Toll‐like receptor inflammatory cascade and the development of diabetic kidney disease in children and adolescents with type 1 diabetes

Author(s):  
Thamara R Melo ◽  
Karla S C Souza ◽  
Marcela A G Ururahy ◽  
Raul H Bortolin ◽  
João F Bezerra ◽  
...  
Author(s):  
Aydilek Dağdeviren Çakır ◽  
Seha Kamil Saygılı ◽  
Nur Canpolat ◽  
Dildar Konukoğlu ◽  
Hande Turan ◽  
...  

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.


Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2713-2723 ◽  
Author(s):  
F. Liu ◽  
H. Y. Chen ◽  
X. R. Huang ◽  
A. C. K. Chung ◽  
L. Zhou ◽  
...  

2018 ◽  
Vol 315 (5) ◽  
pp. F1484-F1492
Author(s):  
Helen C. Looker ◽  
Michael L. Merchant ◽  
Madhavi J. Rane ◽  
Robert G. Nelson ◽  
Paul L. Kimmel ◽  
...  

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.


2017 ◽  
Vol 13 (11) ◽  
pp. 712-720 ◽  
Author(s):  
Mia J. Smith ◽  
Kimber M. Simmons ◽  
John C. Cambier

Author(s):  
Hadj Kacem Faten ◽  
Khouloud Boujelben ◽  
Allymamod Bibi Twaheerah ◽  
Safi Wajdi ◽  
Mnif Fatma ◽  
...  

2017 ◽  
Vol 33 (7) ◽  
pp. 1189-1196 ◽  
Author(s):  
Petter Bjornstad ◽  
Laura Pyle ◽  
David Z I Cherney ◽  
Richard J Johnson ◽  
Rachel Sippl ◽  
...  

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