scholarly journals Correlations between SIRT1 gene polymorphisms and diabetic kidney disease

2018 ◽  
Vol 5 (6) ◽  
pp. 171871 ◽  
Author(s):  
Xin-Ge Yue ◽  
Zai-Gang Yang ◽  
Yue Zhang ◽  
Gui-Jun Qin ◽  
Fei Liu
Keyword(s):  
Kidney Disease ◽  
Gene Polymorphisms ◽  
Diabetic Kidney Disease ◽  
Susceptibility Gene ◽  
Albumin Excretion Rate ◽  
Control Group ◽  
Diabetic Kidney ◽  
Significant Difference ◽  
Sirt1 Gene ◽  
And Control

To investigate the correlations between SIRT1 gene polymorphisms and diabetic kidney disease (DKD). There were 150 patients with DKD in the observation group (urinary albumin excretion rate (UAER) ≥ 300 mg 24 h −1 ), and 160 patients with a more than 10 year history of type 2 diabetes but without retinopathy and DKD (UAER < 30 mg 24 h −1 ) in the control group. Genotypes of three tagged single-nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1 gene in the two groups were detected. Risks of DKD for patients with the GG and GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92 times higher than that for AA genotype carriers, respectively. The risk of DKD for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21 times higher than that for AA and for AA + AG genotype carriers, respectively, and the risk of DKD for patients with allele G was 0.66 times higher than that for allele A carriers. There was no significant difference in genotype frequency of rs4746720 locus gene polymorphisms between the observation and control groups. The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype GG and allele G in the rs3818292 locus can decrease the risk of DKD.

scholarly journals ApoD and ApoA-IV, novel proteomic components in HDL of diabetic kidney disease without dialysis

2020 ◽  
Author(s):  
Monique FM Santana ◽  
Aécio LA Lira ◽  
Raphael Pinto ◽  
Carlos A Minanni ◽  
Amanda RM Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Disease ◽  
Chemical Modification ◽  
Diabetic Kidney Disease ◽  
Albumin Excretion Rate ◽  
Ldl Oxidation ◽  
Control Group ◽  
Loss Of Function ◽  
Diabetic Kidney ◽  
Traditional Risk Factors

Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR<60 plus A3 (n=25) and matched by age with control subjects (eGFR>60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more expressed in eGFR<60+A3 group in comparison to controls: apolipoprotein D (apoD) and apoA-IV. HDL from eGFR<60+A3 presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFR<60+A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group. Conclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

scholarly journals Vascular inflammation, atherosclerosis, and lipid metabolism and the occurrence of non-high albuminuria diabetic kidney disease: A cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199252
Author(s):  
Yuwei Yang ◽  
Peng Xu ◽  
Yan Liu ◽  
Xiaohong Chen ◽  
Yiyang He ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Density Lipoprotein ◽  
Endothelial Damage ◽  
Lipid Metabolism Disorder ◽  
Cross Sectional ◽  
Diabetic Kidney ◽  
Significant Difference

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease

2018 ◽  
Vol 132 (22) ◽  
pp. 2407-2422 ◽  
Author(s):  
Wenxia Yang ◽  
Ying Luo ◽  
Shikun Yang ◽  
Mengru Zeng ◽  
Shumin Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lipid Accumulation ◽  
Diabetic Kidney Disease ◽  
Mononuclear Cells ◽  
Regulatory Element ◽  
Tubular Damage ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Tnf Α ◽  
Significant Difference

Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (classes II–III) and db/db mice compared with the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry (IHC) staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol regulatory element binding protein-1 (SREBP-1) was clearly up-regulated, which was positively correlated with the tubulointerstitial damage score and inflammation. Furthermore, the urine ADRP content significantly increased in DKD patients compared with the control, which positively correlated with abnormal lipid metabolism, serum creatinine, urine N-acetyl-β-glucosaminidase (NAG), albumin excretion (albumin-to-creatinine ratio (ACR)), and tumor necrosis factor-α (TNF-α) expression. However, there was no significant difference observed in plasma ADRP levels. In addition, the expression of SREBP-1 protein was dramatically increased in peripheral blood mononuclear cells (PBMCs) isolated from DKD patients, which was also tightly correlated with urine NAG, ACR, and TNF-α levels. In vitro studies demonstrated increased ADRP and SREBP-1 expression accompanied by lipid accumulation in HK-2 cells cultured in high glucose (HG). HG induced high levels of TNF-α expression, which was partially blocked by transfection of ADRP siRNA or SREBP-1 siRNA. These data indicated that ADRP and SREBP-1 are crucial factors that mediate lipid accumulation with tubular damage and inflammation in DKD, and ectopic lipid accumulation may serve as a novel therapeutic target for amelioration of tubular injury in DKD.

Interferon Gamma +874A/T Polymorphism in Children with Idiopathic Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4539-4539
Author(s):  
Fatih Demircioglu ◽  
Hale Ören ◽  
Sefa Kizildag ◽  
Sebnem Yilmaz ◽  
Berna Atabay ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Interferon Gamma ◽  
Gene Polymorphisms ◽  
Statistical Difference ◽  
Control Group ◽  
Blood Samples ◽  
Chronic Itp ◽  
Significant Difference ◽  
Acute Itp ◽  
And Control

Abstract A recent study showed that expression of Toll-like receptor and interferon-gamma associated genes is significantly increased in patients with chronic ITP. Interferon-gamma is an important protein which takes place in immunoregulation. +874A/T polymorphism in the first introne of interferon gamma gene is found to be associated with the development and clinical phenotype of some autoimmune diseases such as diabetes mellitus, thyroiditis, multiple sclerosis, and SLE. The aim of our study was to investigate whether interferon gamma +874A/T polymorphism is a risk factor for the development of ITP and whether it affects the clinical course and response to the treatment. Thirty five children with acute ITP and 40 children with chronic ITP who were followed for at least 6 months were included. Control group consisted 90 healthy children. Two millilitres of blood sample was taken into sterile tubes containing 0.1% EDTA from each child and all blood samples were stored at −20 until analysis. DNA was isolated from blood samples and interferon gamma +874A/T polymorphism was studied with real-time PCR and LightCycler TM. Twenty one patients had AA, 35 patients had AT, and 19 patients had TT genotype. In the control group, 47 children had AA, 36 children had AT, and 7 children had TT genotype. There was a statistical difference between ITP and control group regarding the genotype (p=0.001). The frequency of A and T alleles in ITP group was 52% and 48%, respectively. The frequency of A and T alleles in control group was 72.7% and 27.8%, respectively. The frequency of allele distribution was statistically different between the ITP and control groups (p&lt;0.0001). There was a statistical significant difference between acute ITP and control group regarding the frequency of AA, AT, and TT gene polymorphisms and allele frequency (p=0.002, p=0.002). Similarly, there was a statistical significant difference between chronic ITP and control group regarding the frequency of AA, AT, and TT gene polymorphisms and allele frequency (p=0.008, p=0.002). The frequency of AA, AT, and TT gene polymorphisms and allele frequency showed no statistical difference between acute and chronic ITP groups (p=0.285, p=0.896). There was no correlation between interferon gamma +874A/T polymorphism and severity of bleeding (mild, moderate and severe) (p=0.09). There was no correlation between interferon gamma +874A/T polymorphism and response to long term treatment in patients with chronic ITP (p=0.568). In conclusion, there was a significant difference between patients with ITP and children in control group regarding interferon gamma +874A/T polymorphism and in the light of recent data involving other autoimmune disorders, we think that interferon gamma +874A/T polymorphism may be a risk factor for ITP.

scholarly journals Urine inositol pentakisphosphate 2-kinase and changes in kidney structure in early diabetic kidney disease in type 1 diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. F1484-F1492
Author(s):  
Helen C. Looker ◽  
Michael L. Merchant ◽  
Madhavi J. Rane ◽  
Robert G. Nelson ◽  
Paul L. Kimmel ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Albumin Excretion Rate ◽  
Diabetes Duration ◽  
Limit Of Quantification ◽  
Diabetic Kidney ◽  
Kidney Structure

We examined the association of urine inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPP2K) with the presence and progression of diabetic kidney disease (DKD) lesions. Urine IPP2K was measured at baseline by quantitative liquid chromatography-mass spectrometry in 215 participants from the Renin-Angiotensin System Study who had type 1 diabetes and were normoalbuminuric and normotensive with normal or increased glomerular filtration rate (GFR). Urine IPP2K was detectable in 166 participants. Participants with IPP2K below the limit of quantification (LOQ) were assigned concentrations of LOQ/√2. All concentrations were then standardized to urine creatinine (Cr) concentration. Kidney morphometric data were available from biopsies at baseline and after 5 yr. Relationships of IPP2K/Cr with morphometric variables were assessed by linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, treatment assignment, and, for longitudinal analyses, baseline structure. Baseline mean age was 29.7 yr, mean diabetes duration 11.2 yr, median albumin excretion rate 5.0 μg/min, and mean iohexol GFR 129 ml·min−1·1.73m−2. Higher IPP2K/Cr was associated with higher baseline peripheral glomerular total filtration surface density [Sv(PGBM/glom), tertile 3 vs. tertile 1 β = 0.527, P = 0.011] and with greater preservation of Sv(PGBM/glom) after 5 yr ( tertile 3 vs. tertile 1 β = 0.317, P = 0.013). Smaller increases in mesangial fractional volume ( tertile 3 vs. tertile 1 β = −0.578, P = 0.018) were observed after 5 yr in men with higher urine IPP2K/Cr concentrations. Higher urine IPP2K/Cr is associated with less severe kidney lesions at baseline and with preservation of kidney structure over 5 yr in individuals with type 1 diabetes and no clinical evidence of DKD at baseline.

scholarly journals Urinary podocin level as a predictor of diabetic kidney disease

2018 ◽  
Vol 8 (3) ◽  
pp. 26-26
Author(s):  
Abdelbassit ElShaarawy ◽  
Maha Abdelmoneim Behairy ◽  
Somia Abdelhameed Bawady ◽  
Hoda Ahmed Abdelsattar ◽  
Eman Shadad
Keyword(s):  
Kidney Disease ◽  
Serum Creatinine ◽  
Diabetic Kidney Disease ◽  
Fasting Blood Glucose ◽  
University Hospital ◽  
Control Group ◽  
High Morbidity ◽  
Diabetic Kidney ◽  
Type 2 Dm

Background: Albuminuria showed to be a deteriorating condition in diabetic kidney disease (DKD) associated with high morbidity and mortality. A need for a novel marker for early detection of DKD development and progression becomes mandating. Objective: To study the clinical value of urinary podocin as an early marker of diabetic kidney disease and its association with severity of the disease. Patients and Methods: This study included 45 individuals with type 2 DM whose GFR >60 mL/min/1.73 m2 , recruited from Ain Shams University Hospital, Cairo, Egypt. Patients were further divided into three groups according to urinary albumin/creatinine ratio (ACR). In addition to, ten healthy volunteers serving as the control group was enrolled in the study. Routine chemistry including serum creatinine, fasting blood glucose (FBG), HbA1c, albumin, lipid profile, urine analysis, ACR and urinary podocin quantification were conducted for all participants (by ELISA method). Results: Podocin was higher in patients with ACR <30 mg/g, ACR 30-299 mg/g and ACR ≥ 300 mg/g versus healthy controls, respectively (P<0.001). Both GFR and serum albumin showed highly significant negative correlations with urinary podocin. Significant positive correlations were detected between urinary podocin with blood urea nitrogen (BUN), serum creatinine, FBG, HbA1c, cholesterol, and triglyceride levels. Conclusions: Urinary podocin is assumed to be a promising marker for early DKD detection in type 2 DM patients.

scholarly journals A hyaluronan synthesis inhibitor delays progression of diabetic kidney disease in a mouse experimental model

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004642020
Author(s):  
Guillermo Selman ◽  
Laisel Martinez ◽  
Andrea Lightle ◽  
Alejandra Aguilar ◽  
Daniel Woltmann ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Glucose ◽  
Diabetic Kidney Disease ◽  
Control Diet ◽  
Experimental Period ◽  
Glomerular Injury ◽  
Synthesis Inhibitor ◽  
Diabetic Kidney ◽  
Injury Index ◽  
And Control

Background: The role of hyaluronan (HA) in the development and progression of diabetic kidney disease (DKD), as well as the precise mechanisms and consequences of HA involvement in this pathology are still to be clarified. Methods: In this study, we assayed the effects of the HA synthesis inhibitor 4-methylumbelliferone (4-MU) on the development of DKD. Diabetic type 2 model mice (eNOS-/- C57BLKS/Jdb) were fed artificial diets containing 5% 4-MU or not for 9 weeks. Plasma glucose, glomerular filtration rate (GFR), albumin to creatinine ratio (ACR), and biomarkers of kidney function and systemic inflammation were measured at baseline and after treatment. Diabetic nephropathy was further characterized in treated and control mice by histopathology. Results: Treated animals consumed a daily dose of approximately 6.2 g of 4-MU per kg of body weight. At the end of the experimental period, the 4-MU supplemented diet resulted in a significant decrease in non-fasting plasma glucose (516 [interquartile range 378-1170] vs. 1149 [875.8-1287] mg/dL, P=0.050) and a trend toward lower HA kidney content (5.6 ± 1.5 vs. 8.8 ± 3.1 ng/mg of kidney weight, P=0.070) compared to the control diet, respectively. Diabetic animals treated with 4-MU showed significantly higher GFR and lower urine ACR and plasma cystatin C levels than diabetic controls. Independent histological assessment of DKD also demonstrated a significant decrease in mesangial expansion score and glomerular injury index in 4-MU-treated mice compared to controls. Plasma glucose showed a strong correlation with kidney HA levels (r=0.66, P=0.0098). Both total hyaluronan (r=0.76, P=0.0071) and low-molecular-weight hyaluronan content (r=0.64, P=0.036) in the kidneys correlated with urine ACR in mice. Conclusion: These results show that the hyaluronan synthesis inhibitor 4-MU effectively slowed the progression of DKD and constitutes a potential new therapeutic approach to treat DKD.

scholarly journals Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toshihiro Watanabe ◽  
Yuki Fujimoto ◽  
Aya Morimoto ◽  
Mai Nishiyama ◽  
Akinori Kawai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Kidney Disease ◽  
Diabetic Patient ◽  
High Molecular Weight ◽  
Diabetic Kidney Disease ◽  
Gel Filtration ◽  
Albumin Excretion Rate ◽  
Diabetic Patients ◽  
High Molecular Weight Adiponectin ◽  
Diabetic Kidney

Abstract Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = − 0.43) and H-AN (r = − 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = − 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease.

scholarly journals Role of engulfment and cell motility 1 (ELMO1) gene polymorphism in development of diabetic kidney disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thoria A. Omar ◽  
Shimaa K. Zewain ◽  
Mohamed M. Ghonaim ◽  
Khadija A. Refaat ◽  
Dalia H. Abou-Elela
Keyword(s):  
Kidney Disease ◽  
Gene Polymorphism ◽  
Cell Motility ◽  
Diabetic Kidney Disease ◽  
Association Studies ◽  
Diabetic Patients ◽  
Genome Wide Association Studies ◽  
Diabetic Kidney ◽  
Genotype Frequencies ◽  
Significant Difference

Abstract Background Diabetic kidney disease (DKD) is a progressive kidney disease that affects diabetic patients irrespective of glycemic state or hypertension. Therefore, early detection of DKD is of critical importance. Many genome-wide association studies have identified the engulfment and cell motility 1 (ELMO1) gene as a genetic marker linked to DKD. This study aimed to investigate the association between ELMO1 rs741301 gene polymorphism and the development of DKD among Egyptian patients with type 2 diabetes mellitus (T2DM). Allele and genotype frequencies were investigated in 304 subjects by real-time PCR allelic discrimination assay: 100 DKD patients, 102 diabetic patients without DKD, and 102 healthy controls. Results GG genotype of ELMO1 (rs741301) SNP and its allele frequencies were significantly high in all diabetic patients. GG genotype had an odds ratio (OR) of 6.095 and 95% confidence interval (CI) of 2.456–15.125, p < 0.001, while the frequent allele G had an OR of 2.366 and 95% CI of 1.450–3.859, p = 0.001. No significant difference was observed between T2DM without DKD and DKD. Conclusion Our results could not establish an association between the ELMO1 rs741301 variant and the progression of DKD.

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