scholarly journals Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Agnieszka Kamińska ◽  
Mark Platt ◽  
Joanna Kasprzyk ◽  
Beata Kuśnierz-Cabala ◽  
Agnieszka Gala-Błądzińska ◽  
...  

The aim of this study was to check the relationship between the density of urinary EVs, their size distribution, and the progress of early renal damage in type 2 diabetic patients (DMt2). Patients were enrolled to this study, and glycated hemoglobin (HbA1c) below 7% was a threshold for properly controlled diabetic patients (CD) and poorly controlled diabetic patients (UD). Patients were further divided into two groups: diabetic patients without renal failure (NRF) and with renal failure (RF) according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled offline with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode) than UD (115 versus 109 nm; p<0.05); nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm; p<0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers.

PLoS ONE ◽  
2018 ◽  
Vol 13 (6) ◽  
pp. e0199946 ◽  
Author(s):  
Siyabonga P. Khoza ◽  
Nigel J. Crowther ◽  
Sindeep Bhana

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3405 ◽  
Author(s):  
Lubin Xu ◽  
Yang Li ◽  
Jiaxin Lang ◽  
Peng Xia ◽  
Xinyu Zhao ◽  
...  

Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]). Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.


1996 ◽  
Vol 7 (8) ◽  
pp. 1198-1206 ◽  
Author(s):  
T Miyata ◽  
Y Ueda ◽  
T Shinzato ◽  
Y Iida ◽  
S Tanaka ◽  
...  

Pentosidine is an advanced glycation end product and its formation is shown to be closely related to oxidative processes. Recent studies have shown that pentosidine levels are increased not only in plasma and matrix proteins from diabetic patients, but also markedly in nondiabetic hemodialysis patients. Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unknown. Gel filtration of uremic plasma revealed that plasma pentosidine exists in the albumin fraction (approximately 90%) and, interestingly, in free form (approximately 5%) as well. Plasma free pentosidine was undetectable in subjects with normal renal function. There was a significant correlation between the plasma levels of albumin-linked and free pentosidine in hemodialysis patients. Kinetic studies indicated that dietary pentosidine was absorbed into the circulation and that, after either oral or intravenous administration of pentosidine to intact or nephrectomized rats, the plasma free pentosidine level was closely linked to the level of renal function. These findings demonstrate that: (1) Pentosidine accumulates as albumin-linked and in free form in the circulation of uremic patients; (2) dietary pentosidine can be absorbed into the circulation, thus being one possible origin of circulating free pentosidine; (3) free pentosidine may accumulate as a result of decreased glomerular filtration; and (4) the mechanism of accumulation of albumin-linked pentosidine is not related to high glucose levels. It suggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, independent of glucose.


2014 ◽  
Vol 46 (7) ◽  
pp. 1375-1381 ◽  
Author(s):  
Huiyan Zhang ◽  
Jianyong Wang ◽  
Gui-shuang Ying ◽  
Liping Shen ◽  
Zhe Zhang

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