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The transcription factor Twist1 plays a vital role in normal development in many tissue systems and continues to be important throughout life. However, inappropriate Twist1 activity has been associated with kidney injury and fibrosis, though the underlying mechanisms involved remain incomplete. Here, we explored the role of Twist1 in regulating fibroblast behaviors and the development kidney fibrosis. Initially Twist1 protein and activity was found to be markedly increased within interstitial myofibroblasts in fibrotic kidneys in both humans and rodents. Treatment of rat kidney interstitial fibroblasts with transforming growth factor-ß1 (a profibrotic factor) also induced Twist1 expression in vitro. Gain- and loss-of-function experiments supported that Twist1 signaling was responsible for transforming growth factor-ß1-induced fibroblast activation and fetal bovine serum-induced fibroblast proliferation. Mechanistically, Twist1 protein promoted kidney fibroblast activation by driving the expression of downstream signaling proteins, Prrx1 and TNC. Twist1 directly enhanced binding to the promoter of Prrx1 but not TNC, whereas the promoter of TNC was directly bound by Prrx1. Finally, mice with fibroblast-specific deletion of Twist1 exhibited less Prrx1 and TNC protein abundance, interstitial extracellular matrix deposition and kidney inflammation in both the unilateral ureteral obstruction and ischemic-reperfusion injury-induced kidney fibrotic models. Inhibition of Twist1 signaling with Harmine, a ß-carboline alkaloid, improved extracellular matrix deposition in both injury models. Thus, our results suggest that Twist1 signaling promotes the activation and proliferation of kidney fibroblasts, contributing to the development of interstitial fibrosis, offering a potential therapeutic target for chronic kidney disease.
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OBJECTIVE: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. RESULTS: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) µmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 µmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. CONCLUSIONS: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.
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Anticuerpos Anticitoplasma de Neutrófilos , Autoanticuerpos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Anciano , Estudios Retrospectivos , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Glomerulonefritis/inmunología , Glomerulonefritis/mortalidad , Glomerulonefritis/terapia , Glomerulonefritis/diagnóstico , Glomerulonefritis/sangre , Estudios de Seguimiento , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangreRESUMEN
BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. METHODS: 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. RESULTS: In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. CONCLUSIONS: FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.
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Biomarcadores , Fibrinógeno , Glomerulonefritis Membranosa , Síndrome Nefrótico , Receptores de Fosfolipasa A2 , Humanos , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Receptores de Fosfolipasa A2/inmunología , Síndrome Nefrótico/sangre , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/complicaciones , Adulto , Biomarcadores/sangre , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Curva ROC , Estudios Retrospectivos , Inducción de Remisión , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Factores de RiesgoRESUMEN
Background: High sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear. Aims: The study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD. Methods: In all, 409 patients with CKD stages 1-4 (G1-G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman's correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression. Results: Of the enrolled patients with CKD, the median urinary protein was 0.94 (0.28-3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52-110.99) mL/min/1.73 m2. The distributions of CKD stages G1-G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171-4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses. Conclusion: The combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD.
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BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.
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Neoplasias de la Mama , Supervivientes de Cáncer , Fatiga , Moxibustión , Humanos , Femenino , Moxibustión/métodos , Moxibustión/efectos adversos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Fatiga/etiología , Fatiga/terapia , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Calidad de Vida , China/epidemiología , Anciano , Rayos Infrarrojos/uso terapéuticoRESUMEN
Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.
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Lesión Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus reuteri/fisiología , Limosilactobacillus reuteri/metabolismo , Animales , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Ratones , Lipopolisacáridos/metabolismo , Masculino , Riñón/microbiología , Riñón/metabolismo , Heces/microbiología , Modelos Animales de Enfermedad , Creatinina/sangre , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacosRESUMEN
AIM: To evaluate the potential of the combined individual vascular histopathological lesion and serum 25-hydroxy vitamin D [25(OH)D] level as predictors of outcomes in patients with diabetes and chronic kidney disease. METHODS: A total of 190 patients with type 2 diabetes and kidney disease stages 1-4 were retrospectively included. Kaplan-Meier analysis and the log-rank test were performed to assess renal survival differences. And the time-dependent receiver operating characteristic analyses were used to characterize the predictive accuracy. Hazard ratios for vascular lesion scores and 25(OH)D levels with renal outcomes were estimated using Cox proportional hazards regression models with follow-up time. RESULTS: Over a median follow-up of 23.78 (12.61, 37.14) months, 71 patients (37.4 %) experienced the renal outcomes. Enrolled patients with more severe vascular lesions had worse kidney function, heavier proteinuria, lower serum 25(OH)D levels, and higher prevalence of composite kidney outcomes. Baseline serum 25(OH)D was a significant independent risk factor for vascular lesion scores. The effect of serum 25(OH)D level on kidney prognosis was more pronounced in males and those with more exacerbated vascular lesions (score 2). The severity of vascular lesions and serum 25(OH)D levels were associated with unfavorable kidney outcomes. Accordingly, further time-dependent receiver operating characteristic curves confirmed that combined 25(OH)D level and vascular lesion score had a stable and reliable performance in renal outcomes prediction at short and long-term follow-up times. CONCLUSIONS: 25(OH)D level and vascular lesion scores in kidney histopathology could serve as a useful risk-stratification tool for predicting renal progression in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Progresión de la Enfermedad , Vitamina D , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/sangre , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Vitamina D/sangre , Vitamina D/análogos & derivados , Pronóstico , Estudios de Seguimiento , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/sangre , Biomarcadores/sangre , Biomarcadores/análisis , Factores de Riesgo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Anciano , Tasa de Filtración Glomerular , Medición de Riesgo/métodosRESUMEN
Lipid accumulation is a factor contributing to the pathogenesis of acute kidney injury (AKI), yet there are currently no approved pharmacotherapies aside from adjuvant therapy. A developed reactive oxygen species (ROS)-responsive drug delivery system (NPSBG@Cur) was developed to deliver the autophagy activator curcumin (Cur) in order to alleviate AKI by activating autophagy and promoting lipid droplet degradation. The nanoparticles were shown to be ROS-responsive in the H2O2 medium and demonstrate ROS-responsive uptake in palmitate (PA)-induced oxidative stress-damaged cells. NPSBG@Cur was found to effectively inhibit lipid accumulation by autophagosome transport in kidney tubular cells. Additionally, in a mouse AKI model, NPSBG@Cur was observed to significantly ameliorate renal damage by activating autophagy flux and improving lipid transport. These results suggest that the ROS-responsive drug delivery system augmented the therapeutic effect of Cur on AKI by improving lipid metabolism through autophagy activation. Therefore, targeting lipid metabolism with NPSBG@Cur may be a promising AKI treatment strategy.
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Lesión Renal Aguda , Curcumina , Nanopartículas , Ratones , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/farmacología , Lesión Renal Aguda/tratamiento farmacológico , LípidosRESUMEN
BACKGROUNDS: Accumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). OBJECTIVES: We aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. METHODS: Total 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. RESULTS: All enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10-6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (ß = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (ß = -3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10-6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. CONCLUSIONS: ΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10-6 mm2/s and <66 × 10-6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/patología , Insuficiencia Renal Crónica/complicaciones , Riñón/patología , Fallo Renal Crónico/patología , Nefropatías Diabéticas/diagnóstico por imagen , Nefropatías Diabéticas/etiología , Tasa de Filtración Glomerular , Imagen por Resonancia MagnéticaRESUMEN
Importance: Despite the expansion of published electronic alerts for acute kidney injury (AKI), there are still concerns regarding their effect on the clinical outcomes of patients. Objective: To evaluate the effect of the AKI alert combined with a care bundle on the care and clinical outcomes of patients with hospital-acquired AKI. Design, Setting, and Participants: This single-center, double-blind, parallel-group randomized clinical trial was conducted in a tertiary teaching hospital in Nanjing, China, from August 1, 2019, to December 31, 2021. The inclusion criteria were inpatient adults aged 18 years or older with AKI, which was defined using the Kidney Disease: Improving Global Outcomes creatinine criteria. Participants were randomized 1:1 to either the alert group or the usual care group, which were stratified by medical vs surgical ward and by intensive care unit (ICU) vs non-ICU setting. Analyses were conducted on the modified intention-to-treat population. Interventions: A programmatic AKI alert system generated randomization automatically and sent messages to the mobile telephones of clinicians (alert group) or did not send messages (usual care group). A care bundle accompanied the AKI alert and consisted of general, nonindividualized, and nonmandatory AKI management measures. Main Outcomes and Measures: The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days after randomization. Secondary patient-centered outcomes included death, dialysis, AKI progression, and AKI recovery. Care-centered outcomes included diagnostic and therapeutic interventions for AKI. Results: A total of 2208 patients (median [IQR] age, 65 [54-72] years; 1560 males [70.7%]) were randomized to the alert group (n = 1123) or the usual care group (n = 1085) and analyzed. Within 7 days of randomization, median (IQR) maximum absolute changes in eGFR were 3.7 (-6.4 to 19.3) mL/min/1.73 m2 in the alert group and 2.9 (-9.2 to 16.9) mL/min/1.73 m2 in the usual care group (P = .24). This result was robust in all subgroups in an exploratory analysis. For care-centered outcomes, patients in the alert group had more intravenous fluids (927 [82.6%] vs 670 [61.8%]; P < .001), less exposure to nonsteroidal anti-inflammatory drugs (56 [5.0%] vs 119 [11.0%]; P < .001), and more AKI documentation at discharge (560 [49.9%] vs 296 [27.3%]; P < .001) than patients in the usual care group. No differences were observed in patient-centered secondary outcomes between the 2 groups. Conclusions and Relevance: Results of this randomized clinical trial showed that the electronic AKI alert did not improve kidney function or other patient-centered outcomes but changed patient care behaviors. The findings warrant the use of a combination of high-quality interventions and AKI alert in future clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03736304.
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Lesión Renal Aguda , Alarmas Clínicas , Diálisis Renal , Anciano , Humanos , Masculino , Lesión Renal Aguda/terapia , Lesión Renal Aguda/diagnóstico , Creatinina , Hospitales de Enseñanza , Unidades de Cuidados Intensivos , Femenino , Persona de Mediana EdadRESUMEN
Nocardiosis manifests as an opportunistic infection, primarily affecting individuals who are immunocompromised and susceptible to the infection. We present a case study of one patient with nephrotic syndrome and membranous nephropathy, who underwent treatment with prednisone and cyclosporine in 2016. In early 2017, the patient was diagnosed with a "fungal infection" and discontinued the use of cyclosporine. After one month of anti-infection therapy, a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region. The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses, multiple lung and brain lesions, and a positive culture of Nocardia in the drainage. We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and voriconazole. However, the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation. During the five-month follow-up period following the discharge, the patient displayed an enhanced nutritional status and stable renal function. The focal infection ultimately resolved during the subsequent three years. Neuro-infection caused by Nocardia should be considered in immunocompromised patients, and TMP-SMX is the preferred initial therapy; however, because of the high mortality rate, a long-term combination therapy with imipenem, cefotaxime, amikacin, and TMP-SMX is suggested.
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Objective: To explore the influence of case-based learning (CBL) teaching methods in comparison to the traditional lecture-based learning (LBL) model in clinical teaching of nephrology for master's degree students in clinical medicine. Methods: Clinical medicine master's degree students who were trained in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from December 2015 to December 2021 were selected as the study objects. The selected students were divided into two groups: the LBL group comprised 16 graduate students who received the traditional LBL model from December 2015 to December 2018, and the CBL group comprised 18 graduate students who received the CBL teaching methods from January 2019 to December 2021. Both groups participated in the professional theoretical knowledge assessment, including objective and subjective questions and calculating the total score), and the examination of clinical skills communication ability, preparation of handling materials, anesthesia techniques, operational skills, aseptic techniques, and postoperative management), at the time of discharge from the department. The independent learning ability (self-management ability, information ability, and learning ability) of students of the two groups after teaching was then assessed, and the satisfaction of the two groups with their respective teaching mode (including satisfaction with the teaching format, teaching effectiveness, interest stimulation, independent learning and the improvement of teamwork ability) was assessed by the questionnaire on the degree of satisfaction of the two groups. Results: The assessment scores of professional theoretical knowledge in the CBL group were significantly higher than those in the LBL group in objective questions, subjective questions, and total scores (P1 = .028; P2 = .036; P3 = .041). The CBL group scored higher than the LBL group in the assessment of communication skills, preparation of operative items, anesthesia technique, operative skills, aseptic technique, and postoperative handling skills, but the differences were not statistically significant (P1 = .071; P2 = .260; P3 = .184; P4 = .127; P5 = .352; P6 = .584). The self-management ability, information ability, and learning ability scores of students in the CBL group were significantly higher than those in the LBL group (P1 = .006; P2 = .013; P3 = .003). Students in the CBL group were significantly higher than those in the LBL group in terms of satisfaction with teaching form, teaching effect, interest stimulation, improvement of independent learning ability, and satisfaction with teamwork ability (P1 = .015; P2 = .008; P3 = .010; P4 = .024; P5 = .022). Conclusions: The CBL teaching model can improve and enhance the clinical thinking ability of clinical medicine master's degree students in nephrology, and stimulate their interest in learning. Professional master's degree students have a high degree of satisfaction with the CBL model.
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Medicina Clínica , Nefrología , Humanos , Aprendizaje Basado en Problemas/métodos , Estudiantes , Encuestas y CuestionariosRESUMEN
BACKGROUND: The main treatment method for end-stage renal disease (ESRD) is maintenance hemodialysis (MHD). With the continuous improvement of dialysis technology, the survival period of MHD patients has been effectively prolonged, but dialysis technology still cannot completely replace renal function. OBJECTIVE: To study the dietary compliance and its correlation with thirst in MHD patients and to provide guidance for clinical development of corresponding intervention countermeasures. METHODS: A total of 90 patients who received MHD treatment from March 2021 to March 2022 were selected as objects. The Renal Adherence Attitudes Questionnaire (RAAQ) and the Renal Adherence Behaviour Questionnaire (RABQ) were used to analyze the dietary compliance and thirst status of patients. Pearson correlation analysis was used to analyze the correlation between diet compliance and thirst. RESULTS: Positive correlations were found between VAS and DTI, SXI and TDS (P< 0.05). Social restrictive attitude was positively correlated with VAS, DTI, SXI, TDS, acceptance attitude and compliance in facing difficulties (P< 0.05), and negatively correlated with self-care compliance (r=-0.35, P< 0.05). Health attitude was positively correlated with VAS, DTI and SXI (P< 0.05). Acceptance attitude was positively correlated with DTI, SXI and TDS (P< 0.05). High RAAQ was associated with high VAS (b= 0.11, 95% CI: 0.05, 0.18), DTI (b= 0.28, 95% CI: 0.17, 0.38), SXI (b= 0.24, 95% CI: 0.14, 0.34) and TDS (b= 0.26, 95% CI: 0.13, 0.4). CONCLUSION: The overall performance of dietary compliance in patients with MHD is at a moderate level, and dietary compliance is negatively correlated with disease perception.
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PURPOSE: This study was developed to evaluate the effects of moxibustion on tumor microenvironmental hypoxia in a murine model of Lewis lung carcinoma (LLC). METHODS: Twenty-four tumor-bearing mice were randomized into tumor group (T), tumor + cisplatin group (TC), tumor + moxibustion group (TM), and tumor + cisplatin + moxibustion group (TMC) (n = 6/group). Six age-matched C57BL/6 mice were employed as control group (Ctrl). A tumor model was established by implanting LLC cells into the right flank of each mouse. Animals in the TM group received moxibustion treatment at the ST36 (bilateral) and GV4 acupoints on the day of visible tumor formation. Moxibustion treatment was performed every other day for a total of 7 sessions. Animals in the TC group were intraperitoneally injected with cisplatin (3 mg/kg) on day 3 after visible tumor formation, and this treatment was performed every 3 days for 4 times. Animals in the TMC group underwent combined moxibustion and chemotherapy treatment, following the same conditions as outlined above. Following treatment, the concentrations of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and Ki67 were measured using ELISA, Western blot, and immunohistochemical staining. RESULTS: Compared to the tumor group, treatment in the TM, TC, and TCM groups resulted in varying reductions in tumor growth (P < .001 or P < .05), while tumor microenvironmental hypoxia was alleviated as evidenced by the downregulation of HIF-1α, VEGFA, and CD31(P < .001-P < .05). CONCLUSION: Our results suggest that a combined approach of moxibustion and cisplatin can alleviate intratumoral hypoxia, promote vascular normalization, and slow the growth of LLC tumors in mice.
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Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Moxibustión , Ratones , Animales , Cisplatino/farmacología , Cisplatino/uso terapéutico , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Ratones Endogámicos C57BL , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Microambiente Tumoral , HipoxiaRESUMEN
BACKGROUND: Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes. CASE PRESENTATION: We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient's kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites. CONCLUSIONS: This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.
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Lesión Renal Aguda , Cistatina C , Humanos , Femenino , Anciano , Ascitis/diagnóstico , Ascitis/etiología , Creatinina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Diagnóstico ErróneoRESUMEN
SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney protection. The current murine experiments show that IL-1R1 activation in the proximal tubule exacerbates toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorates AKI by restoring VEGFA-dependent endothelial cell viability. Using this information, future delivery strategies can maximize the protective effects of blocking IL-1R1 while mitigating unwanted actions of IL-1R1 manipulation. BACKGROUND: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. IL-1R1 is expressed on some myeloid cell populations and on multiple kidney cell lineages, including tubular and endothelial cells. Pharmacological inhibition of the IL-1R1 does not consistently protect the kidney from injury, suggesting there may be complex, cell-specific effects of IL-1R1 stimulation in AKI. METHODS: To examine expression of IL-1 and IL-1R1 in intrinsic renal versus infiltrating immune cell populations during AKI, we analyzed single-cell RNA sequencing (scRNA-seq) data from kidney tissues of humans with AKI and mice with acute aristolochic acid exposure. We then investigated cell-specific contributions of renal IL-1R1 signaling to AKI using scRNA-seq, RNA microarray, and pharmacological interventions in mice with IL-1R1 deletion restricted to the proximal tubule or endothelium. RESULTS: scRNA-seq analyses demonstrated robust IL-1 expression in myeloid cell populations and low-level IL-1R1 expression in kidney parenchymal cells during toxin-induced AKI. Our genetic studies showed that IL-1R1 activation in the proximal tubule exacerbated toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorated aristolochic acid-induced AKI by restoring VEGFA-dependent endothelial cell viability and density. CONCLUSIONS: These data highlight opposing cell-specific effects of IL-1 receptor signaling on AKI after toxin exposure. Disrupting pathways activated by IL-1R1 in the tubule, while preserving those triggered by IL-1R1 activation on endothelial cells, may afford renoprotection exceeding that of global IL-1R1 inhibition while mitigating unwanted actions of IL-1R1 blockade.
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Lesión Renal Aguda , Receptores de Interleucina-1 , Humanos , Ratones , Animales , Receptores de Interleucina-1/genética , Apolipoproteínas M , Células Endoteliales/metabolismo , Lesión Renal Aguda/patología , Ratones Noqueados , Interleucina-1 , Endotelio/metabolismo , Ratones Endogámicos C57BLRESUMEN
The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P < 0.01). After behavioral testing, MSPS model rats had decreased activated c-Fos positive OXNs. Still, EA in SPS rats increased that number and elevated orexin type 1 receptors (OXR1) protein expression in the LH. Furthermore, after administering SB334867 (an OXR1 antagonist) to MSPS model rats, the effects of EA therapy on anxiety-like behaviors (ALBs) were significantly diminished. Additionally, when low-dose orexin-A (LORXA) was administered intracerebroventricularly together with EA stimulation in MSPS rats, the anxiolytic effects of the stimulation were substantially enhanced (P < 0.05). The results of this study reveal the mechanisms by which acupuncture may reduce PTSD and advance our understanding of the function of LH orexin signaling in EA's anxiolytic effects.
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Ansiolíticos , Electroacupuntura , Trastornos por Estrés Postraumático , Animales , Ratas , Trastornos por Estrés Postraumático/terapia , Ansiolíticos/farmacología , Orexinas , Área Hipotalámica Lateral , NeuronasRESUMEN
Aim: Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD. Methods: Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD. Results: GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells. Conclusion: Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.
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BACKGROUND: The mean perfusion pressure (MPP) was recently proposed to personalize tissue perfusion pressure management in critically ill patients. Severe fluctuation in MPP may be associated with adverse outcomes. We sought to determine if higher MPP variability was correlated with increased mortality in critically ill patients with CVP monitoring. METHODS: We designed a retrospective observational study and analyzed data stored in the eICU Collaborative Research Database. Validation test was conducted in MIMIC-III database. The exposure was the coefficient of variation (CV) of MPP in the primary analyses, using the first 24 hours MPP data recorded within 72 hours in the first ICU stay. Primary endpoint was in-hospital mortality. RESULTS: A total of 6,111 patients were included. The in-hospital mortality of 17.6% and the median MPP-CV was 12.3%. Non-survivors had significantly higher MPP-CV than survivors (13.0% vs 12.2%, p<0.001). After accounting for confounders, the highest MPP-CV in decile (CV > 19.2%) were associated with increased risk of hospital mortality compared with those in the fifth and sixth decile (adjusted OR: 1.38, 95% Cl: 1.07-1.78). These relationships remained remarkable in the multiple sensitivity analyses. The validation test with 4,153 individuals also confirmed the results when MPP-CV > 21.3% (adjusted OR: 1.46, 95% Cl: 1.05-2.03). CONCLUSIONS: Severe fluctuation in MPP was associated with increased short-term mortality in critically ill patients with CVP monitoring.
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Enfermedad Crítica , Humanos , Mortalidad Hospitalaria , Presión Venosa Central , Perfusión , Correlación de DatosRESUMEN
Background: Primary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN. Methods: A total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman's correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis. Results: At baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P < 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P < 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2-62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D < 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P < 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that the higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P < 0.001). Conclusion: Baseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.