, signs, or changes in a patient's condition that cannot be explained by lupus, should alert physicians to the possibility of the drug causing PRES, and prompt discontinuation should ensue.
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Lúpus Eritematoso Sistêmico , Síndrome da Leucoencefalopatia Posterior , Humanos , Ácido Micofenólico/efeitos adversos , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Lúpus Eritematoso Sistêmico/complicações , Convulsões/etiologia , CefaleiaRESUMO
Objective: This study was conducted to understand the influencing factors for home peritoneal dialysis patients choosing APD and to provide a scientific basis for improving the completion rate of APD treatment and the follow-up of peritoneal dialysis patients. Methods: The study was a cross-sectional questionnaire-based study. A total of 588 patients on peritoneal dialysis were randomly selected from 6 regions in Fujian Province in southern China using a stratified cluster sampling method. Results: The mean age of the patients were 56.5 ± 14.73 years. In the univariate analysis, knowledge, user experience and family support were the factors that affected patients' choice of APD (all P < 0.05) and were positively correlated with the treatment utilization rate. In the multivariate analysis, 3 factors (treatment with APD, knowledge of APD, and family support) remained significantly associated not choosing APD. The selection rate for APD was 2.594 times higher among patients who had received APD than among patients who had never received APD. The selection rate for patients with "a lot of knowledge" about APD was 10.75 times that of patients with "no knowledge". Conclusion: Patients' knowledge of APD, experience in application and family support were the main factors affecting the choice of APD as a treatment mode (P < 0.05) and were positively correlated with the treatment utilization rate. Further studies are needed to improve the APD treatment completion rates by modulation the above-mentioned factors. Relevance to Clinical Practice: This study provides scientific evidence for improving APD treatment completion rates and improving patient quality of life.
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Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/ß-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of "three more and one less," reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/ß-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.
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BACKGROUND: The aim was to study clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with vascular lesions. METHODS: We enrolled a Chinese cohort with 458 biopsy-confirmed primary IgAN patients for a retrospective analysis. They were divided into three groups according to vascular lesions: no vascular lesions (n = 239), arterio-/arteriolosclerosis (n = 181) and microangiopathic lesions (n = 38). The clinicopathological features and renal outcome were recorded. In univariate and multivariate models, association between vascular lesions and renal outcome and vascular lesions associated clinical factors were analyzed. RESULTS: Patients with vascular lesions presented worse clinical characteristics with regard to blood pressure and kidney function, and segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2) and lymphocytes and monocytes infiltration were more common. Furthermore, older age, hyperuricemia, proteinuria, global glomerulosclerosis and endocapillary hypercellularity (E1) were more severe in patients with simple arterio-/arteriolosclerosis. By multivariate logistic regression, age, MAP and eGFR were significantly associated with vascular lesions. Vascular lesions, especially arterio-/arteriolosclerosis, were significantly associated with poorer renal survival in IgAN patients, and renal survival was similar whether patients with arterio-/arteriolosclerosis received immunosuppressive therapy. In addition to eGFR, arterio-/arteriolosclerosis, along with arterial intimal fibrosis, was an independent predictor for renal survival in multivariate Cox analyses. CONCLUSION: IgAN patients with vascular lesions, especially with arterio-/arteriolosclerosis, presented more severe clinicopathological features. Renal function, blood pressure and age contributed to distinguishing patients with vascular lesions. Arterio-/arteriolosclerosis lesions were associated with poorer renal survival.
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Arteriolosclerose , Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/complicações , Prognóstico , Estudos Retrospectivos , Arteriolosclerose/complicações , Arteriolosclerose/patologia , Rim , Fatores de Risco , Fibrose , Taxa de Filtração GlomerularRESUMO
OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.
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Hiperparatireoidismo Secundário , Complicações Pós-Operatórias , Ablação por Radiofrequência , Insuficiência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Hipocalcemia/epidemiologia , Fósforo , Ablação por Radiofrequência/efeitos adversos , Traumatismos do Nervo Laríngeo Recorrente/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Terapia de Substituição Renal , Distribuição por IdadeRESUMO
BACKGROUND: Peritoneal catheter related infection is one of the main complications and the major cause of technical failure of peritoneal dialysis (PD) treatment. However, PD catheter tunnel infection can be difficult to diagnosis and resolve. We presented a rare case in which a granuloma formation after repeated episodes of peritoneal dialysis catheter-related infection. CASE PRESENTATION: A 53-year-old female patient with kidney failure due to chronic glomerulonephritis treated with peritoneal dialysis for 7 years. The patient had repeated exit-site and tunnel inflammation, and repeated suboptimal courses of antibiotics. She switched to hemodialysis after 6 years in a local hospital without the peritoneal dialysis catheter being removed. The patient complained of an abdominal wall mass that lasted for several months. She was admitted to the Department of surgery to undergo mass resection. The resected tissue of the abdominal wall mass was sent for pathological examination. The result showed foreign body granuloma with necrosis and abscess formation. After the surgery, the infection did not recur. CONCLUSIONS: The following key points can be learned from this case: 1. It is important to strengthen patient follow-up. 2.The PD catheter should be removed as early as possible in patients who do not need long-term PD, especially in patients with a history of exit-site and tunnel infections. 3. For patients presenting abnormal subcutaneous mass, attention should be paid to the possibility of the granuloma formation of infected Dacron cuffs of the PD catheter. If catheter infection occurs repeatedly, catheter removal and debridement should be considered.
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Infecções Relacionadas a Cateter , Diálise Peritoneal , Peritonite , Feminino , Humanos , Pessoa de Meia-Idade , Infecções Relacionadas a Cateter/etiologia , Cateterismo/efeitos adversos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Cateteres de Demora/efeitos adversos , Granuloma/etiologia , Peritonite/etiologiaRESUMO
Objective: Patient empowerment can be achieved through the PBL model. The purpose of the present study was to evaluate the effectiveness and feasibility of patient empowerment through the PBL model in health continuing education of peritoneal dialysis (PD) patients. Methods: From March 2017 to April 2017, a total of 94 participants were randomly assigned to the PBL group and the traditional group, with 47 patients in each group. Patients of the PBL group were divided into 5 study groups; and six PBL health education activities were held. The basic knowledge, self-management behavior, quality of life, anxiety, and depression were assessed among the traditional group and the PBL group. The average follow-up duration was 10.6±1.5 months. Results: Compared with patients in the traditional group, patients in the PBL group had higher scores of basic knowledges for PD (84.33±3.55 vs 91.19±3.07; P<0.001), higher scores of self-management (61.19±3.71 vs 71.47±2.89; P< 0.001), better scores of quality of life (85.99±14.33 vs 102.64±9.43; P < 0.001), and better scores of satisfaction (90.78±1.32 vs 98.21±1.25; P < 0.001). Furthermore, the scores of anxieties (52.39±4.55 vs 46.46±4.63; P < 0.001) and the scores of depressions were lower (49.95±6.76 vs 45.80±8.77; P =0.01) in patients who participated in the PBL mode of education than in the traditional educational group. Conclusion: The empowerment model of PBL health education can effectively improve the knowledge, skills and quality of life of PD patients. Relevance to Clinical Practice: The findings identified in this study will help to improve the quality of nursing care and health education for PD patients. Patient or Public Contribution: The study design involved patients on PD training. The knowledge and skills of PD and quality of life will improve after they participate the PBL health education activities.
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Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Peritonite , Humanos , Diálise Peritoneal/efeitos adversos , Abscesso/diagnóstico , Abscesso/etiologia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/diagnóstico , Peritonite/tratamento farmacológico , Peritonite/etiologiaRESUMO
Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin-angiotensin-aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin-angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.
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Methylation is one of the most extensive modifications of biological macromolecules and affects cell-fate determination, development, aging, and cancer. Several methylation modifications, including 5-methylcytosine and N6-methyladenosine, play an essential role in many cancers. However, little is known about the relationship between methylation and the prognosis of clear cell renal cell carcinoma (ccRCC). Here, we established a methylation-regulating genes prognostic signature (MRGPS) to predict the prognoses of ccRCC patients. We obtained ccRCC samples from The Cancer Genome Atlas and identified methylation-regulatingd genes (MRGs) from the Gene Set Enrichment Analysis database. We also determined differentially expressed genes (DEGs) and performed cluster analysis to identify candidate genes. Subsequently, we established and validated an MRGPS to predict the overall survival of ccRCC patients. This was also verified in 15 ccRCC samples collected from the Fujian Provincial Hospital via quantitative real-time transcription (qRT-PCR). While 95 MRGs were differentially expressed (DEGs1) between tumor and normal tissues, 17 MRGs were differentially expressed (DEGs2) between cluster 1 and 2. Notably, 13 genes common among DEGs1 and DEGs2 were identified as hub genes. In fact, we established three genes (NOP2, NSUN6, and TET2) to be an MRGPS based on their multivariate Cox regression analysis coefficients (p < 0.05). A receiver operating characteristic curve analysis confirmed this MRGPS to have a good prognostic performance. Moreover, the MRGPS was associated with characteristics of the tumor immune microenvironment and responses to inhibitor checkpoint inhibitors. Data from "IMvigor 210" demonstrated that patients with a low MRGPS would benefit more from atelozumab (p < 0.05). Furthermore, a multivariate analysis revealed that MRGPS was an independent risk factor associated with ccRCC prognosis (p < 0.05). Notably, a nomogram constructed by combining with clinical characteristics (age, grade, stage, and MRGPS risk score) to predict the overall survival of a ccRCC patient had a favorable predictive value. Eventually, our qRT-PCR results showed that tumor tissues had higher NOP2 and NSUN6 expression levels and lower TET2 expression than normal tissues of ccRCC samples. While the proposed MRGPS comprising NOP2, NSUN6, and TET2 can be an alternative prognostic biomarker for ccRCC patients, it is a promising index for personalized ICI treatments against ccRCC.
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BACKGROUND/AIMS: The aim of the study was to investigate the clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with crescents. METHODS: Four hundred and fifty-eight biopsy-proven primary IgAN patients included between January 2010 and October 2021 for a retrospective analysis were divided into three groups according to crescent score of the updated Oxford classification: C0 group (n = 255), C1 group (n = 187) and C2 group (n = 16). The clinicopathological features and renal outcomes were recorded. In univariate and multivariate models, the association between crescents and renal outcome and C2-associated clinical factors were analyzed. RESULTS: Patients with a higher proportion of crescents presented worse clinical characteristics with regard to kidney function, proteinuria, hematuria, hemoglobin, uric acid, cholesterol, and serum albumin, while global glomerulosclerosis, segmental adhesion, tuft necrosis, segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2), and lymphocyte and monocyte infiltration were more severe. By multivariate logistic regression analysis, eGFR (OR 0.981, 95% CI 0.964-0.999, P = 0.039), proteinuria (OR 1.655, 95% CI 1.180-2.321, P = 0.004), and hematuria (OR 4.752, 95% CI 1.426-15.835, P = 0.011) were significantly associated with C2. C2 was significantly associated with poorer renal survival even in patients receiving immunosuppressive therapy. Nevertheless, only eGFR at baseline, rather than crescents, was an independent predictor for renal survival in multivariate Cox analyses. CONCLUSION: IgAN patients with crescents presented more severe clinical and pathological features. Renal function, proteinuria and hematuria contributed to identifying patients with crescents. Crescents were associated with poorer renal survival, even in patients receiving immunosuppressive therapy, but it was not an independent predictor.
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Glomerulonefrite por IGA , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Hematúria/etiologia , Humanos , Rim , Masculino , Proteinúria/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: To evaluate clinical application value of radiofrequency ablation (RFA) in refractory hyperparathyroidism secondary to chronic kidney disease (CKD) by comparing the safety and effectiveness of RFA with parathyroidectomy with autotransplantation (PTX + AT). METHODS: A retrospective study was conducted on 80 patients with CKD with refractory hyperparathyroidism who underwent RFA or PTX + AT between January 2018 and February 2021. Serum parathyroid hormone (PTH), calcium, and phosphorus levels, complications, clinical symptoms, visual analogue scale (VAS) scores, hospital stay duration, and postoperative recurrence rate were compared between the 2 groups. RESULTS: Serum PTH, phosphorous, and calcium levels and the VAS scores improved significantly after RFA and PTX + AT (P < 0.05). Significant differences were observed between the 2 groups in postoperative (day 1 and week 1) levels of serum PTH and postoperative day 1 of serum calcium and phosphorus levels (P < 0.05), with more pronounced reduction after PTX + AT. Although the incidence of recurrent laryngeal nerve (RLN) injury was slightly higher in the RFA group compared with the PTX + AT group (26.67% vs. 16.67%; P > 0.05), RFA markedly decreased the risk of severe hypocalcemia (SH) (20% vs. 46.67%; P < 0.05) and shortened hospital stay (7.53 ± 2.67 days vs. 12.13 ± 3.86 days; P < 0.05). The 6-month recurrence rate was 23.3% (7 of 30) in the RFA group and 30% (9 of 30) in the PTX + AT group (P > 0.05). CONCLUSION: RFA can treat refractory secondary hyperparathyroidism (SHPT) with similar clinical efficacy as surgery and achieve faster recovery and a lower incidence of postoperative SH.
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Few studies have investigated the relationship between sarcopenia and mild to moderate renal decline. This study aimed to investigate the relationship between chronic kidney disease (CKD) and sarcopenia. In total, 123 patients hospitalized with CKD and 57 healthy volunteers who underwent physical examination during the same period (control group) were analyzed. Body compositions were measured by dual-energy X-ray absorptiometry, and the relative appendicular skeletal muscle index (RASMI) was calculated. Muscular strength was evaluated using hydraulic hand dynamometer. Walking speed within 6 m was measured for muscular function assessment. Single-photon emission computed tomography was performed to measure the glomerular filtration rate of CKD patients, who were then divided into CKD1 (55 patients in CKD stages 1 and 2) and CKD2 (68 patients in CKD stages 3-5). RASMI showed a downward trend with CKD progression (P = 0.001). Multivariate logistic regression analysis showed that age and CKD progression were independent risk factors for sarcopenia. The morbidity of sarcopenia was significantly greater in CKD patients than in healthy volunteers, and the degree of muscle loss was closely related to CKD progression.