scholarly journals Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Luca Musante ◽  
Dorota Tataruch ◽  
Dongfeng Gu ◽  
Xinyu Liu ◽  
Carol Forsblom ◽  
...  

Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.

2008 ◽  
Vol 31 (4) ◽  
pp. 255-258 ◽  
Author(s):  
Davide Bolignano ◽  
Antonio Lacquaniti ◽  
Giuseppe Coppolino ◽  
Susanna Campo ◽  
Adriana Arena ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.


2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.


2013 ◽  
Vol 30 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Midori Hasegawa ◽  
Junichi Ishii ◽  
Fumihiko Kitagawa ◽  
Kazuo Takahashi ◽  
Hiroki Hayashi ◽  
...  

2021 ◽  
Vol 84 (1) ◽  
pp. 2017-2032
Author(s):  
Halla Mohamed Allam ◽  
Haidy Essam Eldin Ahmed Zidan ◽  
Mohamed Gomaa Abdelrehim ◽  
Amira Mohamed Hamed Hassan

UK-Vet Equine ◽  
2021 ◽  
Vol 5 (5) ◽  
pp. 195-204
Author(s):  
Rachel Gough ◽  
Kate McGovern

Chronic kidney disease is a rare disease in horses, unlike humans and companion animals where it is frequently encountered. There are multiple causes, although, since the disease typically presents late in the disease process, the instigating factor is often not ascertained. Clinical signs most commonly include weight loss, ventral oedema and polyuria-polydipsia. There is a need for more sensitive markers of renal damage or dysfunction so that the disease can be detected earlier in its course. Serum symmetric dimethylarginine and neutrophil gelatinase-associated lipocalin are potential biomarkers that are being investigated in this regard. Currently, once the diagnosis has been made, treatment is supportive only, with no options to halt the progression of the disease. Although this is a terminal condition, horses can be maintained with an adequate quality of life for several years after diagnosis in some cases.


2021 ◽  
pp. 189-190
Author(s):  
G.G. Kaushik ◽  
Shubham Maheshwari ◽  
Ankita Sharma

Introduction: Serum lipocalin 2 serve as a marker for kidney function. Lipocalin 2 is found in both CKD and kidney injury and it rises in acute kidney injury (AKI) and in patients have faster decline in kidney function. Aims And Objectives: To nd out correlation and assess of serum Neutrophil gelatinase-associated lipocalin 2 (NGAL 2) in patients with stages 2 to 4 of Chronic Kidney disease. The aim of the study was NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. Material And Methods: Study involved 120 patients divided in Case group (60 patients) attended medical/ urology OPD or admitted in medical/urology ward of CKD2 – CKD4 while control group – age and sex matched healthy individuals/ stage I CKD patients was taken as control. The plasma/ serum were used for serum urea, creatinine, Cystatin C and lipocalin 2 under all aseptic precaution on receiving consent. Result:The patients of CKD included in study were having glomerulonephritis (46.7%), pyelonephritis (21.7%), diabetic kidney disease (13.3%), polycystic kidney disease (1.7%) and other causes (16.7%). CKD patients demonstrated elevated serum NGAL 159.14 ± 48.73 ng/ml, together with a rise in urea 59.9 ± 17.6 mg/dL, serum creatinine 1.56 ± 0.97 mg/dL and Cystatin C 199 ± 113 ng/ml as compared to control have serum NGAL 76.31 ± 26.34 ng/ml, urea 22.3 ± 5.7 mg/dL, serum creatinine 0.75 ± 0.14 mg/dL and Cystatin C 76 ± 17 ng/ml (P value <0.05). Conclusion: Serum NGAL closely correlates with serum Cystatin C, creatinine, and eGFR, and serve as a potential early and sensitive marker of impaired kidney function/ kidney injury.


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