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1.
BMC Prim Care ; 25(1): 197, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834994

RESUMEN

BACKGROUND: Many patients with diabetic kidney disease (DKD) do not receive evidence-based, guideline-recommended treatment shown to reduce DKD progression and complications. Proactive electronic consultations (e-consults) are an emerging intervention strategy that could potentially allow nephrologists to provide timely and evidence-based guidance to primary care providers (PCPs) engaged in early DKD care. METHODS: The objective of this study was to explore perspectives about potential barriers and facilitators associated with a proactive e-consult program to improve DKD care delivery. We conducted semi-structured qualitative interviews with PCPs across three different health systems. Interview transcripts were reviewed in a rapid qualitative analysis approach to iteratively identify, refine, and achieve consensus on a final list of themes and subthemes. RESULTS: A total of 18 interviews were conducted. PCPs across all sites identified similar challenges to delivering guideline-recommended DKD care. PCPs were supportive of the proactive e-consult concept. Three major themes emerged surrounding (1) perceived potential benefits of proactive e-consults, including educational value and improved specialist access; (2) concerns about the proactive nature of e-consults, including the potential to increase PCP workload and the possibility that e-consults could be seen as documenting substandard care; and (3) leveraging of care teams to facilitate recommended DKD care, such as engaging clinic-based pharmacists to implement specialist recommendations from e-consults. CONCLUSION: In this pre-implementation qualitative study, PCPs noted potential benefits and identified concerns and implementation barriers for proactive e-consults for DKD care. Strategies that emerged for promoting successful implementation included involving clinic support staff to enact e-consult recommendations and framing e-consults as a system improvement effort to avoid judgmental associations.


Asunto(s)
Actitud del Personal de Salud , Nefropatías Diabéticas , Médicos de Atención Primaria , Investigación Cualitativa , Humanos , Nefropatías Diabéticas/terapia , Masculino , Femenino , Nefrología , Atención Primaria de Salud , Entrevistas como Asunto , Consulta Remota
2.
BMJ Open Diabetes Res Care ; 12(3)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816203

RESUMEN

INTRODUCTION: The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45-76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial's secondary outcome of kidney disease. RESEARCH DESIGN AND METHODS: We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to <45 mL/min/1.73 m2 or need for kidney replacement therapy (KRT: dialysis or kidney transplant) during intervention and post-intervention follow-up (median 15.6 years overall). RESULTS: Incidence of eGFR <45 mL/min/1.73 m2 was lower in ILI during the intervention (HR=0.80, 95% CI=0.66 to 0.98) but not post-intervention (HR=1.03, 0.86 to 1.23) or overall (HR=0.92, 0.80 to 1.04). There were no significant treatment group differences in KRT. In prespecified subgroup analyses, age×treatment interactions were significant over total follow-up: p=0.001 for eGFR <45 mL/min/1.73 m2 and p=0.01 for KRT. The 2205 participants aged >60 years at baseline had benefit in both kidney outcomes during intervention and overall (HR=0.75, 0.62 to 0.90 for eGFR <45 mL/min/1.73 m2; HR=0.62, 0.43 to 0.91 for KRT). The absolute treatment effects were greater post-intervention: ILI reduced the rate of eGFR <45 mL/min/1.73 m2 by 0.46 and 0.76 cases/100 person-years during and post-intervention, respectively; and reduced KRT by 0.15 and 0.21 cases/100 person-years. The younger participants experienced no such post-intervention benefits. CONCLUSIONS: ILI reduced kidney disease progression during and following the active intervention in persons aged ≥60 years. ILI should be considered for reducing kidney disease incidence in older persons with type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Tasa de Filtración Glomerular , Estilo de Vida , Obesidad , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicaciones , Persona de Mediana Edad , Masculino , Femenino , Anciano , Obesidad/terapia , Sobrepeso/terapia , Sobrepeso/complicaciones , Estudios de Seguimiento , Progresión de la Enfermedad , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/prevención & control , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/epidemiología , Conducta de Reducción del Riesgo , Pronóstico
3.
J Tradit Chin Med ; 44(3): 609-619, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38767646

RESUMEN

OBJECTIVE: To assess the quality of Clinical practice guidelines (CPGs) in the context of diabetic kidney disease (DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of medlive.cn. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1 (lowest possible quality) to 7 (highest possible quality). Moreover, an overall recommendation for use was also assigned ("recommended", "recommended with modifications" or "not recommended"). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development (33%), followed by application (36%), and stakeholder involvement (51%). The highest average score was for scope and purpose (79%), followed by clarity of presentation (75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation, more than one in four CPGs for DKD had poor methodological quality. Enhanced efforts are needed to advance the rigour of development, application, and editorial independence of DKD guideline panels for most guidelines. Stakeholders, CPG developers, and CPG users should consider methodological quality while choosing CPGs, and interpret and implement their issued suggestions.


Asunto(s)
Nefropatías Diabéticas , Guías de Práctica Clínica como Asunto , Humanos , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/diagnóstico
4.
Front Endocrinol (Lausanne) ; 15: 1385872, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742202

RESUMEN

Objective: To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Methods: We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. Results: We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Conclusion: Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.


Asunto(s)
Nefropatías Diabéticas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Nefropatías Diabéticas/dietoterapia , Nefropatías Diabéticas/terapia , Suplementos Dietéticos , Metaanálisis como Asunto , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Revisiones Sistemáticas como Asunto
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 675-681, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38708500

RESUMEN

OBJECTIVE: To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. METHODS: Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats'kidneys. RESULTS: The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P < 0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P < 0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-II/I, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P < 0.05). CONCLUSION: Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.


Asunto(s)
Autofagia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Fibronectinas , Riñón , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Sirtuina 1 , Animales , Fibronectinas/metabolismo , Masculino , Ratas , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Riñón/metabolismo , Sirtuina 1/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Beclina-1/metabolismo , Creatinina/sangre , Nitrógeno de la Urea Sanguínea , Insulina , Triglicéridos/metabolismo , Triglicéridos/sangre , Colesterol/sangre , Proteínas Quinasas Activadas por AMP/metabolismo
6.
Ren Fail ; 46(1): 2352629, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38769599

RESUMEN

Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM) and has become the main cause of end-stage renal disease worldwide. In recent years, with the increasing incidence of DM, the pathogenesis of DKD has received increasing attention. The pathogenesis of DKD is diverse and complex. Extracellular vesicles (EVs) contain cell-derived membrane proteins, nucleic acids (such as DNA and RNA) and other important cellular components and are involved in intercellular information and substance transmission. In recent years, an increasing number of studies have confirmed that EVs play an important role in the development of DKD. The purpose of this paper is to explain the potential diagnostic value of EVs in DKD, analyze the mechanism by which EVs participate in intercellular communication, and explore whether EVs may become drug carriers for targeted therapy to provide a reference for promoting the implementation and application of exosome therapy strategies in clinical practice.


Asunto(s)
Nefropatías Diabéticas , Vesículas Extracelulares , Humanos , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/etiología , Vesículas Extracelulares/metabolismo , Comunicación Celular , Exosomas/metabolismo
7.
Biomed Pharmacother ; 175: 116672, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38677249

RESUMEN

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients, with its incidence continuously increasing in recent years. DN causes renal tissue damage and functional decline, expedites the aging process of the kidneys, and may ultimately progress leading to end-stage renal disease, severely impacting the patient's quality of life and prognosis. Mesenchymal stem cells (MSCs) are highly valued for their multipotent differentiation, paracrine functions, immunomodulatory effects, and capacity for tissue repair. Particularly, exosomes (Exo) derived from MSCs (MSCs-Exo) are rich in bioactive molecules and facilitate intercellular communication, participating in various physiological and pathological processes. MSCs and MSCs-Exo, in particular, have been demonstrated to have therapeutic effects in DN treatment research by encouraging tissue repair, fibrosis inhibition, and inflammation reduction. Research has shown that MSCs and MSCs-Exo have therapeutic effects in DN treatment by promoting tissue repair, inhibiting fibrosis, and reducing inflammation. Recent studies underscore the potential of MSCs and MSCs-Exo, highlighting their broad applicability in DN treatment. This review aims to provide a comprehensive summary of the scientific developments in treating DN using MSCs and MSCs-Exo from diverse sources, while also exploring their future therapeutic possibilities in detail.


Asunto(s)
Nefropatías Diabéticas , Exosomas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Exosomas/metabolismo , Exosomas/trasplante , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Células Madre Mesenquimatosas/metabolismo , Animales , Trasplante de Células Madre Mesenquimatosas/métodos , Fibrosis
8.
Curr Probl Cardiol ; 49(6): 102572, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38604416

RESUMEN

One of the most common micro vascular complications of diabetes is diabetic peripheral neuropathy (DPN). The well-recognized risk factors for DPN are hyperglycemia, dyslipidemia, and hypertension. DPN is associated with a high mortality rate and poor prognosis. Its pathogenesis is not fully understood, and clinical treatment is focused on relieving its clinical symptoms, as well as improving blood sugar control and cardiovascular risk factors. DPN and its clinically effective treatments need to be studied. Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. There was an association between DPN and DKD as well as CVD, BMI and age demonstrated. These may indicate that in case of having one diabetes complication diagnosed, it is important to screen for others, including macrovascular ones, as they may be undiagnosed due to their "silent" nature. Further studies are expected to strengthen basic research on the subject, reveal modern medical mechanisms, and provide fresh ideas and innovative methods for the treatment of DPN.


Asunto(s)
Enfermedades Cardiovasculares , Nefropatías Diabéticas , Neuropatías Diabéticas , Humanos , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/etiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/diagnóstico , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/complicaciones , Factores de Riesgo , Pronóstico
10.
Medicina (Kaunas) ; 60(3)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38541098

RESUMEN

Background and Objectives: Diabetes is one of the most common diseases dealt with by physicians in primary healthcare centers (PHCs). The disease is associated with macrovascular and microvascular complications, especially in those with long disease duration and uncontrolled diabetic nephropathy, which is one of the most common microvascular complications among diabetic patients. This investigation assessed the practices of physicians working at PHCs in terms of diabetic nephropathy screening, management, and referral. Materials and Methods: This study is a cross-sectional investigation targeting physicians working at PHCs in the Jazan region of Saudi Arabia between March and August of 2023. Data were collected via a self-administered questionnaire, which was distributed via online platforms. The questionnaire included sections measuring physicians' demographic data and associated factors regarding training, the availability of resources, and practices in diabetic nephropathy, including screening, management, and referral. Chi-squared tests were used to assess associations between the practices of physicians and the measured demographics. Result: A total of 234 physicians participated in the investigation. The median age of the participants was 35 years. The adherence level of practice toward diabetic nephropathy according to American Diabetes Association (ADA) guidelines ranged from 40 points (the highest adherence level of participants) to 19 points (the lowest adherence level of participants), with a median of 33 points. Higher adherence levels were noted among physicians in Saudi Arabia, physicians with higher education levels, physicians specializing as family physicians or diabetologists, physicians who reported attending online and on-site training at diabetic centers, physicians who reported continuous access to urine and serum creatinine tests, and physicians who reported continuous access to the American Diabetes Association guidelines (p < 0.05). Conclusions: There are several factors associated with the level of adherence in diabetic nephropathy practice, such as physicians' education level, specialty, training, and access to guidelines. The findings suggest the need for more training for PHC physicians in the care of patients affected by or at risk of diabetic nephropathy.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Médicos , Humanos , Adulto , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Arabia Saudita , Estudios Transversales , Atención Primaria de Salud
11.
Adv Skin Wound Care ; 37(4): 203-210, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38506581

RESUMEN

OBJECTIVE: To determine the prevalence and risk factors of foot ulceration in patients receiving hemodialysis treatment. METHODS: A total of 180 patients who received hemodialysis treatment in two state hospitals and a private health center between April 2017 and September 2017 were included in the study. The researchers collected data using a patient information form and by conducting physical evaluation of the lower extremities. They used the diabetic foot risk assessment algorithm to classify risk according to the data obtained. RESULTS: Of the patients receiving hemodialysis treatment, 6.7% had foot ulceration, 19.4% had a history of foot ulceration, and 8.3% had a history of hospitalization associated with ulceration in a lower extremity. Infected foot ulceration was the most common (6.1%) cause of hospitalizations. In the group with current or past foot ulceration, diabetic nephropathy was the most common etiologic factor of end-stage kidney disease (48.6%); there was a significant between-group difference in diabetic nephropathy (P < .05). Etiologic factors had a significant effect on foot ulcerations: As determined by univariate logistic regression, diabetes (odds ratio [OR], 2.727; P < .05), presence of neuropathy (OR, 4.208; P < .05), low-density lipoprotein cholesterol (OR, 1.013; P < .05), and serum albumin (OR, 0.302; P < .036) all had a statistically significant effect on the presence of foot ulcerations. CONCLUSIONS: Patients receiving hemodialysis treatment are at high risk for foot ulceration. Therefore, patient awareness strategies should be expanded to include individuals with end-stage renal disease regardless of diabetes status. Clinical and dialysis nurses should educate these patients about foot ulcerations and foot health to prevent ulcer development.


Asunto(s)
Nefropatías Diabéticas , Fallo Renal Crónico , Humanos , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/terapia , Factores de Riesgo , Diálisis Renal/efectos adversos , Fallo Renal Crónico/terapia , Algoritmos
12.
J Health Popul Nutr ; 43(1): 40, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454510

RESUMEN

OBJECTIVE: To explore the effect of the hospital-community-home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN). METHOD: A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention. RESULTS: After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05). CONCLUSION: The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/terapia , Glucemia , Cooperación del Paciente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Hospitales
13.
Stem Cell Res Ther ; 15(1): 66, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443965

RESUMEN

BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. METHODS: A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. RESULTS: Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-ß1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-ß1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. CONCLUSIONS: Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-ß1 and restoration of intra-renal autophagy.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Riñón/anomalías , Células Madre Mesenquimatosas , Anomalías Urogenitales , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Nefropatías Diabéticas/terapia , Inyecciones Intravenosas , Factor de Crecimiento Transformador beta1 , Diabetes Mellitus Experimental/terapia , Interleucina-6 , Factor de Necrosis Tumoral alfa , Autofagia , Fibrosis , Serina-Treonina Quinasas TOR
14.
Am J Nephrol ; 55(3): 389-398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38423000

RESUMEN

INTRODUCTION: Autologous cell-based therapies (CBT) to treat chronic kidney disease (CKD) with diabetes are novel and can potentially preserve renal function and decelerate disease progression. CBT dosing schedules are in early development and may benefit from individual bilateral organ dosing and kidney-dependent function to improve efficacy and durability. The objective of this open-label, phase 2 randomized controlled trial (RCT) is to evaluate participants' responses to rilparencel (Renal Autologous Cell Therapy-REACT®) following bilateral percutaneous kidney injections into the kidney cortex with a prescribed dosing schedule versus redosing based on biomarker triggers. METHODS: Eligible participants with type 1 or 2 diabetes and CKD, eGFR 20-50 mL/min/1.73 m2, urine albumin-to-creatinine ratio (UACR) 30-5,000 mg/g, hemoglobin >10 g/dL, and glycosylated hemoglobin <10% were enrolled. After a percutaneous kidney biopsy and bioprocessing ex vivo expansion of selected renal cells, participants were randomized 1:1 into two cohorts determined by the dosing scheme. Cohort 1 receives 2 cell injections, one in each kidney 3 months apart, and cohort 2 receives one injection and the second dose only if there is a sustained eGFR decline of ≥20 mL/min/1.73 m2 and/or UACR increase of ≥30% and ≥30 mg/g, confirmed by re-testing. CONCLUSION: The trial is fully enrolled with fifty-three participants. Cell injections and follow-up clinical visits are ongoing. This multicenter phase 2 RCT is designed to investigate the efficacy and safety of rilparencel with bilateral kidney dosing and compare two injection schedules with the potential of preserving or improving kidney function and delaying kidney disease progression among patients with stages 3a-4 CKD with diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Nefropatías Diabéticas/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Tasa de Filtración Glomerular , Riñón , Masculino , Trasplante Autólogo/métodos , Persona de Mediana Edad , Femenino , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Adulto , Resultado del Tratamiento
16.
J Mol Med (Berl) ; 102(4): 537-570, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38418620

RESUMEN

Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs' action in this disease progression. KEY MESSAGES: Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease. Mesenchymal stem cells alleviate in animal models having diabetic kidney disease. Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Adulto , Animales , Humanos , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/metabolismo , Riñón , Trasplante de Células Madre Mesenquimatosas/métodos , Regeneración , Antiinflamatorios/farmacología , Células Madre Mesenquimatosas/metabolismo , Diabetes Mellitus/metabolismo
17.
J Infect Chemother ; 30(8): 812-814, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38316186

RESUMEN

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.


Asunto(s)
Antibacterianos , Eliminación de Componentes Sanguíneos , Lipoproteínas LDL , Diálisis Renal , Vancomicina , Humanos , Vancomicina/sangre , Vancomicina/uso terapéutico , Vancomicina/farmacocinética , Eliminación de Componentes Sanguíneos/métodos , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Lipoproteínas LDL/sangre , Masculino , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicaciones , Persona de Mediana Edad
18.
Exp Clin Transplant ; 22(Suppl 1): 128-140, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38385386

RESUMEN

OBJECTIVES: Diabetes knowledge among kidney transplant recipients with posttransplant diabetes has not been clearly assessed. We evaluated whether diabetes education in kidney transplant recipients with posttransplant diabetes affected self-care, metabolic control variables, and reversibility of early diabetic microangiopathies. MATERIALS AND METHODS: In this prospective randomized controlled study, we enrolled 210 renal transplant recipients with posttransplant diabetes. Group 1 patients (n = 140) received structured diabetes education, and group 2 patients (n = 70) received conventional education. Patient data were collected through patient identification and metabolic control parameter forms and a diabetes self-care scale questionnaire (scores between 0 and 7). RESULTS: Diet knowledge improved and waist circumference was reduced with mild to moderate exercise in group 1 (P < .001), despite no differences between the 2 groups in mean body weight or body mass index. Patients in group 1 (structured diabetes education with repeated reinforcement) showed significant improvement in healthy lifestyle parameter scores versus group 2 (P < .05) and versus values before education (P < .05). At end of study, these achievements were translated into proper blood sugar monitoring, management of both hypoand hyperglycemia, improvements in logbook use and healthy sharp disposal, Ramadan fasting, sick day management, and knowledge on the importance of HbA1c (P < .05), which translated to decrease of HbA1c in group 1 by 1.35%. In group 1, proteinuria decreased significantly compared with before education and compared with group 2 values (P = .016). Diabetic retinopathy and neuropathy remained comparable between groups (P > .05). CONCLUSIONS: Structured diabetes education improved lifestyle knowledge, self-care diabetes management, and metabolic control variables among kidney transplant recipients with posttransplant diabetes. Structured diabetes education also resulted in partial reversibility of the present early diabetic nephropathy. We recommended such education to be delivered to all kidney transplant recipients with diabetes.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Hemoglobina Glucada , Autocuidado , Estudios Prospectivos , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/terapia , Estilo de Vida Saludable
19.
PeerJ ; 12: e16915, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38390389

RESUMEN

Background: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Methods: Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. Results: In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n = 74), NDKD (n = 109), and DN + NDKD (n = 85) groups. The most frequent NDKD was membranous nephropathy (MN) (n = 45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n = 34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p < 0.05). Multifactorial analysis showed that increased SBP [HR (95% CI): 1.018(1.002-1.035), p = 0.025], lower Hb [HR(95% CI): 0.979(0.961-0.997), p = 0.023], higher glycosylated hemoglobin [HR(95% CI): 1.338(1.080-1.658), p = 0.008] and reduced serum ALB [HR(95% CI): 0.952(0.910-0.996), p = 0.032] were risk factors for outcomes in the T2DM patients with CKD. Conclusions: This research based on a Chinese cohort demonstrated that the risk of endpoint events differed among DN, NDKD, and DN+NDKD patients. In T2DM patients with CKD, DN patients displayed worse kidney prognosis than those with NDKD or DN + NDKD. Increased SBP, higher glycosylated hemoglobin, lower Hb, and decreased serum ALB may be correlated with adverse kidney outcomes in T2DM patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Nefropatías Diabéticas/terapia , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicaciones
20.
Arch Esp Urol ; 77(1): 104-112, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38374020

RESUMEN

BACKGROUND: This study aims to elucidate the microRNA (miRNA)-messenger RNA (mRNA)-transcription factors (TFs) network relevant to diabetic nephropathy (DN). METHODS: To investigate the molecular mechanisms underlying DN, we conducted an extensive analysis using a Gene Expression Omnibus (GEO) database, specifically GSE51784, GSE30528, GSE30529 and GSE1009. RNA samples from 66 subjects were analysed to identify differentially expressed mRNAs (DEGs) and microRNAs (DEMs) between individuals with DN and healthy controls. The data underwent preprocessing, followed by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA) to unveil enriched pathways. Additionally, we constructed protein-protein interaction networks and subnetworks of modules to identify key molecular players. RESULTS: A total of 163 DEMs and 188 DEGs were identified among the four datasets. Furthermore, we identified 37 hub genes with high connectivity and four TFs, namely E1A Binding Protein P300 (EP300), SP100 Nuclear Antigen (SP100), Nuclear Receptor Subfamily 6 Group A Member 1 (NR6A1) and Jun Dimerization Protein 2 (JDP2), which may play crucial roles in the molecular pathogenesis of DN. Additionally, we constructed a co-regulatory network involving miRNAs, mRNAs and TFs, revealing potential involvement of pathways such as the Mitogen-Activated Protein Kinase (MAPK) signalling pathway, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway and metabolic pathways in the pathogenesis of DN. Finally, using a docking model, we established drug-gene interactions involving key genes in the network, providing potential insights into therapeutic options. CONCLUSIONS: This study explores a gene regulation network of miRNA-mRNA-TFs, identifying potential molecular targets in the aetiology of DN. It also suggests potential targets for genetic counselling and prenatal diagnosis for DN.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , MicroARNs , Humanos , MicroARNs/genética , Perfilación de la Expresión Génica , ARN Mensajero/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/terapia , Fosfatidilinositol 3-Quinasas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
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