Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

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Inhibition of NADPH Oxidase Prevents Advanced Glycation End Product-Mediated Damage in Diabetic Nephropathy Through a Protein Kinase C- -Dependent Pathway

Diabetes ◽

10.2337/db07-1119 ◽

2007 ◽

Vol 57 (2) ◽

pp. 460-469 ◽

Cited By ~ 233

Author(s):

V. Thallas-Bonke ◽

S. R. Thorpe ◽

M. T. Coughlan ◽

K. Fukami ◽

F. Y.T. Yap ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Protein Kinase C ◽

Protein Kinase ◽

Nadph Oxidase ◽

Advanced Glycation ◽

Advanced Glycation End Product ◽

Kinase C ◽

Dependent Pathway

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Effect of tranilast in early-stage diabetic nephropathy

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfl325 ◽

2006 ◽

Vol 21 (10) ◽

pp. 2795-2799 ◽

Cited By ~ 29

Author(s):

Jun Soma ◽

Kozo Sato ◽

Harutaka Saito ◽

Yoshinori Tsuchiya

Keyword(s):

Diabetic Nephropathy ◽

Early Stage

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Evaluation of urinary TNF-α and KIM-1 biomarkers in T2DM in Upper Egypt

QJM ◽

10.1093/qjmed/hcab100.133 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Magdy EL Sharkawy ◽

Samir K Abdul-Hamid ◽

Tarek T Elmelegy ◽

Mohammed F Adawy

Keyword(s):

Diabetic Nephropathy ◽

Early Stage ◽

Clinical Syndrome ◽

Diabetic Patients ◽

University Hospitals ◽

Type 2 Diabetic Patients ◽

Cross Sectional ◽

Tnf Α ◽

Type 2 Diabetic

Abstract Background Diabetes mellitus (DM) is the most frequent cause of chronic kidney failure in both developed and developing countries. Diabetic nephropathy, is a clinical syndrome characterized by albuminuria (>300 mg/day) with permanent and irreversible decrease in glomerular filtration rate (GFR). Aim of the Work To study the role of urinary TNF-α and urine KIM-1 in type 2 diabetic patients as predictors of DN comparative with albuminuria. Patients and Methods This is a cross-sectional study which include 90 type-2 diabetic patients and 30 controls selected from the outpatient clinic of Assiut University hospitals. All patients gave an informed consent and approval for the study was obtained from the IRB committee of the Assiut Medical Faculty. The recruited patients were divided into three groups: Normo-albuminuria Group (A) (n = 30): UACR less than 30 mg/gm, Microalbuminuria Group (B) (n = 30): UACR between 30-299 mg/gm and Macro-albuminuria Group (C) (n = 30): UACR equal or more than 300 mg/gm. Assess Urinary TNF-α and urine KIM-1 in comparision with albuminuria. Results Urinary KIM-1 and urinary TNF-α are statically significant with albuminuria in patients in the early stage of diabetic nephropathy (eGFR _60 mL/min/1.73 m2).Also there are statically significance between patients with macroalbuminuria than microalbuminuria. Conclusion The results of this study recommend the use of KIM-1 and TNF-α as good predictors of early detection of development of diabetic nephropathy.

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Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0762-0341 ◽

2018 ◽

Vol 6 (01) ◽

pp. 50-55 ◽

Cited By ~ 2

Author(s):

Xin Zhao ◽

Xiao-Mei Zhang ◽

Ning Yuan ◽

Xiao-Feng Yu ◽

Li-Nong Ji

Keyword(s):

Bone Mineral Density ◽

Type 2 Diabetes ◽

Diabetic Nephropathy ◽

Bone Metabolism ◽

Early Stage ◽

Chinese Patients ◽

Creatinine Ratio ◽

Mineral Density ◽

Urine Albumin

Abstract Objective To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). Methods In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients’ data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. Results BMD at every location tested (femoral neck, trochanter, inside hip, Ward’s triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (β-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or β-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and β-CTX (p<0.05). Conclusion In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

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Rice protein ameliorates the progression of diabetic nephropathy in Goto–Kakizaki rats with high-sucrose feeding

British Journal Of Nutrition ◽

10.1017/s0007114513000354 ◽

2013 ◽

Vol 110 (7) ◽

pp. 1211-1219 ◽

Cited By ~ 21

Author(s):

Masatoshi Kubota ◽

Reiko Watanabe ◽

Hideyuki Kabasawa ◽

Noriaki Iino ◽

Akihiko Saito ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Total Cholesterol ◽

Early Stage ◽

Standard Diet ◽

Rice Protein ◽

Gk Rats ◽

Corticomedullary Junction ◽

Renal Histology ◽

Matrix Expansion ◽

High Sucrose

The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto–Kakizaki (GK) rats was investigated. GK rats at 7 weeks of age were fed 20 % RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol, TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P< 0·05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P< 0·05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P< 0·05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P< 0·05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.

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