Glomerular Hyperfiltration With Hyperglycemia in the Spontaneously Diabetic Torii (SDT) Fatty Rat, an Obese Type 2 Diabetic Model

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.

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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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Effect of pioglitazone on the early stage of type 2 diabetic nephropathy in KK/Ta mice

Metabolism ◽

10.1016/j.metabol.2004.06.016 ◽

2004 ◽

Vol 53 (11) ◽

pp. 1473-1479 ◽

Cited By ~ 41

Author(s):

Mitsuo Tanimoto ◽

Qiuling Fan ◽

Tomohito Gohda ◽

Toshihide Shike ◽

Yuichiro Makita ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Early Stage ◽

Type 2 Diabetic

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Nonalbumin proteinuria is a simple and practical predictor of the progression of early-stage type 2 diabetic nephropathy

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2016.11.009 ◽

2017 ◽

Vol 31 (2) ◽

pp. 395-399 ◽

Cited By ~ 8

Author(s):

Jong Ho Kim ◽

Sang Soo Kim ◽

In Joo Kim ◽

Min Jin Lee ◽

Yun Kyung Jeon ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Early Stage ◽

Type 2 Diabetic

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Fibroblast growth factor 21 as a predictor of early stage diabetic nephropathy in type 2 diabetic mellitus

10.36295/asro.2019.22071 ◽

2019 ◽

Vol 22 (07) ◽

pp. 01-07

Author(s):

Samah Naji ◽

Kareem Ghali ◽

Najah Hadi ◽

Maysaa Ali Abdul khaleq ◽

Mohammed Abdelhussain

Keyword(s):

Diabetic Nephropathy ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Early Stage ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Diabetic Mellitus ◽

Type 2 Diabetic Mellitus ◽

Type 2 Diabetic

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Plasma sRAGE is not associated with urinary microalbumin excretion in type 2 diabetic nephropathy at the early stage

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2009.11.002 ◽

2010 ◽

Vol 87 (2) ◽

pp. 157-160 ◽

Cited By ~ 9

Author(s):

Jiang-Yi Yu ◽

Xiao-Fei An ◽

Jing-Shun Liu ◽

Shi-Chao Ten ◽

Xin Wang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Early Stage ◽

Type 2 Diabetic

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Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen

BioMed Research International ◽

10.1155/2016/9172157 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 22

Author(s):

Kyoko Nitta ◽

Sen Shi ◽

Takako Nagai ◽

Megumi Kanasaki ◽

Munehiro Kitada ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Oral Administration ◽

Kidney Diseases ◽

Combination Group ◽

Peptide Drug ◽

Diabetic Mice ◽

Kidney Fibrosis ◽

Type 2 Diabetic

Kidney fibrosis is the final common pathway of progressive kidney diseases including diabetic nephropathy. Here, we report that the endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), the substrate of angiotensin-converting enzyme (ACE), is an orally available peptide drug used to cure kidney fibrosis in diabetic mice. We utilized two mouse models of diabetic nephropathy, streptozotocin- (STZ-) induced type 1 diabetic CD-1 mice and type 2 diabetic nephropathy modeldb/dbmice. Intervention with the ACE inhibitor imidapril, oral AcSDKP, or imidapril + oral AcSDKP combination therapy increased urine AcSDKP levels. AcSDKP levels were significantly higher in the combination group compared to those of the other groups. AcSDKP oral administration, either AcSDKP alone or in addition to imidapril, ameliorated glomerulosclerosis and tubulointerstitial fibrosis. Plasma cystatin C levels were higher in both models, at euthanasia, and were restored by all the treatment groups. The levels of antifibrotic miRs, such as miR-29 or let-7, were suppressed in the kidneys of both models; all treatments, especially the combination of imidapril + oral AcSDKP, restored the antifibrotic miR levels to a normal value or even higher. AcSDKP may be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy.

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Glomerular structural changes and structural-functional relationships at early stage of diabetic nephropathy in Japanese type 2 diabetic patients

Medical Electron Microscopy ◽

10.1007/s007950000010 ◽

2000 ◽

Vol 33 (3) ◽

pp. 115-122 ◽

Cited By ~ 9

Author(s):

T. Moriya ◽

Keiji Tanaka ◽

Rika Moriya

Keyword(s):

Diabetic Nephropathy ◽

Structural Changes ◽

Early Stage ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Functional Relationships ◽

Type 2 Diabetic

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Study of microalbuminuria as early risk marker of nephropathy in type 2 diabetic subjects

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20173006 ◽

2017 ◽

Vol 5 (7) ◽

pp. 3161 ◽

Cited By ~ 1

Author(s):

Manish K. Verma ◽

Pradeep Kumar ◽

Preeti Sharma ◽

V. K. Singh ◽

Shashi Prabha Singh

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Glycated Hemoglobin ◽

Early Stage ◽

Fasting Blood Glucose ◽

Ion Exchange Resin ◽

Risk Marker ◽

Uncontrolled Diabetes ◽

Type 2 Diabetic

Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus that lead to end-stage of kidney disease (ESKD). Detection of early-stage can slow loss of kidney function and improve patient outcomes with use of diagnostic biomarker detection of DN. Aims and objectives of this study is to evaluate the possible association between glycated hemoglobin and urinary microalbumin as a predictor of diabetic nephropathy in type 2 diabetic patients.Methods: Total 162 subjects were included in this study comprises uncontrolled diabetes 54 cases, controlled diabetes 54 cases and healthy controlled 54 controls. Micro albumin was measured by urinary microalbumin (turbidimetric immunoassay), glycated hemoglobin (HbA1c) measured by ion exchange resin method and fasting blood glucose estimated by GOD-POD method. The inclusion of age group was between 35 to 74 years. Statistical analysis was done by using SPSS, version 16.0. p values were calculated by ANOVA unpaired t-test. The p<0.05 was considered a statistically significant.Results: Urinary microalbumin levels were statistically significant increase in type 2 diabetes mellitus with nephropathy in comparison to uncontrolled diabetes mellitus and controlled diabetes mellitus (138.9±13.7 mg/l vs 67.7±14.1 mg/l and p<0.005**). HbA1c, which acts as a biomarker of diabetes was significant higher diabetic nephropathy, in comparison to uncontrolled diabetes mellitus, controlled diabetes mellitus and healthy control (8.0±1.1% vs 7.1±0.9% and 5.7±0.4%).Conclusions: The present study was demonstrated impaired glycaemic control is associated with elevations in urinary micro albumin levels and it may be considered as risk marker of diabetic nephropathy.

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