scholarly journals Role of Nox2 in diabetic kidney disease

2013 ◽  
Vol 304 (7) ◽  
pp. F840-F848 ◽  
Author(s):  
Young-Hyun You ◽  
Shinichi Okada ◽  
San Ly ◽  
Karin Jandeleit-Dahm ◽  
David Barit ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Macrophage Infiltration ◽  
Diabetic Kidney

NADPH oxidase (Nox) isoforms have been implicated in contributing to diabetic microvascular complications, but the functional role of individual isoforms in diabetic kidney are unclear. Nox2, in particular, is highly expressed in phagocytes and may play a key inflammatory role in diabetic kidney disease. To determine the role of Nox2, we evaluated kidney function and pathology in wild-type (WT; C57BL/6) and Nox2 knockout (KO) mice with type 1 diabetes. Diabetes was induced in male Nox2 KO and WT mice with a multiple low-dose streptozotocin protocol. Groups were studied for kidney disease after 8 and 20 wk of diabetes. Hyperglycemia and body weights were similar in WT and Nox2 KO diabetic mice. All functional and structural features of early and later stage diabetic kidney disease (albuminuria, mesangial matrix, tubulointerstitial disease, and gene expression of matrix and transforming growth factor-β) were similar in both diabetic groups compared with their respective nondiabetic groups, except for reduction of macrophage infiltration and monocyte chemoattractant protein-1 in the diabetic Nox2 KO mice. Systolic blood pressure by telemetry was surprisingly increased in Nox2 KO mice; however, the systolic blood pressure was reduced in the diabetic WT and Nox2 KO mice by tail-cuff. Interestingly, diabetic Nox2 KO mice had marked upregulation of renal Nox4 at both the glomerular and cortical levels. The present results demonstrate that lack of Nox2 does not protect against diabetic kidney disease in type 1 diabetes, despite a reduction in macrophage infiltration. The lack of renoprotection may be due to upregulation of renal Nox4.

scholarly journals Novel Biochemical Markers of Neurovascular Complications in Type 1 Diabetes Patients

2020 ◽  
Vol 9 (1) ◽  
pp. 198 ◽  
Author(s):  
Falkowski ◽  
Rogowicz-Frontczak ◽  
Szczepanek-Parulska ◽  
Krygier ◽  
Wrotkowska ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Peripheral Neuropathy ◽  
Kidney Disease ◽  
Biochemical Markers ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Multivariate Logistic Regression Analysis ◽  
Microvascular Damage ◽  
Diabetic Kidney

Type 1 diabetes mellitus (T1DM) is associated with chronic complications, which are the result of neurovascular changes. There is still a lack of universal biochemical markers of microvascular damage. The present study aimed to investigate whether selected inflammatory proteins are related to the prevalence of microvascular complications in adult T1DM patients. The following markers were determined in a group of 100 T1DM participants: epidermal growth factor (EGF), metalloproteinase 2 (MMP-2), growth/differentiation factor 15 (GDF-15), and interleukin 29 (IL-29). Screening for microvascular complications, such as autonomic and peripheral neuropathy, diabetic kidney disease, and retinopathy, was conducted. The group was divided according to the occurrence of microvascular complications. At least one complication was required for the patient to be included in the microangiopathy group. The median EGF concentration in the microangiopathy group was higher than in the group without microangiopathy (p = 0.03). Increasing EGF concentration was a statistically significant predictor of the presence of microangiopathy in multivariate logistic regression analysis (p < 0.0001). Additionally, a higher GDF-15 level was associated with diabetic kidney disease, peripheral neuropathy, and proliferative retinopathy vs. nonproliferative retinopathy. GDF-15 concentration correlated negatively with estimated glomerular filtration rate (eGFR) (r = −0.28; p = 0.02). To conclude, higher EGF concentration is an independent predictor of the presence of microvascular complications in T1DM patients. Besides the relation between GDF-15 and diabetic kidney disease, it may be also associated with peripheral neuropathy and retinopathy.

scholarly journals C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes

Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2713-2723 ◽  
Author(s):  
F. Liu ◽  
H. Y. Chen ◽  
X. R. Huang ◽  
A. C. K. Chung ◽  
L. Zhou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
C Reactive Protein ◽  
Diabetic Kidney ◽  
Reactive Protein

scholarly journals Urine inositol pentakisphosphate 2-kinase and changes in kidney structure in early diabetic kidney disease in type 1 diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. F1484-F1492
Author(s):  
Helen C. Looker ◽  
Michael L. Merchant ◽  
Madhavi J. Rane ◽  
Robert G. Nelson ◽  
Paul L. Kimmel ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Albumin Excretion Rate ◽  
Diabetes Duration ◽  
Limit Of Quantification ◽  
Diabetic Kidney ◽  
Kidney Structure

We examined the association of urine inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPP2K) with the presence and progression of diabetic kidney disease (DKD) lesions. Urine IPP2K was measured at baseline by quantitative liquid chromatography-mass spectrometry in 215 participants from the Renin-Angiotensin System Study who had type 1 diabetes and were normoalbuminuric and normotensive with normal or increased glomerular filtration rate (GFR). Urine IPP2K was detectable in 166 participants. Participants with IPP2K below the limit of quantification (LOQ) were assigned concentrations of LOQ/√2. All concentrations were then standardized to urine creatinine (Cr) concentration. Kidney morphometric data were available from biopsies at baseline and after 5 yr. Relationships of IPP2K/Cr with morphometric variables were assessed by linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, treatment assignment, and, for longitudinal analyses, baseline structure. Baseline mean age was 29.7 yr, mean diabetes duration 11.2 yr, median albumin excretion rate 5.0 μg/min, and mean iohexol GFR 129 ml·min−1·1.73m−2. Higher IPP2K/Cr was associated with higher baseline peripheral glomerular total filtration surface density [Sv(PGBM/glom), tertile 3 vs. tertile 1 β = 0.527, P = 0.011] and with greater preservation of Sv(PGBM/glom) after 5 yr ( tertile 3 vs. tertile 1 β = 0.317, P = 0.013). Smaller increases in mesangial fractional volume ( tertile 3 vs. tertile 1 β = −0.578, P = 0.018) were observed after 5 yr in men with higher urine IPP2K/Cr concentrations. Higher urine IPP2K/Cr is associated with less severe kidney lesions at baseline and with preservation of kidney structure over 5 yr in individuals with type 1 diabetes and no clinical evidence of DKD at baseline.

scholarly journals B cells in type 1 diabetes mellitus and diabetic kidney disease

2017 ◽  
Vol 13 (11) ◽  
pp. 712-720 ◽  
Author(s):  
Mia J. Smith ◽  
Kimber M. Simmons ◽  
John C. Cambier
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
B Cells ◽  
Kidney Disease ◽  
Type 1 Diabetes Mellitus ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney

scholarly journals Value of Intrarenal Artery Resistive Index for Detecting Diabetic Kidney Disease: A Cross-sectional Study

2021 ◽  
Author(s):  
Ferehiwot Bekele Getaneh ◽  
Yewondwossen Tadesse Mengistu ◽  
Daphne H. Knicely
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Linear Relationship ◽  
Multiple Regression ◽  
Diabetic Kidney Disease ◽  
Resistive Index ◽  
Diabetic Kidney ◽  
The Mean

Abstract Background: The typical pattern of diabetic kidney disease (DKD) which follows glomerular hyperfiltration progressing to persistent albuminuria associated with hypertension and declining glomerular filtration rate (GFR) has changed over the years. The aim of the study is to examine the potential role of Doppler ultrasound in early identification of DKD. Methods: A 137 patients with type 1 or type 2 diabetes mellitus (DM) patients in Ethiopia participated in the study. We analyzed the correlation between resistive index (RI) of intrarenal arteries and clinical characteristics, eGFR and 24-hr urine. We evaluated the linear relationship of RI with multiple variables using multiple regression analysis. Sensitivity, specificity and area under curve (AUC) of the receiver operating curve (ROC) were assessed.Results: Among the 137 participants, 48.9% were patients with type 1 DM and 51.1% with type 2 DM. Mean age ± SD was 42±15 years. The median 24-hr urine protein was 156 (IQR=149.5) mg/24hr. Mean eGFR was 104.26±17.25 (mL/min/1.73 m2). The mean RI was 0.7±0.06. The mean RI was significantly correlated with age and eGFR (r=0.64 & -0.56, P<0.001 respectively). Our multiple regression model relating mean RI to age, eGFR, systolic blood pressure (SBP), diastolic blood pressure (DBP), duration of diabetes and body mass index (BMI) was significant (overall F-test P-value<0.001). The AUC of the ROC curve of mean RI to identify a low eGFR was 0.82 (95% CI, 0.6 to 1). Sensitivity and specificity of 80% and 53% was calculated respectively.Conclusion: A significant linear relationship has been observed between RI and eGFR. This indicates RI values can determine the level of renal function loss with high accuracy.

Predictive factors associated with diabetic kidney disease in adult-onset Type 1 Diabetes

2021 ◽  
Author(s):  
Hadj Kacem Faten ◽  
Khouloud Boujelben ◽  
Allymamod Bibi Twaheerah ◽  
Safi Wajdi ◽  
Mnif Fatma ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Predictive Factors ◽  
Diabetic Kidney Disease ◽  
Adult Onset ◽  
Diabetic Kidney ◽  
Factors Associated ◽  
Onset Type
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