scholarly journals Urinary Microvesicle-Bound Uromodulin: A Potential Molecular Biomarker in Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Neng-jun Lou ◽  
Yi-hong Ni ◽  
Hong-ying Jia ◽  
Jing-ti Deng ◽  
Lu Jiang ◽  
...  

This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n=46); microalbuminuria group (DN1, n=32); and macroalbuminuria group (DN2, n=22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P<0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P<0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.

2018 ◽  
Vol 8 (3) ◽  
pp. 26-26
Author(s):  
Abdelbassit ElShaarawy ◽  
Maha Abdelmoneim Behairy ◽  
Somia Abdelhameed Bawady ◽  
Hoda Ahmed Abdelsattar ◽  
Eman Shadad

Background: Albuminuria showed to be a deteriorating condition in diabetic kidney disease (DKD) associated with high morbidity and mortality. A need for a novel marker for early detection of DKD development and progression becomes mandating. Objective: To study the clinical value of urinary podocin as an early marker of diabetic kidney disease and its association with severity of the disease. Patients and Methods: This study included 45 individuals with type 2 DM whose GFR >60 mL/min/1.73 m2 , recruited from Ain Shams University Hospital, Cairo, Egypt. Patients were further divided into three groups according to urinary albumin/creatinine ratio (ACR). In addition to, ten healthy volunteers serving as the control group was enrolled in the study. Routine chemistry including serum creatinine, fasting blood glucose (FBG), HbA1c, albumin, lipid profile, urine analysis, ACR and urinary podocin quantification were conducted for all participants (by ELISA method). Results: Podocin was higher in patients with ACR <30 mg/g, ACR 30-299 mg/g and ACR ≥ 300 mg/g versus healthy controls, respectively (P<0.001). Both GFR and serum albumin showed highly significant negative correlations with urinary podocin. Significant positive correlations were detected between urinary podocin with blood urea nitrogen (BUN), serum creatinine, FBG, HbA1c, cholesterol, and triglyceride levels. Conclusions: Urinary podocin is assumed to be a promising marker for early DKD detection in type 2 DM patients.


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.


2019 ◽  
Vol 18 (2) ◽  
pp. 525-532 ◽  
Author(s):  
Wei Xu ◽  
Houfa Geng ◽  
Xuekui Liu ◽  
Xiuli Wang ◽  
Rui Li ◽  
...  

Abstract Objectives Type 2 diabetes mellitus (T2DM) is sustained by insulin resistance (IR) and reduced β-cell mass, which is largely due to insulin secretory dysfunction. Wnt5a protein is essential to islet formation and β-cell migration in the development of pancreas in vertebrates. Levels of the Wnt5a protein antagonist plasma secreted frizzled-related protein 5 (Sfrp5) were elevated in patients with T2DM. However, the association between Wnt5a, T2DM patients and diabetic kidney disease (DKD) is unknown. We aim to investigate the circulating Wnt5a levels in in different clinical stages of T2DM and evaluate its correlation of duration of diabetes mellitus chronic complication. Methods A total of 329 participants (187 males, 142 females; age range 40 to 80 years) were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters evaluated in subjects with new onset T2DM, onset T2DM after treatment and DKD at different clinical phases. Results Wnt5a was significantly down-regulated in newly diagnosed T2DM patients and gradually increased after 3 months of treatment. Interesting, serum wnt5a was gradually increased in patients with long-term diabetes and kidney disease compared to patients with T2DM and onset DKD. Conclusions We speculated that the Wnt5a protein might regulate islet function and be involved in the onset of diabetes as a protective factor. It may be one of the inflammatory factors adversely involved in the progression of diabetic nephropathy.


2020 ◽  
Vol 7 (11) ◽  
pp. 4122-4131
Author(s):  
Eman Y. Morsy ◽  
Neveen L. Saad ◽  
Hesham A. Elghoneimy ◽  
Abd Alhalim G. Smeid ◽  
Azza A. Ismail

Background: The incidence of type 2 diabetes mellitus (T2DM) is increasing over the past years. Early identification and management of its complications, especially diabetic kidney disease (DKD), is of great importance. Multiple factors play a role in the pathogenesis of T2DM and DKD. We aimed to study Fetuin-A gene polymorphisms and Fetuin-A serum levels in T2DM patients with early DKD. Methods: The present work was conducted on 120 patients with T2DM (60 patients with microalbuminuria and 60 without albuminuria), and 30 healthy subjects (as a control group). Serum Fetuin-A levels were measured with ELISA. Fetuin-A, Thr256Ser and Thr248Met polymorphisms were determined by PCR-RFLP. Results: Patients with T2DM had a significantly higher mean serum Fetuin-A compared to controls (p < 0.001), while no difference was observed when comparing mean serum Fetuin-A in patients with microalbuminuria and patients without albuminuria (p = 0.916). Multivariate regression analysis demonstrated that carotid intima-media thickness (CIMT) and insulin resistance had positive correlations with serum Fetuin-A (p < 0.001 and p < 0.001, respectively). Ankle-brachial pressure index (ABPI) had a negative correlation with serum Fetuin-A (p=0.046), while Fetuin-A levels neither affected eGFR nor albuminuria. The distribution of the alleles of both polymorphisms showed increased frequency of TT (rs248) and GG (rs256) in patients without albuminuria compared to patients with microalbuminuria. Conclusion: Increased serum Fetuin-A is associated with insulin resistance and increased risk of atherosclerosis in patients with T2DM, but is not associated with the development of DKD. TT (rs248) and GG (rs256) polymorphisms may be associated with lower risk of DKD.


2020 ◽  
Vol 51 (10) ◽  
pp. 806-814 ◽  
Author(s):  
Xiangyu Wang ◽  
Huijie Zhang ◽  
Qian Zhang ◽  
Meiping Guan ◽  
Shuyue Sheng ◽  
...  

<b><i>Background:</i></b> Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD). <b><i>Methods:</i></b> We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m<sup>2</sup> and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) &#x3e;0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes. <b><i>Results:</i></b> Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m<sup>2</sup>. After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (<i>p</i> = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, <i>p</i> = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group. <b><i>Conclusion:</i></b> Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.


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 ◽  
...  

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.


2019 ◽  
Vol 95 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Guozhi Jiang ◽  
Andrea On Yan Luk ◽  
Claudia Ha Ting Tam ◽  
Fangying Xie ◽  
Bendix Carstensen ◽  
...  

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