scholarly journals Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease

Diabetes ◽  
2015 ◽  
Vol 64 (12) ◽  
pp. 4238-4246 ◽  
Author(s):  
Jennifer N. Todd ◽  
Emma H. Dahlström ◽  
Rany M. Salem ◽  
Niina Sandholm ◽  
Carol Forsblom ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Genetic Evidence ◽  
Causal Role ◽  
Diabetic Kidney

scholarly journals CD28 Genetic Variants Increase Susceptibility to Diabetic Kidney Disease in Chinese Patients with Type 2 Diabetes: A Cross-Sectional Case Control Study

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yangyang Li ◽  
Li Jin ◽  
Jing Yan ◽  
Hong Zhang ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mendelian Randomization ◽  
Costimulatory Molecule ◽  
Causal Role ◽  
Chinese Patients ◽  
Diabetic Kidney ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

Few studies have illuminated the genetic role of T cell costimulatory molecule CD28/CD80/CTLA4 variants in diabetic kidney disease (DKD) susceptibility. We aimed to investigate the causal role of genetic polymorphisms in CD28/CD80/CTLA4 with DKD susceptibility in patients with T2DM. A total of 3253 patients with T2DM were recruited for genotyping: including 204 DKD patients and 371 controls in stage 1 and 819 DKD patients and 563 controls in stage 2; besides, 1296 T2DM patients were selected for the analysis of association between loci and DKD-related traits. A subset of 227 T2DM patients (118 patients with DKD and 109 patients without DKD) from the total population above were selected to assess serum soluble CD28 (sCD28) levels. Then, we performed a candidate gene association study to identify single-nucleotide polymorphisms (SNPs) associated with DKD susceptibility and further used those SNPs to perform Mendelian randomization analyses of serum sCD28 level and DKD susceptibility. Under additive genetic models, CD28-rs3116494 ( OR = 1.29 [95% CI 1.11, 1.51], P = 0.0011 ) and CD80-rs3850890 ( OR = 1.16 [95% CI 1.02, 1.31], P = 0.0283 ) were associated with DKD susceptibility adjusted for age, gender, body mass index (BMI), duration of diabetes, and HbA1c. CD28-rs3116494 was associated with serum sCD28 level ( β = 0.26 [95% CI 0.08, 0.44], P = 0.0043 ). The Mendelian randomization analysis showed that CD28-rs3116494 played a causal role in DKD by influencing serum sCD28 levels ( β = 1.15 [95% CI 0.46, 1.83], P = 0.0010 ). In conclusion, we identified that two novel SNPs, CD28-rs3116494 and CD80-rs3850890, were associated with DKD susceptibility. Using the Mendelian randomization analysis, our study provided evidence for a causal relationship between serum CD28 levels and DKD with T2DM in the Chinese population.

scholarly journals Role of TGF-alpha in the progression of diabetic kidney disease

2017 ◽  
Vol 312 (6) ◽  
pp. F951-F962 ◽  
Author(s):  
Josef G. Heuer ◽  
Shannon M. Harlan ◽  
Derek D. Yang ◽  
Dianna L. Jaqua ◽  
Jeffrey S. Boyles ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Neutralizing Antibodies ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Neutralizing Antibody ◽  
Diabetic Kidney

Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease.

The Role of Insulin-like Growth Factors in Diabetic Kidney Disease

1993 ◽  
Vol 22 (5) ◽  
pp. 722-726 ◽  
Author(s):  
Derek LeRoith ◽  
Haim Werner ◽  
Moshe Phillip ◽  
Charles T. Roberts
Keyword(s):  
Growth Factors ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Insulin Like Growth Factors

Role of Glycyrrhizin in the Reduction of Inflammation in Diabetic Kidney Disease

Nephron ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Vikram Thakur ◽  
Syeda Nargis ◽  
Mayra Gonzalez ◽  
Swetak Pradhan ◽  
Daniel Terreros ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney
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