Time‐averaged serum uric acid and 10‐year incident diabetic kidney disease: A prospective study from China

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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Serum cell-free DNA and progression of diabetic kidney disease: a prospective study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001078 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001078 ◽

Cited By ~ 3

Author(s):

Xuan Li ◽

RenZhi Hu ◽

Ting Luo ◽

Chuan Peng ◽

Lilin Gong ◽

...

Keyword(s):

Kidney Disease ◽

Prospective Study ◽

Diabetic Kidney Disease ◽

High Sensitivity ◽

Cell Free Dna ◽

Diabetic Kidney ◽

Reactive Protein ◽

Free Dna ◽

A Prospective Study

AimsCell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD).MethodsIn this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression.ResultsIn total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=−0.219 p=0.009) and 3-year eGFR change (r=−0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89).ConclusionSerum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

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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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Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

BioMed Research International ◽

10.1155/2015/732317 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ling Wang ◽

Jia-Fen Cheng ◽

Li-Ping Sun ◽

Ya-Xiang Song ◽

Le-Hang Guo ◽

...

Keyword(s):

Uric Acid ◽

Kidney Disease ◽

Serum Uric Acid ◽

Diabetic Kidney Disease ◽

Microvascular Perfusion ◽

Renal Ultrasound ◽

Contrast Enhanced Ultrasound ◽

Protein Markers ◽

Diabetic Kidney ◽

Contrast Enhanced

Purpose.To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.Materials and Methods.79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis.Results.Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05).Conclusion.Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

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