scholarly journals Urinary glycated uromodulin in diabetic kidney disease

2017 ◽  
Vol 131 (15) ◽  
pp. 1815-1829 ◽  
Author(s):  
Chia-Chu Chang ◽  
Chen-Yu Chen ◽  
Ching-Hui Huang ◽  
Chia-Lin Wu ◽  
Hung-Ming Wu ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Case Control Study ◽  
Liquid Chromatography Mass Spectrometry ◽  
Diabetic Kidney ◽  
Glycation End Products ◽  
Prognostic Utility ◽  
Healthy Control ◽  
Healthy Participants ◽  
Control Study

Advanced glycation end-products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography–mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD), and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case–control study (35 with DM, 49 without). Uromodulin forms high molecular weight polymers that associate with microvesicles and exosomes. Differential centrifugation identified uromodulin in the supernatant, microvesicles, and exosomes of the urine of healthy participants, but only in the supernatant of samples from patients with DKD, suggesting that glycation influences uromodulin function. Finally, the diagnostic and prognostic utility of measuring urinary glcUMOD concentration was examined. Urinary glcUMOD concentration was substantially higher in DKD patients than non-diabetic CKD patients. Urinary glcUMOD concentration predicted DKD status, particularly in patients with CKD stages 1–3a aged <65 years and with urine glcUMOD concentration ≥9,000 arbitrary units (AU). Urinary uromodulin is apparently glycated in DKD and forms AGEs, and glcUMOD may serve as a biomarker for DKD.

Circulating miRNAs in diabetic kidney disease: case–control study and in silico analyses

2018 ◽  
Vol 56 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Taís S. Assmann ◽  
Mariana Recamonde-Mendoza ◽  
Aline R. Costa ◽  
Márcia Puñales ◽  
Balduíno Tschiedel ◽  
...  
Keyword(s):  
Kidney Disease ◽  
In Silico ◽  
Diabetic Kidney Disease ◽  
Case Control Study ◽  
Case Control ◽  
Circulating Mirnas ◽  
Diabetic Kidney ◽  
Disease Case ◽  
In Silico Analyses ◽  
Control Study

scholarly journals -866G/A and Ins/Del polymorphisms in the UCP2 gene and diabetic kidney disease: case-control study and meta-analysis

2020 ◽  
Vol 43 (2) ◽  
Author(s):  
Cristine Dieter ◽  
Taís Silveira Assmann ◽  
Natália Emerim Lemos ◽  
Eloísa Toscan Massignam ◽  
Bianca Marmontel de Souza ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Case Control Study ◽  
Meta Analysis ◽  
Case Control ◽  
Diabetic Kidney ◽  
Ucp2 Gene ◽  
Disease Case ◽  
Control Study

scholarly journals ACTIVE IMMUNOTHERAPY AGAINST RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS ATTENUATES THE PROGRESSION OF DIABETIC KIDNEY DISEASE

2021 ◽  
Vol 39 (Supplement 1) ◽  
pp. e303
Author(s):  
Tatsuhiko Azegami ◽  
Kaori Hayashi ◽  
Akihito Hishikawa ◽  
Norifumi Yoshimoto ◽  
Takashin Nakayama ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Advanced Glycation End Products ◽  
Diabetic Kidney Disease ◽  
Active Immunotherapy ◽  
Advanced Glycation ◽  
Diabetic Kidney ◽  
Glycation End Products ◽  
End Products

scholarly journals Comparison of Sevelamer and Calcium Carbonate on Lipid Profile & Hba1c in Diabetic Kidney Disease

2020 ◽  
Keyword(s):  
Calcium Carbonate ◽  
Kidney Disease ◽  
Lipid Profile ◽  
Diabetic Kidney Disease ◽  
C Reactive Protein ◽  
Advanced Glycation ◽  
Diabetic Kidney ◽  
Reactive Protein ◽  
Glycation End Products ◽  
The Mean

Diabetic is a worldwide health issue and diabetic kidney disease is a dreaded complication of the disease. Drugs that can impair intestinal absorption of advanced glycation end products (AGE) can improve glycemic control and lipid profile. Sevelamer is a calcium free phosphate binder and has postulated to have a role in prevention of absorption of age. The aim of the study was to compare the mean change HbA1c and lipid profile in diabetic kidney disease by selvelamer vs calcium carbonate. The mean of the patient was 58.53 years. Sevelamer showed a mean decrease in HbA1c and lipid profile as compared to calcium carbonate (-0.57 + 45, -8.35 ± 9.006, -1.40 ± 7.07, -4.20 ± 4.26, vs -0.08 ± 0.21, 0.10 ± 2.51, 0.62 ± 1.03, 1.00 ± 1.55). However there was a mean rise in C-reactive protein. We concluded that sevelamer caused greater mean decrease that in HBA1c and lipid profile as compared to calcium carbonate but failed to decrease C- reactive protein.

scholarly journals The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion in experimental diabetic kidney disease via promotion of endoplasmic reticulum stress

2019 ◽  
Author(s):  
Aowen Zhuang ◽  
Felicia YT Yap ◽  
Domenica McCarthy ◽  
Sally A. Penfold ◽  
Karly C. Sourris ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Advanced Glycation End Products ◽  
Diabetic Kidney Disease ◽  
Advanced Glycation ◽  
Diabetic Kidney ◽  
Glycation End Products ◽  
End Products ◽  
Foot Process

AbstractThe accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno-protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno-protection. To examine the effects of increased podocyte oligosaccharyltransferase-48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase-48kDa subunit abundance in podocytes driven by the podocin promoter. Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra-resolution microscopy of podocytes revealed denudation of foot processes where there was co-localization of oligosaccharyltransferase-48kDa subunit and advanced glycation end-products. These studies indicate that increased podocyte expression of oligosaccharyltransferase-48kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.

scholarly journals Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Wei Jing Liu ◽  
Yu Gan ◽  
Wei Fang Huang ◽  
Hong-luan Wu ◽  
Xue-qin Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Degradation Process ◽  
Beclin 1 ◽  
Dependent Manner ◽  
Lysosomal Function ◽  
Diabetic Kidney ◽  
Glycation End Products

Abstract Autophagy, the intracellular lysosomal degradation process plays a pivotal role in podocyte homeostasis in diabetic kidney disease (DKD). Lysosomal function, autophagic activity, and their actions were investigated in vitro and in vivo. We found that LC3-II- and p62-positive vacuoles accumulated in podocytes of patients with DKD. Moreover, we found that advanced glycation end products (AGEs) could increase the protein expression of LC3-II and p62 in a dose- and time-dependent manner in cultured podocytes. However, the mRNA expression of LC3B, Beclin-1 or ATG7, as well as the protein level of Beclin-1 or ATG7 did not change significantly in the AGE-treated cells compared with that in control groups, suggesting that AGEs did not induce autophagy. In addition, AGEs led to an increase in the number of autophagosomes but not autolysosomes, accompanied with a failure in lysosomal turnover of LC3-II or p62, indicating that the degradation of autophagic vacuoles was blocked. Furthermore, we observed a dramatic decrease in the enzymatic activities, and the degradation of DQ-ovalbumin was significantly suppressed after podocytes were treated with AGEs. Plasma-irregular lysosomal-associated membrane protein 1 granules accompanied with the diffusion of cathepsin D expression and acridine orange redistribution were observed in AGE-treated podocytes, indicating that the lysosomal membrane permeability was triggered. Interestingly, we also found that AGEs-induced autophagic inhibition and podocyte injury were mimicked by the specific lysosomotropic agent, l-leucyl-l-leucine methyl ester. The exacerbated apoptosis and Rac-1-dependent actin-cytoskeletal disorganization were alleviated by an improvement in the lysosomal-dependent autophagic pathway by resveratrol plus vitamin E treatment in AGE-treated podocytes. However, the rescued effects were reversed by the addition of leupeptin, a lysosomal inhibitor. It suggests that restoring lysosomal function to activate autophagy may contribute to the development of new therapeutic strategies for DKD.

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