-
Frontiers in Endocrinology 2024To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes...
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 (β=197.54, p=0.042) and α1-MG (β=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (β=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.
Topics: Humans; Diabetes Mellitus, Type 2; Female; Male; Vibration; Middle Aged; Aged; Sensory Thresholds; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Diabetic Nephropathies; Adult; Kidney Function Tests; Kidney Tubules; Kidney
PubMed: 38872969
DOI: 10.3389/fendo.2024.1357294 -
Frontiers in Aging Neuroscience 2024Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary...
PURPOSE
Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.
METHODS
Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.
RESULTS
IVW results showed that CKD, eGFR were not associated with any type of AMD ( > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, = 4.87 × 10), IgAN (OR: 1.373, 95% CI: 1.097-1.719, = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, = 1.57 × 10) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, = 7.55 × 10) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, = 7.56 × 10) and MN (OR: 1.071, 95% CI: 1.040-1.103, = 5.48 × 10).
CONCLUSION
This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.
PubMed: 38872627
DOI: 10.3389/fnagi.2024.1399666 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
Cell Biology and Toxicology Jun 2024Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is...
Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.
Topics: Epithelial-Mesenchymal Transition; Diabetic Nephropathies; RNA, Long Noncoding; Animals; Humans; Mice; Kidney Tubules; Homeodomain Proteins; Male; Epithelial Cells; Glucose; Fibrosis; Mice, Inbred C57BL; Female; Middle Aged
PubMed: 38869718
DOI: 10.1007/s10565-024-09874-5 -
Open Forum Infectious Diseases Jun 2024Foot complications are common in people with diabetes mellitus (DM), leading to increased health care utilization, heightened mortality risk, and notable recurrence...
BACKGROUND
Foot complications are common in people with diabetes mellitus (DM), leading to increased health care utilization, heightened mortality risk, and notable recurrence rates even after treatment. This retrospective cohort study aimed to investigate the impact of repeated occurrence of DM-related foot complications on the risk of all-cause mortality and to identify the potential risk factors associated with repeated events.
METHODS
People with DM admitted with foot complications (ulcer, skin and soft tissue infection, or osteomyelitis) from 2012 to 2014 were identified from Taiwan's National Health Insurance Research Database, with a 3-year follow-up for repeated events. We categorized the study subjects based on their cumulative number of hospital admissions with foot complications. Logistic regression was conducted to explore the potential risk factors associated with repeated diabetic foot events. Kaplan-Meier curves and Cox proportional hazard models were used to examine the associations between repeated diabetic foot events and all-cause mortality.
RESULTS
In this study, 28 754 eligible individuals were enrolled and classified into 3 groups: no repeated diabetic foot events (76.1%), 1 repeated event (16.0%), and 2 or more repeated events (7.9%). Logistic regression revealed that advanced age, male sex, congestive heart failure, dyslipidemia, hypertension, nephropathy, retinopathy, neuropathy, peripheral vascular disease, diabetes-related preventable hospitalizations, and outpatient visits due to diabetic foot were significantly associated with repeated events of diabetic foot complications. Compared with those with no repeated events, the adjusted hazard ratios for all-cause mortality were 1.26 (95% CI, 1.19-1.34) for 1 repeated event and 1.36 (95% CI, 1.26-1.47) for 2 or more repeated events.
CONCLUSIONS
The significant association between repeated diabetic foot and elevated mortality risk highlights the critical necessity for proactive and targeted patient care within clinical practice. More research to delve into the predictive factors related to the repeated occurrence of diabetic foot is needed to provide additional insights for prevention strategies.
PubMed: 38868313
DOI: 10.1093/ofid/ofae276 -
IET Nanobiotechnology 2024Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to...
BACKGROUND
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to explore the mechanism of exosomes in macrophages and diabetes nephropathy and the role of miRNA-34a, which might provide a new path for treating DN.
MATERIALS AND METHODS
The DN model was established, and the success of the model establishment was confirmed by detecting general indicators, HE staining, and immunohistochemistry. Electron microscopy and NanoSight Tracking Analysis (NTA) were used to see the morphology and size of exosomes. MiRNA-34a inhibitor, miRNA-34a mimics, pc-, and controls were transfected in macrophages with or without kidney exosomal. A dual-luciferase reporter gene experiment verifies the targeting relationship between miRNA-34a and . After exosomal culture, macrophages are co-cultured with normal renal tubular cells to detect renal tubular cell fibrosis. Q-PCR and western blot were undertaken to detect related RNA and proteins.
RESULTS
An animal model of diabetic nephropathy was successfully constructed. Macrophages could phagocytose exosomes. After ingesting model exosomes, M1 macrophages were activated, while M2 macrophages were weakened, indicating the model mice's kidney exosomes caused the polarization. MiRNA-34a inhibitor increased expression. MiRNA-34a expressed higher in diabetic nephropathy Model-Exo. MiRNA-34a negatively regulated . rescued macrophage polarization and renal tubular cell fibrosis.
CONCLUSION
Exosomal miRNA-34a of tubular epithelial cells promoted M1 macrophage activation in diabetic nephropathy via negatively regulating expression, which may provide a new direction for further exploration of DN treatment.
Topics: MicroRNAs; Diabetic Nephropathies; Animals; Exosomes; Mice; Macrophages; Fibrosis; Male; Kidney Tubules; Mice, Inbred C57BL; Disease Models, Animal; Diabetes Mellitus, Experimental
PubMed: 38863972
DOI: 10.1049/2024/5702517 -
Frontiers in Endocrinology 2024Serum lipids were found to be correlated with chronic kidney disease and cardiovascular disease. Here, we aimed to research the potential causal associations between...
BACKGROUND
Serum lipids were found to be correlated with chronic kidney disease and cardiovascular disease. Here, we aimed to research the potential causal associations between five serum lipid parameters and the risk of diabetic nephropathy using several Mendelian Randomization methods.
METHODS
Genetic data was obtained from the UK Biobank datasets. Causal effects were estimated using multiple MR methods. Heterogeneity and pleiotropy tests were performed.
RESULTS
MR analysis revealed that HDL-C and TG exhibited causal associations with diabetic nephropathy (<0.05). Similar trends were not observed for other lipid parameters.
CONCLUSIONS
Our research has suggested links between HDL-C, TG and diabetic nephropathy. The findings could contribute to further elucidation of the disease etiology.
STRENGTHS AND LIMITATIONS OF THIS STUDY
This article only uses Mendel randomization method to analyze the relationship between blood lipids and diabetes nephropathy, which is more convincing when combined with population data.
Topics: Humans; Mendelian Randomization Analysis; Diabetic Nephropathies; Lipids; Cholesterol, HDL; Triglycerides; Male; Female; Polymorphism, Single Nucleotide; Risk Factors; Middle Aged
PubMed: 38863932
DOI: 10.3389/fendo.2024.1358358 -
Frontiers in Endocrinology 2024The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA),...
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 (β = 0.05, 95% CI, 0.01-0.09, P = 0.012) and TPA (β = 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 (β = -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.
Topics: Humans; Male; Female; Exercise; Cross-Sectional Studies; Middle Aged; Diabetic Nephropathies; Nutrition Surveys; Adult; Leisure Activities; Aged; Glomerular Filtration Rate; Prevalence
PubMed: 38863925
DOI: 10.3389/fendo.2024.1364028 -
BMC Genomics Jun 2024Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver....
BACKGROUND
Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored. Our aim was to investigate the association of variation in both mtDNA and NEMG with CKD (and related traits), with a particular focus on diabetes.
METHODS
We used the UK Biobank (UKB) and UK-ROI, an independent collection of individuals with type 1 diabetes mellitus (T1DM) patients.
RESULTS
Fourteen mitochondrial variants were associated with estimated glomerular filtration rate (eGFR) in UKB. Mitochondrial variants and haplogroups U, H and J were associated with eGFR and serum variables. Mitochondrial haplogroup H was associated with all the serum variables regardless of the presence of diabetes. Mitochondrial haplogroup X was associated with end-stage kidney disease (ESKD) in UKB. We confirmed the influence of several known NEMG on kidney disease and function and found novel associations for SLC39A13, CFL1, ACP2 or ATP5G1 with serum variables and kidney damage, and for SLC4A1, NUP210 and MYH14 with ESKD. The G allele of TBC1D32-rs113987180 was associated with higher risk of ESKD in patients with diabetes (OR:9.879; CI:4.440-21.980; P = 2.0E-08). In UK-ROI, AGXT2-rs71615838 and SURF1-rs183853102 were associated with diabetic nephropathies, and TFB1M-rs869120 with eGFR.
CONCLUSIONS
We identified novel variants both in mtDNA and NEMG which may explain some of the missing heritability for CKD and kidney phenotypes. We confirmed the role of MT-ND5 and mitochondrial haplogroup H on renal disease (serum variables), and identified the MT-ND5-rs41535848G variant, along with mitochondrial haplogroup X, associated with higher risk of ESKD. Despite most of the associations were independent of diabetes, we also showed potential roles for NEMG in T1DM.
Topics: Humans; Male; Mitochondria; Female; Middle Aged; Genetic Predisposition to Disease; Glomerular Filtration Rate; Genetic Variation; Haplotypes; Renal Insufficiency, Chronic; DNA, Mitochondrial; Diabetes Mellitus, Type 1; Polymorphism, Single Nucleotide; Adult; Aged
PubMed: 38858654
DOI: 10.1186/s12864-024-10449-1 -
Nutrition & Diabetes Jun 2024Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose...
BACKGROUND
Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear.
METHODS
DKD mice were received different concentrations of 1,25-(OH)D for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney.
RESULTS
1,25-(OH)D could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR.
CONCLUSIONS
The protective effect of 1,25-(OH)D in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.
Topics: Animals; Gastrointestinal Microbiome; Mice; Kidney; Methylamines; Male; Receptors, Calcitriol; Mice, Knockout; Diabetic Nephropathies; Adipose Tissue; Mice, Inbred C57BL; Vitamin D; Calcitriol
PubMed: 38858392
DOI: 10.1038/s41387-024-00297-z