Elevated Urinary VEGF-A,Transferrin, and Angiotensinogen Levels in Normoalbuminuric Children and Adolescents with Type 1 Diabetes; Can They Be Early Markers of Diabetic Kidney Disease?

2021 ◽  
Author(s):  
Aydilek Dağdeviren Çakır ◽  
Seha Kamil Saygılı ◽  
Nur Canpolat ◽  
Dildar Konukoğlu ◽  
Hande Turan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Children And Adolescents ◽  
Diabetic Kidney Disease ◽  
Disease Duration ◽  
Healthy Children ◽  
Diabetic Kidney ◽  
The Mean

Objective: We hypothesized that diabetic kidney disease (DKD) begins early, before albuminuria occurs. We therefore aimed to assess potential early urinary biomarkers of (DKD) in normoalbuminuric and normotensive children and adolescents with Type 1 Diabetes (T1D) to evaluate the relationship between these markers and clinical and laboratory risk factors for DKD. Methods: This cross-sectional study included 75 children and adolescents with T1D (62% females, mean age 13.9 ± 3.2 years) with normoalbuminuria [an albumin/creatinine ratio (ACR) below 30 mg/g creatinine]. Fifty-five age- and sex-matched healthy children and adolescents served as controls. For the assessment of early DKD, urinary levels of angiotensinogen (AGT), transferrin, nephrin, vascular endothelial growth factor-A (VEGF-A), and kidney injury molecule-1 (KIM-1) were measured in adequately collected 24-h urine samples using enzyme-linked immunoassays. Results: The mean disease duration was 7.3± 3.2 (ranged 2.1 - 15.7) years and the mean HbA1c level was 8.8±1.4%. The median levels of urine VEGF-A/Cr, AGT/Cr, and Transferrin/Cr were significantly higher in normoalbuminuric patients with T1D, compared with those of controls (p<0.001, p=0.02, and p=0.001, respectively), but there was no difference in nephrin/Cr and KIM-1/Cr between the two groups. Although, none of the patients had albuminuria, the median level of urine ACR was significantly higher in the patient group than the control group (p=0.003). The ACR was positively correlated with glomerular filtration rate (GFR). Urinary transferrin/Cr, AGT/Cr, and VEGF-A/Cr were significantly correlated with ACR, but not with either GFR or diabetic risk factors including HbA1c or disease duration. Conclusion: Normoalbuminuric and normotensive children and adolescents with T1D have elevated urinary VEGF, AGT and transferrin levels, which may indicate the development of DKD before albuminuria occurs.

scholarly journals Risk factors for diabetic kidney disease in adults with longstanding type 1 diabetes: results from the Canadian Study of Longevity in Diabetes

Renal Failure ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 427-433
Author(s):  
Nigar Sekercioglu ◽  
Leif Erik Lovblom ◽  
Petter Bjornstad ◽  
Julie A. Lovshin ◽  
Yuliya Lytvyn ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Canadian Study ◽  
Diabetic Kidney

scholarly journals A Machine Learning Approach to Predict 5-year Risk for Complications in Type 1 Diabetes

2021 ◽  
Author(s):  
Naba Al-Sari ◽  
Svetlana Kutuzova ◽  
Tommi Suvitaival ◽  
Peter Henriksen ◽  
Flemming Pociot ◽  
...  
Keyword(s):  
Machine Learning ◽  
Risk Factors ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Clinical Risk Factors ◽  
Diabetic Kidney ◽  
Clinical Risk

OBJECTIVE: Our aim was to apply state-of-the-art machine learning algorithms to predict the risk of future progression to diabetes complications, including diabetic kidney disease (≥30% decline in eGFR) and diabetic retinopathy (mild, moderate or severe). RESEARCH DESIGN AND METHODS: Using data in a cohort of 537 adults with type 1 diabetes we predicted diabetes complications emerging during a median follow-up of 5.4 years. Prediction models were computed first with clinical risk factors at baseline (17 measures) and then with clinical risk factors and blood-derived metabolomics and lipidomics data (965 molecular features) at baseline. Participants were first classified into two groups: type 1 diabetes stable (n=195) or type 1 diabetes with progression to diabetes complications (n=190). Furthermore, progression of diabetic kidney disease (≥30% decline in eGFR; n=79) and diabetic retinopathy (mild, moderate or severe; n=111) were predicted in two complication-specific models. Models were compared by 5-fold cross-validated area under the receiver operating characteristic (AUROC) curves. The Shapley additive explanations algorithm was used for feature selection and for interpreting the models. Accuracy, precision, recall, and F-score were used to evaluate clinical utility. RESULTS: During a median follow-up of 5.4 years, 79 (21 %) of the participants (mean+-SD: age 54.8 +- 13.7 years) progressed in diabetic kidney disease and 111 (29 %) of the participants progressed to diabetic retinopathy. The predictive models for diabetic kidney disease progression were highly accurate with clinical risk factors: the accuracy of 0.95 and AUROC of 0.92 (95% CI 0.857;0.995) was achieved, further improved to the accuracy of 0.98 and AUROC of 0.99 (95% CI 0.876;0.997) when omics-based predictors were included. The predictive panel composition was: albuminuria, retinopathy, estimated glomerular filtration rate, hemoglobin A1c, and six metabolites (five identified as ribitol, ribonic acid, myo-inositol, 2,4- and 3,4-dihydroxybutanoic acids). Models for diabetic retinopathy progression were less predictive with clinical risk predictors at, AUROC of 0.81 (95% CI 0.754;0.958) and with omics included at AUROC of 0.87 (95% CI 0.781;0.996) curve. The final retinopathy-panel included: hemoglobin A1c, albuminuria, mild degree of retinopathy, and seven metabolites, including one ceramide and the 3,4-dihydroxybutanoic acid). CONCLUSIONS: Here we demonstrate the application of machine learning to effectively predict five-year progression of complications, in particular diabetic kidney disease, using a panel of known clinical risk factors in combination with blood small molecules. Further replication of this machine learning tool in a real-world context or a clinical trial will facilitate its implementation in the clinic.

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
Sign in / Sign up

Export Citation Format

Share Document