scholarly journals Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yunqiang He ◽  
Ziqiang Xu ◽  
Mingshi Zhou ◽  
Minmin Wu ◽  
Xuehai Chen ◽  
...  

Objective. Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN.Methods. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group), the insulin-treated group (IN group), and the untreated group (DN group). Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM) detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels.Results. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM) were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased.Conclusions. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunqiang He ◽  
Ziqiang Xu ◽  
Hongxing Fu ◽  
Bin Chen ◽  
Silu Wang ◽  
...  

Objective.Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model.Methods.A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1) in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules.Results.The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated.Conclusions.The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.


2016 ◽  
Vol 41 (3) ◽  
pp. 125-130
Author(s):  
Mahbuba Shirin ◽  
Mofazzal Sharif ◽  
Ayeshna Gurung ◽  
Anindita Datta

Diabetes mellitus is one of the systemic diseases affecting the kidneys. Diabetic nephropathy is a serious microvascular complication of diabetes mellitus. It is the most important cause of death in type I diabetic patients, of whom 30%-40% eventually develop end-stage renal failure and 40% of type II diabetics are at risk of developing diabetic nephropathy. So, diagnosis of diabetic nephropathy is paramount for the survivability of the diabetic patients not only because of the consequences of renal progression but also because of the strong association with the risk of developing cardiovascular disease. A total number of 53 subjects were enrolled in this present cross sectional study in the department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration of Nephrology and Medicine of the same institution during two years (2011-13) aim to evaluate the diagnostic usefulness of renal resistive index (RI) by duplex Doppler ultrasonography for detection of renal dysfunction in diabetic patients. Clinically diagnosed diabetic patients having diabetic nephropathy referred to the department of Radiology and Imaging in BSMMU for ultrasonography of Kidneys, Ureters and Bladder (KUB) region or whole abdomen were selected as sample. Biochemical reports (Serum creatinine and Urinary albumin) and the RI value of intrarenal artery were correlated and analyzed. Only those patients biochemically were diagnosed as having diabetic nephropathy was included. Those with incomplete data, hydro nephrosis and renal calculus were excluded. Both the kidneys were visualized by commercially available real time scanner (GE Voluson) equipped with a curvilinear transducer operating at 3.5 MHz First Gray scale ultrasonography was done followed by Color Doppler of intra renal artery and then RI was measured. Majority (45.3%) patients were in 6th decade with the mean age was of 52.66±7.4 years and ranging from 38 to 65 years in patients. Male was found to be 54.7% of diabetic patients with male to female ratio 1.2:1. Resistive index of (? 0.7) was found in 73.6% patients with diabetes with the mean resistive index of 0.71±0.04. Positive correction between resistive index with serum creatinine (r=0.581, p<0.01) and albuminuria (r=0.725, p<0.01) were observed. It can be concluded that Resistive Index measured by duplex Doppler ultrasonography is useful diagnostic modality for detection of renal dysfunction in diabetic nephropathy patients. Resistive Index has value in identifying diabetic patients who are developing nephropathy and can be used as an additional diagnostic tool. Also it is well correlated with Serum Creatinine and Albuminuria which are the biochemical parameters to diagnose diabetic nephropathy.


2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.


2021 ◽  
Vol 10 (25) ◽  
pp. 1866-1870
Author(s):  
Bhuneshwar Yadav ◽  
Shashidhar K.N ◽  
Raveesha A ◽  
Muninarayana C.

BACKGROUND Increased levels of urinary biomarkers can be detected in type 2 diabetic patients before the onset of significant albuminuria and may be used as an early marker of renal injury in diabetic nephropathy (DN) which would play a significant role for the effective management and treatment approaches in diabetic care. We wanted to evaluate cystatin C and microalbumin as effective early biomarkers in assessing nephropathy in patients with type 2 diabetes mellitus in this study. METHODS A cross-sectional study was conducted among 180 subjects grouped into healthy controls, clinically proven T2DM without nephropathy and type 2 DM with nephropathy comprising 60 participants in each group. Fasting and postprandial blood samples and urine samples were collected and analysed by standard methods. eGFR was calculated using CKD-EPI 2012 equation. IBM - SPSS version 20 was used for statistical analysis. RESULTS Diabetic nephropathy patients had significantly elevated serum cystatin C and microalbumin (2.43 ± 0.59, 700.5 ± 591.8 mg / L, respectively), compared to T2DM (0.98 ± 0.26, 63.7 ± 102.9 mg / L, respectively), and the control study subjects (0.81 ± 0.16, 11.15 ± 8.9 mg / L, respectively). Serum cystatin C showed AUC of 0.994 (95 % CI, 0.986 - 1.00) whereas microalbumin showed 0.944 (95 % CI, 0.907 - 0.981). Serum cystatin C showed a sensitivity of 96.7 % and a specificity of 91.7 % at a cutoff point of 1.34 mg / L whereas at a cut-off point of 138.5 mg / L for microalbumin, the sensitivity and specificity were 90 % and 83.3 % respectively. CONCLUSIONS Serum cystatin C and microalbumin both could be considered as markers for early detection of nephropathy in T2DM patients. The more prominent rise in serum cystatin C values provide an earlier diagnosis of diabetic nephropathy among T2DM patients. KEY WORDS Biomarker, Type 2 Diabetes Mellitus, Cystatin C, Diabetic Nephropathy, Microalbumin


Background: Diabetic Peripheral neuropathy is one of the most common cardiovascular complications among diabetes mellitus patients and occurs in more than half of the population of diabetic patients world-wide. It is a common cause of foot ulcer, gangrene and amputation among diabetics. Thus, its prevention or early treatment can improve the quality of life of diabetic patients. In a bid to reduce it, various biochemical markers have been evaluated to enable early treatment and amelioration of diabetic neuropathy among diabetes mellitus patients. Aim: Evaluation of the diagnostic relevance of Cystatin-C versus Albumin-creatinine ratio in assessment of Peripheral neuropathy in diabetic type 2 subjects. Method: 102 type 2 DM subjects (66 females and 36 males) and 100 control subjects of same age range (40 – 80 years) were recruited for this study which includes 51 subjects with peripheral neuropathy and 51 subjects without peripheral neuropathy. Serum Cystatin-C, Microalbuminuria, Urine creatinine and HBA1c were analysed with standard methods. Results: Cystatin-C, Microalbuminuria, Albumin-creatinine ratio and Glycated haemoglobin were significantly elevated (P<0.05) in diabetic subjects compared to the control. Cystatin-C (ng/ml), microalbuminuria (mg/l), albumin creatinine ratio (mg/mmol) and HBA1c (%) is [105.52 ± 45.11; 90.07±20.29; 10.48 ± 4.82; 6.9±1.7] respectively. Microalbuminuria, albumin creatinine ratio showed significant increase (P<0.05) in subjects with peripheral neuropathy compared to those subjects without [92.11± 22.82; 35.70±16.35; 2.61±1.1; 6.38±1.79]. The ROC curve shows that Albumin-creatinine ratio showed significant (P<0.05) sensitivity to peripheral neuropathy [AUC=0.714] while Cystatin-C showed no significant (P<0.05) sensitivity to peripheral neuropathy complication [AUC=0.553]. Conclusion: Cystatin-C was found to be deranged in diabetics. However, Albumin-creatinine ratio showed more diagnostic sensitivity for peripheral neuropathy than Cystatin-C.


2010 ◽  
Vol 49 (178) ◽  
Author(s):  
P Jha ◽  
BKL Das ◽  
S Shrestha ◽  
S Majhi ◽  
L Chandra ◽  
...  

INTRODUCTION: Diabetic nephropathy is one of the major complications of Diabetes Mellitus characterized by persistent albuminuria, elevated arterial blood pressure, a relentless decline in glomerular filtration rate (GFR) and a high risk of cardiovascular morbidity and mortality. METHODS: In this study, urinary micro-albumin estimation was done in 177 diabetic patients. This study aims to ascertain association of glycemicstatus, lipid profile and proteinuria in Type 2 Diabetes Mellitus with nephropathy. RESULTS: Among 177 patients, 26 had frank proteinuria, 79 had micro-albuminuria and 72 were without proteinuria. Increased frequency ofproteinuria was seen in male than female. Micro-albuminuria and frank proteinuria was seen more in older age group. The multiple comparisons showed the significantly increased levels of urea, creatinine, fasting blood glucose in micro-albuminuria and overt proteinuria patients in comparison to without proteinuria. Glycated hemoglobin level was increased with the increasing age group particularly in overt proteinuric patients. CONCLUSIONS: The glycemic control, monitoring of lipid profile and early urinary protein estimation with better management may delay diabetic nephropathy or its further complications in diabetes mellitus.  KEYWORDS: diabetes mellitus, diabetic nephropathy, frank proteinuria, glycated hemoglobin, micro-albuminuria.


2021 ◽  
pp. 6-8
Author(s):  
Yash Salil Patel

Microvascular complications of Type 2 Diabetes Mellitus (T2DM), (retinopathy and nephropathy) have a similar etiopathogenetic mechanism besides genetic predisposition. Even though these two complications frequently co-exist, their frequency varies. The association of these two signicant complications and their coexistence needs a relook. To study prevalence of retinopathy and nephropathy in Type 2 diabetes mel Aim: litus. Comparison of diabetic retinopathy and nephropathy in Type 2 diabetes mellitus and its correlation of diabetic retinopathy and nephropathy with duration of illness and various risk factors that affects development, progression and severity of diabetic retinopathy and nephropathy. 100 diabetic patients were taken up for study for a period of one year meeti Methodology: ng the criteria for the present study. Detailed history was taken from patient and meticulous examination was done of all patients with special emphasis on renal and ophthalmic symptoms. Clinical data and investigation prole was tabulated. Statistical analysis was done. Among 100 patients, 22 had diabetic retinopathy. Among patients with diab Results & Conclusion: etic retinopathy, 68.18% patients had positive family history. Among 100 patients, 32 had diabetic nephropathy, mean FBS was 207 mg%, PPBS was 317.8 mg% and mean HbA was 9.2%. Among patients with diabetic retinopathy, mean FBS was 211 mg%, PPBS was 324.9 1c mg%, HbA was 9.5%. From this study it is found that diabetic nephropathy starts earlier than retinopathy. In this study 1c hypertension was found to accelerate progression into nephropathy and retinopathy.


2007 ◽  
Vol 13 (4) ◽  
pp. 391-397 ◽  
Author(s):  
N. Bavbek ◽  
A. Kargili ◽  
O. Kaftan ◽  
F. Karakurt ◽  
A. Kosar ◽  
...  

P-selectin, E-selectin, and mean platelet volume are markers associated with platelet reactivity that have been demonstrated to be increased in diabetes. We were particularly interested to see if there was a difference in mean platelet volume and selectins between diabetics and nondiabetics, and in diabetics with and without nephropathy, and whether there was a correlation between mean platelet volume and selectins. One hundred and fourteen diabetic patients and 31 healthy controls were investigated. Plasma levels of P-selectin and E-selectin were higher in the diabetic group than in controls ( P = .001 and P = .007, respectively) and in diabetic patients with proteinuria than in patients without proteinuria ( P = .002 and P = .004, respectively). Protein excretion was lower in patients with low mean platelet volume values ( P = .004). In conclusion, elevated platelet volume and high selectin values may play a role in the development of vasculopathies and complications in diabetes mellitus. Further studies are needed to prove these results.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Bancha Satirapoj ◽  
Kasemsan Aramsaowapak ◽  
Theerasak Tangwonglert ◽  
Ouppatham Supasyndh

Background.Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction.Methods.A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline.Results.Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64–0.79, for UANG of 0.71; 95% CI 0.63–0.79, for UNGAL of 0.64; 95% CI 0.56–0.72, and for UKIM-1 of 0.71; 95% CI 0.63–0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles.Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function.


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