Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients

Abstract Background: The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods: We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results: Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions: T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.

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Associations of urinary, glomerular, and tubular markers with the development of diabetic kidney disease in type 2 diabetes patients

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.22191 ◽

2017 ◽

Vol 32 (1) ◽

pp. e22191 ◽

Cited By ~ 4

Author(s):

Xu Jiang ◽

Qian Zhang ◽

Hua-Bin Wang ◽

Xiao-Fan Cui ◽

Rui Liu

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Tubular Markers ◽

Diabetes Patients

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Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease

Endocrine ◽

10.1007/s12020-016-1069-4 ◽

2016 ◽

Vol 55 (1) ◽

pp. 130-138 ◽

Cited By ~ 26

Author(s):

Ying Shao ◽

Huiwen Ren ◽

Chuan Lv ◽

Xiaoyu Ma ◽

Can Wu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Diabetes Patients

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Expression of Serum GRP78 and CHOP in Endoplasmic Reticulum Stress Pathways of Chinese Type 2 Diabetic Kidney Disease Patients

10.21203/rs.3.rs-25593/v1 ◽

2020 ◽

Author(s):

Ning Ma ◽

Ning Xu ◽

Dong Yin ◽

Ping Zheng ◽

Weiwei Liu ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Uric Acid ◽

Kidney Disease ◽

Endoplasmic Reticulum Stress ◽

Serum Uric Acid ◽

Diabetic Kidney Disease ◽

Serum Levels ◽

Chinese Patients ◽

Diabetic Kidney

Abstract Background The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.

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The Association of a Genetic Variant inSCAF8-CNKSR3with Diabetic Kidney Disease and Diabetic Retinopathy in a Chinese Population

Journal of Diabetes Research ◽

10.1155/2017/6542689 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Li Jin ◽

Tao Wang ◽

Song Jiang ◽

Miao Chen ◽

Rong Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Kidney Disease ◽

Mexican Americans ◽

Diabetic Kidney Disease ◽

Association Studies ◽

Genome Wide Association Studies ◽

Diabetic Kidney ◽

Diabetes Patients

Background. Genome-wide association studies found rs955333 located in 6q25.2 was associated with diabetic kidney disease in multiple ethnic populations, including European Americans, African Americans, and Mexican Americans. We aimed to investigate the association between the variant rs955333 inSCAF8-CNKSR3and DKD susceptibility in Chinese type 2 diabetes patients.Methods. The variant rs955333 was genotyped in 1884 Chinese type 2 diabetes patients. Associations of the variant rs955333 with DKD and DR susceptibility and related quantitative traits were evaluated.Results. The variant rs955333 was not associated with DKD in our samples, while subjects with genotype GG were associated with DR (P=0.047, OR = 0.55250.308,0.9911), and it also showed association with microalbuminuria (P=0.024, beta = −0.1812-0.339,-0.024).Conclusion. Our data suggests the variant rs955333 was not associated with DKD but showed association with diabetic retinopathy in Chinese type 2 diabetes patients.

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Manifestation of rs1888747 polymorphisms in the FRMD3 gene in diabetic kidney disease and diabetic retinopathy in type 2 diabetes patients

Kidney Research and Clinical Practice ◽

10.23876/j.krcp.20.190 ◽

2021 ◽

Author(s):

Chatchai Kreepala ◽

Pitirat Panpruang ◽

Rapeeporn Yodprom ◽

Teeraya Piyajarawong ◽

Krittanont Wattanavaekin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

I Gene ◽

Diabetes Patients

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Association of Diabetic Kidney Disease Markers and Urinary Beta-crossLaps in Type 2 Diabetes

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48085.15100 ◽

2021 ◽

Author(s):

Lalithambigai Arumugasamy ◽

Hetal G Patel

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Patient Group ◽

Diabetic Kidney Disease ◽

Collagen Degradation ◽

Statistical Testing ◽

Creatinine Ratio ◽

Diabetic Kidney ◽

Diabetes Patients

Introduction: Diabetic Kidney Disease (DKD) is a chronic complication in Type 2 diabetes. The Chronic Kidney Disease (CKD273) peptide classifier has been found to predict development of DKD even before microalbuminuria develops. Seventy four percent of peptides in the CKD273 classifier are Collagen degradation fragments. The Beta-CrossLaps (β-CTx) Enzyme Llinked Immunosorbent Assay (ELISA) assay detects the specific collagen degradation product, C terminal telopeptide of Type 1 collagen. In light of the Capillary Electrophoresis/Mass Spectrometry (CE-MS) findings, linking collagen degradation fragments excretion to early detection of DKD, the significance of urinary β-CTx levels as a DKD biomarker needs to be evaluated. Aim: To study the urinary excretion of β-CTx in type 2 diabetes patients and to evaluate its relation to Microalbuminuria status and estimated Glomerular Filtration Rate (eGFR) of the patients. Materials and Methods: This descriptive cross-sectional study was undertaken at a tertiary care hospital, with enrollment of 82 type 2 diabetes patients from the diabetes Out Patient Department (OPD) Participants were divided into groups based on their Urinary Albumin Creatinine Ratio (UACR) and eGFR levels. The study participants were tested for Urinary β-CTx level, UACR and eGFR. Mean or median was calculated for the parameters with normal and non-normal distribution, respectively. All statistical testing was performed on online calculators available at the site; https://www.socscistatistics.com/. Results: The median urinary β-CTx level observed was 100.6 ng/mmol of creatinine. Among the 82 participants, 15 participants had urinary β-CTx level 15pg/mL, the sensitivity of the kit. Among the remaining 67 participants, the minimum Urinary Beta-CrossLaps: Creatinine ratio observed was 2.6 ng/mmol and the maximum value observed was 2071 ng/mmol (i.e., 2.1 μg/mmol). The median urinary β-CTx level was highest (100.6 ng/mmol creatinine) in the patient group with eGFR in the normal range. The urinary β-CTx level was found to decline with decline in eGFR, with median urinary β-CTx 65.5 ng/mmol creatinine in the patient group with mildly decreased eGFR and 7.2 ng/mmol creatinine in the patient group with moderately decreased eGFR. Conclusion: The Urinary β-CTx concentration in type 2 diabetes patients is dispersed over a wide range. The Urinary β-CTx concentration correlates with the eGFR of the patient and is not influenced by age, gender or duration of diabetes. This parameter is a potential early DKD biomarker.

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