RESUMEN

ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.

Asunto(s)

Diabetes Mellitus Experimental , Nefropatías Diabéticas , Factor 2 Relacionado con NF-E2 , Syzygium , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Syzygium/química , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Células HEK293 , Estrés Oxidativo/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Productos Finales de Glicación Avanzada/metabolismo , Estreptozocina , Ratas Wistar , Antioxidantes/farmacología , Ratas Sprague-Dawley

RESUMEN

OBJECTIVE: Hospital-acquired urinary tract infections (UTIs) are common complications in patients with diabetic nephropathy (DN), leading to increased mortality and increased medical resource utilisation. This study investigated hospital-acquired UTIs in patients with DN, focusing on prevalent pathogens and drug resistance to inform clinical management. METHODOLOGY: This retrospective study analysed 141 patients with hospital-acquired UTIs admitted to The Affiliated Hospital of Qingdao University from January 1, 2013 to December 31, 2022, using the Yidu Cloud database. Among them, 109 had DN, and 32 had nondiabetic nephropathy (NDN). Patient demographics, pathogen distribution, and antibiotic resistance were statistically evaluated. RESULTS: The incidence of hospital-acquired UTIs was significantly higher in patients with DN compared to those with NDN (p < 0.0001), with a higher prevalence in women (p = 0.004). Gram-negative bacteria, particularly Escherichia coli (E. coli) and Klebsiella pneumoniae, were the primary pathogens in patients with DN and NDN. E. coli infections were more common in the DN group (p = 0.017). These pathogens exhibited high susceptibility to carbapenems, ß-lactamase inhibitors, amikacin, nitrofurantoin, and minocycline; However, they showed significant resistance to quinolones, cephalosporin, and penicillins. CONCLUSIONS: Preventing hospital-acquired UTIs in patients with DN is crucial. Effective treatment requires selecting antibacterial drugs based on pathogen resistance profiles.

Asunto(s)

Infección Hospitalaria , Nefropatías Diabéticas , Farmacorresistencia Bacteriana , Infecciones Urinarias , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Femenino , Estudios Retrospectivos , Masculino , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Persona de Mediana Edad , Nefropatías Diabéticas/complicaciones , Anciano , Antibacterianos/uso terapéutico , Antibacterianos/farmacología

RESUMEN

Diabetic nephropathy, a common and severe complication of diabetes, is the leading cause of end-stage renal disease, ultimately leading to renal failure and significantly affecting the prognosis and lives of diabetics worldwide. However, the complexity of its developmental mechanisms makes treating diabetic nephropathy a challenging task, necessitating the search for improved therapeutic targets. Intercellular communication underlies the direct and indirect influence and interaction among various cells within a tissue. Recently, studies have shown that beyond traditional communication methods, tunnel nanotubes, exosomes, filopodial tip vesicles, and the fibrogenic niche can influence pathophysiological changes in diabetic nephropathy by disrupting intercellular communication. Therefore, this paper aims to review the varied roles of intercellular communication in diabetic nephropathy, focusing on recent advances in this area.

Asunto(s)

Comunicación Celular , Nefropatías Diabéticas , Exosomas , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/metabolismo , Humanos , Animales , Exosomas/metabolismo

RESUMEN

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of GAS5 gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.

Asunto(s)

Nefropatías Diabéticas , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios de Casos y Controles , Alelos , Adulto , Estudios de Asociación Genética

RESUMEN

Background: Deposition of adipose tissue may have a promoting role in the development of diabetic complications. This study is aimed at investigating the relationship between adipose tissue thickness and risk of contrast-induced nephropathy (CIN) in patients with Type 2 diabetes mellitus (T2DM). Methods: A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty with suspicious or confirmed stable coronary artery disease were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SCF), intraperitoneal fat (IPF), and epicardial fat (ECF) were measured by color Doppler ultrasound, respectively. The association of various adipose tissues with CIN was analyzed. Results: Seventy-seven patients (12.8%) developed CIN in this cohort. Patients who developed CIN had significantly thicker PRF (13.7 ± 4.0 mm vs. 8.9 ± 3.6 mm, p < 0.001), slightly thicker IPF (p = 0.046), and similar thicknesses of SCF (p = 0.782) and ECF (p = 0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with postoperation maximal serum creatinine (sCr) (r = 0.18, p = 0.012), maximal absolute change in sCr (r = 0.33, p < 0.001), and maximal percentage of change in sCr (r = 0.36, p < 0.001). In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of PRF (0.809) for CIN was significantly higher than those of SCF (0.490), IPF (0.594), and ECF (0.512). Multivariate logistic regression analysis further confirmed that thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (odds ratio (OR) = 1.53, 95% CI: 1.38-1.71, p < 0.001). Conclusions: PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.

Asunto(s)

Medios de Contraste , Angiografía Coronaria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Medios de Contraste/efectos adversos , Persona de Mediana Edad , Anciano , Angiografía Coronaria/efectos adversos , Factores de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Enfermedades Renales/inducido químicamente , Grasa Intraabdominal/diagnóstico por imagen , Cateterismo Cardíaco/efectos adversos , Creatinina/sangre

RESUMEN

The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Grasa Intraabdominal , Obesidad , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Nefropatías Diabéticas/orina , Persona de Mediana Edad , Estudios Transversales , Grasa Intraabdominal/metabolismo , Obesidad/complicaciones , Anciano , Albuminuria , Adiposidad , Factores de Riesgo

RESUMEN

Coagulation factor XII (FXII) conveys various functions as an active protease that promotes thrombosis and inflammation, and as a zymogen via surface receptors like urokinase-type plasminogen activator receptor (uPAR). While plasma levels of FXII are increased in diabetes mellitus and diabetic kidney disease (DKD), a pathogenic role of FXII in DKD remains unknown. Here we show that FXII is locally expressed in kidney tubular cells and that urinary FXII correlates with kidney dysfunction in DKD patients. F12-deficient mice (F12-/-) are protected from hyperglycemia-induced kidney injury. Mechanistically, FXII interacts with uPAR on tubular cells promoting integrin ß1-dependent signaling. This signaling axis induces oxidative stress, persistent DNA damage and senescence. Blocking uPAR or integrin ß1 ameliorates FXII-induced tubular cell injury. Our findings demonstrate that FXII-uPAR-integrin ß1 signaling on tubular cells drives senescence. These findings imply previously undescribed diagnostic and therapeutic approaches to detect or treat DKD and possibly other senescence-associated diseases.

Asunto(s)

Senescencia Celular , Nefropatías Diabéticas , Factor XII , Integrina beta1 , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Animales , Femenino , Humanos , Masculino , Ratones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/genética , Factor XII/metabolismo , Factor XII/genética , Integrina beta1/metabolismo , Integrina beta1/genética , Túbulos Renales/metabolismo , Túbulos Renales/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Transducción de Señal

RESUMEN

OBJECTIVE: Accumulating experimental evidence has shown that resveratrol supplementation is effective for treating diabetic nephropathy (DN) in animal models. In this systematic review and meta-analysis, we assessed the effects and multiple mechanisms of resveratrol in animal models of DN. METHODS: Before September 2023, preclinical literature was systematically searched and screened across PubMed, Web of Science, EMBASE, and the Cochrane Library. Forty-two studies were included, and the risk of bias tool from SYRCLE was used to assess the methodological quality. Pooled overall effect sizes of the results were generated by STATA 16.0. RESULTS: The overall results provide preliminary evidence that the consumption of resveratrol can significantly reduce the mesangial index, glomerular basement membrane thickness, glomerular hypertrophy, serum creatinine, blood urea nitrogen, 24-h urinary protein, blood glucose, kidney index, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. In contrast, the levels of albumin and high-density lipoprotein cholesterol are significantly increased. However, resveratrol did not significantly reduce creatinine clearance or glycated hemoglobin levels. Dose-response analysis revealed that resveratrol was most effective at improving kidney function and reducing DN when administered at lower doses of ≤15 mg/kg/day or higher doses of 100-200 mg/kg/day, with significant improvements in biochemical kidney injury markers and a better effect on dysglycemia. CONCLUSIONS: The benefits of resveratrol in DN are likely due to its anti-inflammatory, antioxidant, metabolic regulatory, and autophagy-promoting effects. To confirm these findings for clinical use, further large-scale, long-term, high-quality preclinical trials are warranted to accurately assess the anti-DN effects and safety of resveratrol.

Asunto(s)

Nefropatías Diabéticas , Resveratrol , Resveratrol/farmacología , Resveratrol/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Animales , Progresión de la Enfermedad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Antioxidantes/farmacología , Antioxidantes/uso terapéutico

Asunto(s)

Tasa de Filtración Glomerular , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/tratamiento farmacológico

RESUMEN

INTRODUCTION: The four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people with high-risk of kidney failure can ensure appropriate care, education and support are in place pre-emptively. There are limited data on investigating the performance of KFRE in estimating risk of end-stage kidney disease (ESKD) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). The primary ESKD endpoint event was defined as estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and secondary endpoint eGFR <15 mL/min/1.73 m2. RESEARCH DESIGN AND METHODS: We studied 7296 people (30% women, 41% African-Caribbean, 45% Caucasian) with T2DM and CKD (eGFR median (range) 48 (15-59) mL/min/1.73 m2) were included at two hospitals in London (median follow-up 10.2 years). Time to ESKD event was the endpoint and Concordance index (C-index) was used to assess KFRE's discrimination of those experiencing ESKD from those who did not. Mean (integrated calibration index (ICI)) and 90th percentile (E90) of the difference between observed and predicted risks were used as calibration metrics. RESULTS: Of the cohort 746 (10.2%) reached ESKD primary event (135 (1.9%) and 339 (4.5%) over 2 and 5 years, respectively). Similarly, 1130 (15.5%) reached the secondary endpoint (270 (3.7%) and 547 (7.5%) over 2 and 5 years, respectively). The C-index for the primary endpoint was 0.842 (95% CI 0.836 to 0.848) and 0.816 (95% CI 0.812 to 0.820) for 2 and 5 years, respectively. KFRE 'under-predicted' ESKD risk overall and by ethnic group. Likewise, the C-index for secondary endpoint was 0.843 (0.839-0.847) and 0.801 (0.798-0.804) for 2 and 5 years, respectively. KFRE performance analysis performed more optimally with the primary endpoint with 50% enhancement of the calibration metrics than with the secondary endpoint. KFRE recalibration improved ICI by 50% and E90 by more than 78%. CONCLUSIONS: Although derived for predicting KF, KFRE also demonstrated good discrimination for ESKD outcome. Further studies are needed to identify variables/biomarkers that may improve KFRE's performance/calibration and to aid the development of other predictive models to enable early identification of people at risk of advanced stages of CKD prior to onset of KF.

Asunto(s)

Diabetes Mellitus Tipo 2 , Tasa de Filtración Glomerular , Fallo Renal Crónico , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Medición de Riesgo , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/etiología , Estudios de Seguimiento , Pronóstico , Etnicidad/estadística & datos numéricos , Adulto , Estudios de Cohortes , Progresión de la Enfermedad

RESUMEN

To explore the association between serum calcium levels within normal ranges and Diabetic Kidney Disease (DKD) in type 2 diabetes patients. In this cross-sectional study, we analyzed clinical data from type 2 diabetes patients admitted to the Endocrinology Department of the Affiliated Hospital of Qingdao University from January 1, 2021, to December 1, 2022. We measured serum calcium levels, corrected for albumin, and screened for diabetes-related complications, including DKD. The association between corrected serum calcium levels and DKD was evaluated using logistic regression, with adjustments made for potential confounders and a generalized additive model (GAM) to explore non-linear relationships, supplemented by subgroup analyses. Among the 3016 patients (52.55% male, 47.45% female), the mean corrected serum calcium was 2.29 ± 0.08 mmol/L. DKD was present in 38.73% of patients. A 0.1 mmol/L increase in corrected serum calcium was associated with a 44% increased risk of DKD (OR = 1.44, 95% CI 1.28-1.61, p < 0.0001). The GAM indicated a linear relationship between corrected serum calcium and DKD risk, consistent across subgroups. Corrected serum calcium levels were linearly associated with DKD risk in type 2 diabetes patients, underlining its potential role in risk assessment. These findings emphasize the clinical importance of monitoring serum calcium levels. However, the need for further prospective studies to confirm these findings is underscored by the study's cross-sectional design.

Asunto(s)

Calcio , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Calcio/sangre , Nefropatías Diabéticas/sangre , Anciano , Factores de Riesgo

RESUMEN

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement. METHODS: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission. RESULTS: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions. CONCLUSIONS: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis.

Asunto(s)

Enfermedades Cardiovasculares , Bases de Datos Factuales , Diabetes Mellitus Tipo 2 , Diálisis Renal , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Factores de Tiempo , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Medición de Riesgo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Registros Electrónicos de Salud

RESUMEN

Introduction: The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients. Methods: This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections. Results: In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates. Conclusion: Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important. Clinical Trial registration: ClinicalTrails.gov, NCT05888909.

Asunto(s)

COVID-19 , Nefropatías Diabéticas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , China/epidemiología , Estudios de Cohortes , COVID-19/epidemiología , COVID-19/complicaciones , Vacunas contra la COVID-19/administración & dosificación , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/complicaciones , Estudios de Seguimiento , Riñón/patología , Riñón/virología , Vacunación/estadística & datos numéricos

RESUMEN

Background: Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously. Methods: The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, ß2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760. Conclusions: The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

Asunto(s)

Biomarcadores , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/orina , Nefropatías Diabéticas/diagnóstico , Masculino , Femenino , Biomarcadores/orina , Persona de Mediana Edad , Anciano , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo

RESUMEN

BACKGROUND: To systematically evaluate the efficacy and safety of Huangkui capsule (HKC) in the treatment of diabetic nephropathy (DN). METHODS: A computerized search of 8 online databases, CNKI, VIP, WANGFANG, CBM, ChiCTR, Embase, PubMed, and Cochrane Library, was conducted from the time of database construction to June 23, 2023, and randomized controlled trials of HKC for the treatment of DN were included according to the predefined screening criteria. Literature quality was evaluated with the help of Cochrane Risk of Bias Assessment Tool, and data were analyzed by STATA/MP17 and RevMan 5.3 software. RESULTS: A total of 1543 articles were retrieved, and 45 studies were finally included, all in Chinese, with a total sample size of 4297 cases, including 2168 cases in the experimental group and 2129 cases in the control group, and the quality of all the included studies was generally low. Meta-analysis showed that (1) efficacy: effective rate: [relative risk = 1.24, 95% confidence interval (CI) (1.20, 1.29), P < .001], SCR: [standard mean difference (SMD) = -1.19, 95% CI (-1.47, -0.91), P < .001], 24 h-UTP: [SMD = -1.27, 95% CI (-1.66, -0.88), P < .001]. Other renal function, glucose metabolism, lipid metabolism, and inflammatory factors related indicators improved compared with the control group. But in the outcome index of estimated glomerular filtration rate, the addition of HKC did not have an advantage over conventional treatment alone. Estimated glomerular filtration rate: [SMD = -0.21, 95% CI (-0.80, 0.39), P = .50]. (2) Safety: There was no statistical significance in the incidence of adverse reactions between the study group with the addition of HKC and the control group. CONCLUSION: The clinical efficacy and safety of DN treated with the combination of HKC is better than that of conventional western medicine alone, but to better evaluate the efficacy and safety of HKC as an adjunctive intervention for DN, more rigorously designed large-sample, multicenter randomized controlled trials are needed to provide evidence support in the future.

Asunto(s)

Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Humanos , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento

RESUMEN

SOURCE CITATION: Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. 38785209.

Asunto(s)

Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hipoglucemiantes , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Hipoglucemiantes/uso terapéutico , Nefropatías Diabéticas/prevención & control , Masculino , Persona de Mediana Edad , Femenino

RESUMEN

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwide. While injury to the podocytes, visceral epithelial cells that comprise the glomerular filtration barrier, drives albuminuria, proximal tubule (PT) dysfunction is the critical mediator of DKD progression. Here, we report that the podocyte-specific induction of human KLF6, a zinc-finger binding transcription factor, attenuates podocyte loss, PT dysfunction, and eventual interstitial fibrosis in a male murine model of DKD. Utilizing combination of snRNA-seq, snATAC-seq, and tandem mass spectrometry, we demonstrate that podocyte-specific KLF6 triggers the release of secretory ApoJ to activate calcium/calmodulin dependent protein kinase 1D (CaMK1D) signaling in neighboring PT cells. CaMK1D is enriched in the first segment of the PT, proximal to the podocytes, and is critical to attenuating mitochondrial fission and restoring mitochondrial function under diabetic conditions. Targeting podocyte-PT signaling by enhancing ApoJ-CaMK1D might be a key therapeutic strategy in attenuating the progression of DKD.

Asunto(s)

Nefropatías Diabéticas , Túbulos Renales Proximales , Factor 6 Similar a Kruppel , Podocitos , Transducción de Señal , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/genética , Podocitos/metabolismo , Podocitos/patología , Animales , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Humanos , Ratones , Factor 6 Similar a Kruppel/metabolismo , Factor 6 Similar a Kruppel/genética , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/genética , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad

RESUMEN

The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Población Blanca , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Factor A de Crecimiento Endotelial Vascular/genética , Femenino , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Persona de Mediana Edad , Población Blanca/genética , Anciano , Genotipo , Frecuencia de los Genes , Alelos

RESUMEN

Hu antigen R (HuR) plays a key role in regulating genes critical to the pathogenesis of diabetic nephropathy (DN). This study investigates the therapeutic potential of niclosamide (NCS) as an HuR inhibitor in DN. Uninephrectomized mice were assigned to four groups: normal control; untreated db/db mice terminated at 14 and 22 weeks, respectively; and db/db mice treated with NCS (20 mg/kg daily via i.p.) from weeks 18 to 22. Increased HuR expression was observed in diabetic kidneys from db/db mice, which was mitigated by NCS treatment. Untreated db/db mice exhibited obesity, progressive hyperglycemia, albuminuria, kidney hypertrophy and glomerular mesangial matrix expansion, increased renal production of fibronectin and a-smooth muscle actin, and decreased glomerular WT-1+-podocytes and nephrin expression. NCS treatment did not affect mouse body weight, but reduced blood glucose and HbA1c levels and halted the DN progression observed in untreated db/db mice. Renal production of inflammatory and oxidative stress markers (NF-κBp65, TNF-a, MCP-1) and urine MDA levels increased during disease progression in db/db mice but were halted by NCS treatment. Additionally, the Wnt1-signaling-pathway downstream factor, Wisp1, was identified as a key downstream mediator of HuR-dependent action and found to be markedly increased in db/db mouse kidneys, which was normalized by NCS treatment. These findings suggest that inhibition of HuR with NCS is therapeutic for DN by improving hyperglycemia, renal inflammation, and oxidative stress. The reduction in renal Wisp1 expression also contributes to its renoprotective effects. This study supports the potential of repurposing HuR inhibitors as a novel therapy for DN.

Asunto(s)

Nefropatías Diabéticas , Reposicionamiento de Medicamentos , Proteína 1 Similar a ELAV , Niclosamida , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Ratones , Proteína 1 Similar a ELAV/metabolismo , Proteína 1 Similar a ELAV/genética , Masculino , Niclosamida/farmacología , Niclosamida/uso terapéutico , Riñón/metabolismo , Riñón/patología , Riñón/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Glucemia/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL

RESUMEN

BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.

Asunto(s)

Proteína HMGB1 , Hipoglucemiantes , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inhibidores , Animales , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Antiinflamatorios/uso terapéutico , Terapia Molecular Dirigida , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Resistencia a la Insulina , Receptores Toll-Like/metabolismo , Retinopatía Diabética/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Retinopatía Diabética/prevención & control , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológico