RESUMEN

Diabetic nephropathy, as a severe microvascular complication of diabetes, manifests in four clinical types: classic, albuminuria regression, a rapid decline in kidney function (RDKF), and non-proteinuric or non-albuminuric DKD. Rapidly progressive diabetic nephropathy advances to end-stage renal disease more swiftly than the typical form, posing significant risks. However, a comprehensive understanding of rapidly progressive diabetic nephropathy is currently lacking. This article reviewed latest developments in genetic and clinical risk factors associated with rapidly progressive diabetic nephropathy, aiming to broad perspectives concerning the diagnosis and interventions of this condition.

Asunto(s)

Nefropatías Diabéticas , Progresión de la Enfermedad , Fallo Renal Crónico , Humanos , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/diagnóstico , Factores de Riesgo , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/etiología , Albuminuria/etiología , Riñón/fisiopatología , Tasa de Filtración Glomerular

RESUMEN

OBJECTIVES: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2. DESIGN: Observational cohort. SETTING: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018. PARTICIPANTS: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others). PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported. RESULTS: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2). CONCLUSIONS: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.

Asunto(s)

Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas , Tasa de Filtración Glomerular , Humanos , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/etnología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Nefropatías Diabéticas/etnología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/epidemiología , Progresión de la Enfermedad , Creatinina/orina , Creatinina/sangre , Londres/epidemiología , Etnicidad/estadística & datos numéricos , Estudios de Cohortes , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis

RESUMEN

BACKGROUND: Aim to this study is to investigate the association of Dietary Counseling, Meal Patterns, and Diet Quality (DietQ) in Patients with Type 2 Diabetes Mellitus (T2DM) with/without chronic kidney disease (CKD) in primary healthcare. METHODS: Cross-sectional study acquired data on dietary counseling and meal patterns by direct interview with a food-frequency questionnaire and one 24-h food-recall. The Healthy Eating Index (HEI) was used to classify DietQ ["good" DietQ (GDietQ, score ≥ 80) and "poor" DietQ (PDietQ, score < 80)]. PARTICIPANTS/SETTING: This study included 705 patients with T2DM: 306 with normal kidney function; 236 with early nephropathy, and 163 with overt nephropathy (ON). STATISTICAL ANALYSES PERFORMED: Multivariate linear-regression models for predicting HEI and χ2 tests for qualitative variables and one-way ANOVA for quantitative variables were employed. Mann-Whitney U and independent Student t were performed for comparisons between GDietQ and PDietQ. RESULTS: Only 18 % of the population was classified as GDietQ. Patients with ON and PDietQ vs. with GDietQ received significantly less dietary counseling from any health professional in general (45 % vs 72 %, respectively), or from any nutrition professional (36 % vs. 61 %, respectively). A better HEI was significantly predicted (F = 42.01; p = 0.0001) by lower HbA1C (ß -0.53, p = 0.0007) and better diet diversity (ß 8.09, p = 0.0001). CONCLUSIONS: Patients with more advanced stages of CKD had less nutritional counseling and worse dietary patterns, as well as more frequent PDietQ. Our findings reinforce the need for dietitians and nutritionists in primary healthcare to provide timely nutritional counseling.

Asunto(s)

Consejo , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Insuficiencia Renal Crónica/dietoterapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Anciano , Nefropatías Diabéticas/dietoterapia , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Dieta Saludable , Conducta Alimentaria/fisiología , Comidas , Dieta para Diabéticos , Dieta , Adulto

RESUMEN

The attenuation of glomerular hyperfiltration is posited to be a principal mechanism underlying the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in diabetic kidney disease. Notably, the impact of SGLT2 inhibitors on kidney hemodynamic function has been posited to vary between type 1 and type 2 diabetes. The study by Wada et al. documents that in an animal model of type 2 diabetes, SGLT2 inhibitors mitigate glomerular hyperfiltration predominantly through afferent arteriolar constriction, a process mediated by the adenosine/A1 receptor pathway. This observation is consistent with mechanisms identified in type 1 diabetes, arguing for similar methods in type 1 and 2 diabetes.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Hemodinámica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Ratas , Hemodinámica/efectos de los fármacos , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/fisiopatología , Riñón/irrigación sanguínea , Transportador 2 de Sodio-Glucosa/metabolismo , Arteriolas/efectos de los fármacos , Arteriolas/fisiopatología , Investigación Biomédica Traslacional

RESUMEN

Background: Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied. Methods: Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry. Results: GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO2 in diabetics. Conclusions: DL-sulforaphane treatment affects renal hemodynamics, improving cortical oxygen tension but not mitochondrial efficiency.

Asunto(s)

Diabetes Mellitus Experimental , Tasa de Filtración Glomerular , Hemodinámica , Isotiocianatos , Riñón , Factor 2 Relacionado con NF-E2 , Consumo de Oxígeno , Ratas Sprague-Dawley , Sulfóxidos , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Ratas , Isotiocianatos/farmacología , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Riñón/metabolismo , Sulfóxidos/farmacología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Estreptozocina , Especies Reactivas de Oxígeno/metabolismo , Circulación Renal/efectos de los fármacos , Mitocondrias/metabolismo

RESUMEN

AIMS: We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM). METHODS: 824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays. RESULTS: Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44-2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68-0.76) to 0.74 (95 %CI 0.70-0.78), p = 0.099. CONCLUSIONS: Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.

Asunto(s)

Edad de Inicio , Pueblo Asiatico , Biomarcadores , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Humanos , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Biomarcadores/sangre , Biomarcadores/orina , Adulto , Tasa de Filtración Glomerular , Uromodulina/orina , Uromodulina/sangre , alfa-Globulinas/orina , Haptoglobinas , Glicoproteínas/sangre , Glicoproteínas/orina

RESUMEN

Type 2 diabetes (T2D) is associated with increased risk for chronic kidney disease (CKD). It is estimated that 40 % of people with diabetes have CKD, which consequently leads to increase in morbidity and mortality from cardiovascular diseases (CVDs). Diabetic kidney disease (DKD) is leading cause of CKD and end-stage renal disease (ESRD) globally. On the other hand, DKD is independent risk factor for CVDs, stroke and overall mortality. According to the guidelines, using spot urine sample and assessing urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are both mandatory methods for screening of CKD in T2D at diagnosis and at least annually thereafter. Diagnosis of CKD is confirmed by persistent albuminuria followed by a progressive decline in eGFR in two urine samples at an interval of 3 to 6 months. However, many patients with T2D remain underdiagnosed and undertreated, so there is an urgent need to improve the screening by detection of albuminuria at all levels of health care. This review discusses the importance of albuminuria as a marker of CKD and cardiorenal risk and provides insights into the practical aspects of methods for determination of albuminuria in routine clinical care of patients with T2D.

Asunto(s)

Albuminuria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Albuminuria/orina , Albuminuria/diagnóstico , Diabetes Mellitus Tipo 2/orina , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/orina , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular/fisiología , Insuficiencia Renal Crónica/orina , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Biomarcadores/orina

RESUMEN

Objective: The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM). Methods: This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results. Results: A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found. Conclusion: Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

Asunto(s)

Albuminuria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Tasa de Filtración Glomerular , Estrés Oxidativo , Humanos , Estudios Transversales , Masculino , Femenino , Albuminuria/epidemiología , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Adulto , Anciano , Encuestas Nutricionales , Factores de Riesgo

RESUMEN

Diabetes mellitus is one of the leading causes of chronic kidney disease and its progression to end-stage kidney disease (ESKD). Diabetic kidney disease (DKD) is characterized by glomerular hypertrophy, hyperfiltration, inflammation, and the onset of albuminuria, together with a progressive reduction in glomerular filtration rate. This progression is further accompanied by tubulointerstitial inflammation and fibrosis. Factors such as genetic predisposition, epigenetic modifications, metabolic derangements, hemodynamic alterations, inflammation, and inappropriate renin-angiotensin-aldosterone system (RAAS) activity contribute to the onset and progression of DKD. In this context, decades of work have focused on glycemic and blood pressure reduction strategies, especially targeting the RAAS to slow disease progression. Although much of the work has focused on targeting angiotensin II, emerging data support that the mineralocorticoid receptor (MR) is integral in the development and progression of DKD. Molecular mechanisms linked to the underlying pathophysiological changes derived from MR activation include vascular endothelial and epithelial cell responses to oxidative stress and inflammation. These responses lead to alterations in the microcirculatory environment, the abnormal release of extracellular vesicles, gut dysbiosis, epithelial-mesenchymal transition, and kidney fibrosis. Herein, we present recent experimental and clinical evidence on the MR in DKD onset and progress along with new MR-based strategies for the treatment and prevention of DKD.

Asunto(s)

Nefropatías Diabéticas , Receptores de Mineralocorticoides , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Humanos , Receptores de Mineralocorticoides/metabolismo , Animales , Sistema Renina-Angiotensina , Riñón/metabolismo , Riñón/patología , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/farmacología , Transducción de Señal , Progresión de la Enfermedad

RESUMEN

OBJECTIVE: To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. RESEARCH DESIGN AND METHODS: Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. RESULTS: Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). CONCLUSIONS: Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.

Asunto(s)

Albuminuria , Diabetes Mellitus Tipo 2 , Tasa de Filtración Glomerular , Péptidos Similares al Glucagón , Fragmentos Fc de Inmunoglobulinas , Proteinuria , Proteínas Recombinantes de Fusión , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Adolescente , Niño , Proteinuria/fisiopatología , Masculino , Femenino , Albuminuria/fisiopatología , Proteínas Recombinantes de Fusión/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Hipoglucemiantes/uso terapéutico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/tratamiento farmacológico

RESUMEN

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules (PTs) purified from patients with diabetic nephropathy and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, whereas genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, whereas methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport.NEW & NOTEWORTHY Cell type-specific DNA methylation patterns in the human kidney are not known. We examined DNA methylation in proximal tubules of patients with diabetic nephropathy and revealed that oxidative stress, cytoskeleton, and metabolism genes were aberrantly methylated. The results indicate that aberrant DNA methylation in proximal tubules underlies kidney dysfunction in diabetic nephropathy. Aberrant methylation could be a target for reversing memory of poor glycemic control.

Asunto(s)

Islas de CpG , Metilación de ADN , Nefropatías Diabéticas , Epigénesis Genética , Túbulos Renales Proximales , Fenotipo , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios de Casos y Controles , Tasa de Filtración Glomerular

RESUMEN

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Tasa de Filtración Glomerular , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Anciano , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Anciano de 80 o más Años

RESUMEN

Background: The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure. Objectives: To elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress. Methods: A cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. Results: Alpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients. Conclusions: DKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.

Asunto(s)

Nefropatías Diabéticas , Microbioma Gastrointestinal , Distrés Psicológico , Humanos , Masculino , Nefropatías Diabéticas/microbiología , Nefropatías Diabéticas/psicología , Nefropatías Diabéticas/fisiopatología , Femenino , Estudios Transversales , Persona de Mediana Edad , Fallo Renal Crónico/microbiología , Fallo Renal Crónico/psicología , Fallo Renal Crónico/complicaciones , Anciano , Adulto , Estudios de Casos y Controles

RESUMEN

Background: The association of Remnant cholesterol (RC) with renal function and its progression in patients with Type 2 diabetes (T2DM) related chronic kidney disease (CKD) remains unclear. Methods: 8,678 patients with T2DM-related CKD were included in cross-sectional analysis, and 6,165 patients were enrolled in longitudinal analysis and followed up for a median of 36.0 months. The outcomes were renal composite endpoint event and rapid progression of renal function. Results: 24.54% developed a renal composite endpoint event, and 27.64% rapid progression of renal function. RC levels above 0.56 mmol/L independently increased the risk of both renal composite endpoint (HR, 1.17; 95% CIs, 1.03-1.33) and rapid progression of renal function (OR, 1.17; 95% CIs, 1.01- 1.37). TG levels above 1.65 mmol/L only increased the risk of renal composite endpoint (HR, 1.16; 95% CIs, 1.02 -1.32). TC levels above 5.21 mmol/L increased the risk of renal composite endpoint (HR, 1.14; 95% CIs, 1.01-1.29) only in patients with proteinuria≥0.5g/d. Conversely, HDL-C levels below 1.20 mmol/L or above 1.84 mmol/L increased the risk of rapid progression of renal function (OR, 0.88; 95% CIs, 0.70 -0.99) in patients with proteinuria<0.5g/d (all P<0.05). Conclusion: In patients with T2DM-related CKD, RC was an independent risk factor for progression of renal function, and maintaining it below 0.56 mmol/L could reduce the risk of renal function progression.

Asunto(s)

Colesterol , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/metabolismo , Persona de Mediana Edad , Colesterol/sangre , Estudios Transversales , Anciano , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular , Estudios Longitudinales , Estudios de Seguimiento , Riñón/fisiopatología , Riñón/metabolismo , Factores de Riesgo

RESUMEN

This study was designed to evaluate serum LC3-II, BCL-2, IL-1ß, TGF-ß1, and podocin levels in. type 2 diabetes (T2DM) patients with renal dysfunction. MATERIALS: 176 Turkish subjects were enrolled, of whom 26 were healthy, and 150 had T2DM. PATIENTS: were classified according to albumin urea ratio: 88 patients had macroalbuminuria, 20. patients had microalbuminuria, and 42 had normoalbuminuria. T2DM patients were also. classified into three groups according to proteinuria and eGFR stages. RESULTS: Increased serum LC3-II levels in patients with T2DM with increased urinary albumin. extraction and impaired renal functions. There was a strong relationship between serum. LC3-II levels and serum BCL-2, IL-1ß, TGF-ß1, and Podocin levels. The efficiency of LC3- II as a diagnostic biomarker in the differential diagnosis of DM patients with. macroproteinuria from DM patients with normoproteinuria was 75.4%. CONCLUSIONS: It was thought that increased serum LC3-II levels in T2DM patients with impaired renal. functions may cause renal podocyte damage. In these patients, serum LC3-II levels can be. evaluated as a new biomarker to follow the development of renal damage.

Asunto(s)

Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Factor de Crecimiento Transformador beta1/sangre , Biomarcadores/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/fisiopatología , Anciano , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Albuminuria/sangre , Interleucina-1beta/sangre , Adulto , Riñón/fisiopatología , Tasa de Filtración Glomerular , Proteínas de la Membrana/sangre , Proteínas Asociadas a Microtúbulos , Péptidos y Proteínas de Señalización Intracelular

RESUMEN

BACKGROUND: This study aimed to evaluate the blood pressure (BP) status, including arterial stiffness parameters, hemodynamic indicators, circadian profile, and its association with albuminuria in adolescents with type 1 diabetes mellitus (DM1). METHODS: The analysis included 46 patients, with diabetes duration of 7.38 ± 3.48 years. Ambulatory blood pressure monitoring (ABPM) was conducted using an oscillometric device, the Mobil-O-Graph, which is a Pulse Wave Analysis Monitor. RESULTS: Hypertension (HT) was diagnosed in 31 adolescents (67% of patients), primarily due to isolated nocturnal BP (21 cases, 68% of HT cases). The HT group exhibited significantly increased diastolic load (DL). Pulse wave velocity (PWV, a measure of arterial stiffness) values showed a strong correlation with both peripheral systolic BP (r = 0.954) and central systolic BP (r = 0.838). Additionally, non-dipping status was found in 61% of the HT group. Urinary albumin excretion (UAE) was positively correlated with diastolic BP (particularly nocturnal) peripheral and central BP, DL, heart rate, augmentation index (AIx@75), and nocturnal total vascular resistance (TVR). Diastolic non-dippers exhibited a significant increase in UAE. CONCLUSIONS: Hypertension is a common complication in adolescents with type 1 diabetes mellitus, primarily caused by elevated nocturnal diastolic BP. Albuminuria is mainly associated with diastolic BP, especially during the nocturnal period and in cases of diastolic non-dipping status. The association of UAE with AIx@75 and nocturnal TVR suggests the presence of early-stage vascular disease in diabetic adolescents.

Asunto(s)

Albuminuria , Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Ritmo Circadiano , Diabetes Mellitus Tipo 1 , Hipertensión , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Albuminuria/etiología , Albuminuria/fisiopatología , Albuminuria/diagnóstico , Adolescente , Femenino , Masculino , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Hipertensión/etiología , Ritmo Circadiano/fisiología , Niño , Estudios Transversales , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/diagnóstico

RESUMEN

Objective: To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1274 patients with T2DM who were enrolled in the Department of Endocrinology of the First Affiliated Hospital of Fujian Medical University between January 2017 and June 2020 were included. Patients were grouped according to VPT levels and divided into three groups, including the normal VPT group (VPT<15V), the mild-moderate elevated VPT group (VPT15~25V), and the severely elevated VPT group (VPT≥25 V). Linear correlation analysis was used to analyze the correlation between VPT and renal functions, including glomerulus markers urine microalbumin (MA) and urinary immunoglobulin G (U-IgG), and renal tubule marker α1-microglobulin (α1-MG). Chronic kidney disease (CKD) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The binary logistic regression of the relation between VPT and CKD, eGFR<60 ml/min, and UACR >30 mg/g were expressed. Results: In the mild-moderate and severely elevated VPT group, injury biomarkers of glomerulus (MA and U-IgG), renal tubule (α1-MG), and the incidence of CKD, eGFR<60 ml/min, and UACR > 30 mg/g were gradually increased compared with the normal VPT group. Furthermore, patients with diabetes and severely elevated VPT had significantly higher levels of MA (ß=197.54, p=0.042) and α1-MG (ß=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (ß=229.02, p=0.005). Patients in mild-moderate elevated VPT group (OR=1.463, 95% CI 1.005-2.127; OR=1.816, 95% CI 1.212-2.721) and severely elevated VPT group (OR=1.704, 95% CI 1.113-2.611; OR=2.027, 95% CI 1.248-3.294) are at a higher incidence of CKD and elevated levels of UACR>30mg/g compared to those in the VPT normal group. Moreover, the incidence of positive Upro was notably higher in the severely elevated VPT group (OR=1.738, 95% CI 1.182-2.556). However, this phenomenon was not observed in the incidence of eGFR <60 ml/min. Conclusion: A higher VPT is positively associated with the incidence of CKD in patients with T2DM, particularly with elevated UACR. VPT may serve as a marker for glomerulus and renal tubule injury.

Asunto(s)

Diabetes Mellitus Tipo 2 , Umbral Sensorial , Vibración , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Umbral Sensorial/fisiología , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/epidemiología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/epidemiología , Adulto , Pruebas de Función Renal , Túbulos Renales/fisiopatología , Riñón/fisiopatología

RESUMEN

BACKGROUND: Diabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes. METHODS: In this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2-9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first. RESULTS: 180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3-29.5] versus 6.5 [2.3-18.6]). CONCLUSION: Incident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Insuficiencia Cardíaca , Fallo Renal Crónico , Riñón , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Anciano , Estudios Prospectivos , Incidencia , Factores de Tiempo , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Medición de Riesgo , Singapur/epidemiología , Riñón/fisiopatología , Pronóstico , Biomarcadores/sangre

RESUMEN

These last years, the growth factor GDF15 has emerged as a key element in many different biological processes. It has been established as being produced in response to many pathological states and is now referred to as a stress-related hormone. Regarding kidney functions, GDF15 has been involved in different pathologies such as chronic kidney disease, diabetic nephropathy, renal cancer, and so on. Interestingly, recent studies also revealed a role of GDF15 in the renal homeostatic mechanisms allowing to maintain constant, as far as possible, the plasma parameters such as pH and K+ values. In this review, we recapitulate the role of GDF15 in physiological and pathological context by focusing our interest on its renal effect.

Asunto(s)

Factor 15 de Diferenciación de Crecimiento , Riñón , Humanos , Factor 15 de Diferenciación de Crecimiento/metabolismo , Riñón/metabolismo , Riñón/fisiopatología , Animales , Enfermedades Renales/metabolismo , Enfermedades Renales/fisiopatología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología

RESUMEN

Background: The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease. Methods: Our study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease. Results: After controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (ß = 0.05, 95% CI, 0.01-0.09, P = 0.012) and TPA (ß = 0.32, 95% CI, 0.10-0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (ß = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings. Conclusion: Our population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.

Asunto(s)

Nefropatías Diabéticas , Ejercicio Físico , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/fisiopatología , Adulto , Actividades Recreativas , Anciano , Tasa de Filtración Glomerular , Prevalencia