scholarly journals Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yijun Xie ◽  
Yijie Jia ◽  
Xie Cuihua ◽  
Fang Hu ◽  
Meng Xue ◽  
...  

Background. Albuminuria is an early sign but not a strong predictor of diabetic kidney disease (DKD). Owing to their high stability, urinary exosomal miRNAs can be useful predictors of the progression of early-stage DKD to renal failure; fluid biopsies are ideal for detecting abnormalities in these miRNAs. The aim of this study was to identify novel differentially expressed miRNAs as urine biomarkers for type 2 DKD by comparing between patients of type 2 diabetes (T2D) with and without macroalbuminuria. Methods. Ten patients with T2D, including five who had no renal disease and five with macroalbuminuria (DKD G1-2A3), were selected for this study. Exosome- (UExo-) derived miRNA profiles were used to identify candidate biomarkers, a subset of which was verified using quantitative reverse transcription PCR. Results. A total of 496 UExo-derived miRNA species were found to be differentially expressed (>2-fold) in patients with DKD, compared to those with T2D. A validation analysis revealed that three miRNAs (miR-362-3p, miR-877-3p, and miR-150-5p) were upregulated and one (miR-15a-5p) was downregulated. These miRNAs might regulate DKD through p53, mTOR, and AMPK pathways. Conclusions. In conclusion, UExo-derived miRNAs were altered in type 2 DKD. MiR-362-3p, miR-877-3p, miR-150-5p, and miR-15a-5p might be novel biomarkers for incipient DKD.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.


2016 ◽  
Vol 30 (8) ◽  
pp. 1585-1592 ◽  
Author(s):  
Sanaa Eissa ◽  
Marwa Matboli ◽  
Rowaida Aboushahba ◽  
Miram M. Bekhet ◽  
Yasser Soliman

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Gala-Błądzińska ◽  
Paulina Dumnicka ◽  
Beata Kuśnierz-Cabala ◽  
Katarzyna Rybak ◽  
Ryszard Drożdż ◽  
...  

Background. Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). Methods. The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) < 300 mg/g and eGFR ≥ 60 ml/min/1.73 m2. The control group included 22 nondiabetic patients with comparable age, sex, and comorbidities. uNGAL, albumin, and creatinine were measured in the first morning urine samples. uACR and uNGAL/creatinine ratios (uNCR) were calculated. Results. In the control group, maximum uNCR was 39.64 µg/g. In T2DM group, 24 patients (20%) had higher results, with the maximum value of 378.6 µg/g. Among patients with uNCR > 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (p<0.001), without difference in uACR (p=0.09). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. Conclusions. Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Lei Feng ◽  
Changqing Deng ◽  
Yanxia Li

Objective. This study aimed to explore the associations between carotid intima-media thickness (CIMT) and early-stage diabetic kidney disease (DKD) coupled with Helicobacter pylori (H. pylori) infection in type 2 diabetic patients. Methods. A cross-sectional study including 180 type 2 diabetic participants was conducted to explore the associations between CIMT and early-stage DKD coupled with H. pylori infection, and a stepwise multivariate regression analysis evaluated the correlations of CIMT with clinical and serologic parameters. Results. The type 2 diabetic patients with early-stage DKD coupled with H. pylori infections had the highest CIMT values. Apolipoprotein B (ApoB), urine albumin/creatinine ratio (UACR), and interleukin-6 (IL-6) were independent predictors of CIMT. Conclusions. Early-stage DKD coupled with H. pylori infection may synergistically lead to significant CIMT thickening in type 2 diabetic patients. Additionally, ApoB, UACR, and IL-6 levels were important independent risk factors for increased CIMT.


QJM ◽  
2018 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
S Eissa ◽  
M Matboli ◽  
R Aboushahba ◽  
M M Bekhet ◽  
Y Soliman

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Randa I. Farah ◽  
Mohammed Q. Al-Sabbagh ◽  
Munther S. Momani ◽  
Asma Albtoosh ◽  
Majd Arabiat ◽  
...  

Abstract Aim Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. Methods This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. Results Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). Conclusion Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.


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