scholarly journals Increased plasma kidney injury molecule-1 suggests early progressive renal decline in non-proteinuric patients with type 1 diabetes

2016 ◽  
Vol 89 (2) ◽  
pp. 459-467 ◽  
Author(s):  
Natalia Nowak ◽  
Jan Skupien ◽  
Monika A. Niewczas ◽  
Masayuki Yamanouchi ◽  
Melissa Major ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Injury ◽  
Kidney Injury Molecule 1

scholarly journals T Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes

2021 ◽  
Author(s):  
Josephine M. Forbes ◽  
Domenica A. McCarthy ◽  
Andrew J. Kassianos ◽  
Tracey Baskerville ◽  
Amelia J. Fotheringham ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
High Risk ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Glycemic Variability ◽  
Low Risk ◽  
Kidney Injury Molecule 1

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of kidney disease (DKD). In Type 1 diabetes, increased uACR (urinary albumin-creatinine ratio) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule- 1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. <p>DKD risk was assigned in youth with type 1 diabetes [n=100; 20.0±2.8 yrs; M:F-54:46, HbA<sub>1C</sub>-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m<sup>-2</sup>] and 10 year historical uACR, HbA<sub>1C</sub> and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to streptozotocin diabetes in <i>Apolipoprotein E-/-</i> mice. Kidney biopsies were used to examine infiltration of KIM-1 expressing T cells in DKD and compared with other chronic kidney disease.</p> <p>Individuals at high risk for DKD had persistent elevations in uACR (uACR<sub>AUC0-10yrs</sub>, 29.7±8.8 vs 4.5±0.5; <i>P</i><0.01 vs low risk) and early kidney dysfunction including ~8.3ml.min<sup>-1</sup>.1.73m<sup>-2</sup> higher estimated glomerular filtration rates (eGFR<sub>SCHWARTZ</sub>; <i>P<sub>adj</sub></i> <0.031 vs low risk) and plasma KIM-1 concentrations (~15% higher vs low risk;<i> P</i><0.034). High risk individuals had greater glycemic variability and increased peripheral blood T cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high risk youth with diabetes showed elevated collagen IV and SGLT2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T cell production of KIM-1.<b><br> </b></p>

scholarly journals Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase

2011 ◽  
Vol 79 (4) ◽  
pp. 464-470 ◽  
Author(s):  
Vishal S. Vaidya ◽  
Monika A. Niewczas ◽  
Linda H. Ficociello ◽  
Amanda C. Johnson ◽  
Fitz B. Collings ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Kidney Injury Molecule 1

scholarly journals T Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes

2021 ◽  
Author(s):  
Josephine M. Forbes ◽  
Domenica A. McCarthy ◽  
Andrew J. Kassianos ◽  
Tracey Baskerville ◽  
Amelia J. Fotheringham ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
High Risk ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Glycemic Variability ◽  
Low Risk ◽  
Kidney Injury Molecule 1

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of kidney disease (DKD). In Type 1 diabetes, increased uACR (urinary albumin-creatinine ratio) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule- 1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. <p>DKD risk was assigned in youth with type 1 diabetes [n=100; 20.0±2.8 yrs; M:F-54:46, HbA<sub>1C</sub>-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m<sup>-2</sup>] and 10 year historical uACR, HbA<sub>1C</sub> and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to streptozotocin diabetes in <i>Apolipoprotein E-/-</i> mice. Kidney biopsies were used to examine infiltration of KIM-1 expressing T cells in DKD and compared with other chronic kidney disease.</p> <p>Individuals at high risk for DKD had persistent elevations in uACR (uACR<sub>AUC0-10yrs</sub>, 29.7±8.8 vs 4.5±0.5; <i>P</i><0.01 vs low risk) and early kidney dysfunction including ~8.3ml.min<sup>-1</sup>.1.73m<sup>-2</sup> higher estimated glomerular filtration rates (eGFR<sub>SCHWARTZ</sub>; <i>P<sub>adj</sub></i> <0.031 vs low risk) and plasma KIM-1 concentrations (~15% higher vs low risk;<i> P</i><0.034). High risk individuals had greater glycemic variability and increased peripheral blood T cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high risk youth with diabetes showed elevated collagen IV and SGLT2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T cell production of KIM-1.<b><br> </b></p>

scholarly journals Kidney Injury Molecule-1 and the Loss of Kidney Function in Diabetic Nephropathy: A Likely Causal Link in Patients With Type 1 Diabetes

Diabetes Care ◽  
2015 ◽  
Vol 38 (6) ◽  
pp. 1130-1137 ◽  
Author(s):  
Nicolae M. Panduru ◽  
Niina Sandholm ◽  
Carol Forsblom ◽  
Markku Saraheimo ◽  
Emma H. Dahlström ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Function ◽  
Kidney Injury ◽  
Causal Link ◽  
Kidney Injury Molecule 1

scholarly journals LC-MS-based metabolomics analysis to identify meprin-β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury

2019 ◽  
Vol 317 (4) ◽  
pp. F1034-F1046 ◽  
Author(s):  
Jessica Gooding ◽  
Lei Cao ◽  
Faihaa Ahmed ◽  
Jean-Marie Mwiza ◽  
Mizpha Fernander ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Liquid Chromatography ◽  
Kidney Injury ◽  
Variable Importance ◽  
Proteolytic Processing ◽  
Indoxyl Sulfate ◽  
Pima Indians ◽  
Diabetic Kidney ◽  
Metabolomics Analysis

Meprin metalloproteases have been implicated in the pathophysiology of diabetic kidney disease (DKD). Single-nucleotide polymorphisms in the meprin-β gene have been associated with DKD in Pima Indians, a Native American ethnic group with an extremely high prevalence of DKD. In African American men with diabetes, urinary meprin excretion positively correlated with the severity of kidney injury. In mice, meprin activity decreased at the onset of diabetic kidney injury. Several studies have identified meprin targets in the kidney. However, it is not known how proteolytic processing of the targets by meprins impacts the metabolite milieu in kidneys. In the present study, global metabolomics analysis identified differentiating metabolites in kidney tissues from wild-type and meprin-β knockout mice with streptozotocin (STZ)-induced type 1 diabetes. Kidney tissues were harvested at 8 wk post-STZ and analyzed by hydrophilic interaction liquid chromatography ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Principal component analysis identified >200 peaks associated with diabetes. Meprin expression-associated metabolites with strong variable importance of projection scores were indoxyl sulfate, N-γ-l-glutamyl-l-aspartic acid, N-methyl-4-pyridone-3-carboxamide, inosine, and cis-5-decenedioic acid. N-methyl-4-pyridone-3-carboxamide has been previously implicated in kidney injury, and its isomers, 4-PY and 2-PY, are markers of peroxisome proliferation and inflammation that correlate with creatinine clearance and glucose tolerance. Meprin deficiency-associated differentiating metabolites with high variable importance of projection scores were cortisol, hydroxymethoxyphenylcarboxylic acid- O-sulfate, and isovaleryalanine. The data suggest that meprin-β activity enhances diabetic kidney injury in part by altering the metabolite balance in kidneys, favoring high levels of uremic toxins such as indoxyl sulfate and N-methyl-pyridone-carboxamide.

scholarly journals Serum Cystatin C as a Biomarker for Early Diabetic Nephropathy and Dyslipidemia in Young Type 1 Diabetes Patients

2020 ◽  
Author(s):  
Lina Radzeviciene ◽  
Ingrida Stankute ◽  
Ausra Monstaviciene ◽  
Rimantė Dobrovolskiene ◽  
Evalda Danyte ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Function ◽  
Cystatin C ◽  
Young Patients ◽  
Kidney Injury ◽  
Albumin Excretion Rate ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Long Term Follow Up

Abstract Background. Early capture of initial stages of complications is the destination of long term follow up of type 1 diabetes (T1D) patients. The aim of this study was to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients.Methods. 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results. Median age of study subjects was 16.2 years (2.1;26.4), diabetes duration – 5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c <7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine – 63 µmol/L (6;126). Median of eGFRcys was lower than eGFRcreat (92 ml/min/1.73m2 vs. 101 ml/min/1.73m2, p<0.001). 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r=-0.088, p<0.05, as well as cystatin C and HDL, r=-0.097, p<0.01.Conclusion. This study showed that cystatin C might be used as an additional biomarker of early kidney injury for young patients with T1D.

scholarly journals Consequences of Both Coxsackievirus B4 and Type 1 Diabetes on Female Non-Obese Diabetic Mouse Kidneys

2021 ◽  
Vol 9 (11) ◽  
pp. 2357
Author(s):  
Debra L. Walter ◽  
Jean R. Thuma ◽  
Ramiro Malgor ◽  
Frank L. Schwartz ◽  
Kelly D. McCall ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Disease Process ◽  
Kidney Injury ◽  
Nod Mice ◽  
The United States ◽  
Diabetic Mouse ◽  
Health Condition ◽  
Coxsackievirus B4

Despite the 2019 Executive Order on Advancing American Kidney Health Initiative, kidney disease has moved up in rank from the 9th to the 8th leading cause of death in the United States. A recent push in the field of nephrology has been to identify molecular markers and/or molecular profiles involved in kidney disease process or injury that can help identify the cause of injury and predict patient outcomes. While these studies have had moderate success, they have not yet considered that many of the health conditions that cause kidney disease (diabetes, hypertension, etc.) can also be caused by environmental factors (such as viruses), which in and of themselves can cause kidney disease. Thus, the goal of this study was to identify molecular and phenotypic profiles that can differentiate kidney injury caused by diabetes (a health condition resulting in kidney disease) and coxsackievirus B4 (CVB4) exposure (which can cause diabetes and/or kidney disease), both alone and together. Non-obese diabetic (NOD) mice were used for this study due to their susceptibility to both type 1 diabetes (T1D)- and CVB4-mediated kidney injury, in order to glean a better understanding of how hyperglycemia and viral exposure, when occurring on their own and in combination, may alter the kidneys’ molecular and phenotypic profiles. While no changes in kidney function were observed, molecular biomarkers of kidney injury were significantly up- and downregulated based on T1D and CVB4 exposure, both alone and together, but not in a predictable pattern. By combining individual biomarkers with function and phenotypic measurements (i.e., urinary albumin creatinine ratio, serum creatinine, kidney weight, and body weight), we were able to perform an unbiased separation of injury group based on the type of injury. This study provides evidence that unique kidney injury profiles within a kidney disease health condition are identifiable, and will help us to identify the causes of kidney injury in the future.

Association of Acute Kidney Injury During Diabetic Ketoacidosis With Risk of Microalbuminuria in Children With Type 1 Diabetes

2021 ◽  
Author(s):  
Jia Xin Huang ◽  
T. Charles Casper ◽  
Casey Pitts ◽  
Sage Myers ◽  
Lindsey Loomba ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Type 1 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Kidney Injury

scholarly journals Meprin Metalloprotease Deficiency Associated with Higher Mortality Rates and More Severe Diabetic Kidney Injury in Mice with STZ-Induced Type 1 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
John E. Bylander ◽  
Faihaa Ahmed ◽  
Sabena M. Conley ◽  
Jean-Marie Mwiza ◽  
Elimelda Moige Ongeri
Keyword(s):  
Type 1 Diabetes ◽  
Survival Rates ◽  
Kidney Injury ◽  
Diabetic Kidney ◽  
Nitrogen Levels ◽  
Protein Levels ◽  
Urine Albumin ◽  
Membrane Bound

Meprins are membrane-bound and secreted metalloproteinases consisting of α and/or β subunits that are highly expressed in kidney epithelial cells and are differentially expressed in podocytes and leukocytes (macrophages and monocytes). Several studies have implicated meprins in the progression of diabetic nephropathy (DN) and fibrosis-associated kidney disease. However, the mechanisms by which meprins modulate DN are not understood. To delineate the role of meprins in DN, we subjected meprin αβ knockout (αβKO) mice and their wild-type (WT) counterparts to streptozotocin-induced type 1 diabetes. The 18-week survival rates were significantly lower for diabetic meprin αβKO mice when compared to those for their WT counterparts. There were significant decreases in mRNA and protein levels for both meprin α and β in diabetic WT kidneys. Furthermore, the blood urea nitrogen levels and urine albumin/creatinine ratios increased in diabetic meprin αβKO but not in diabetic WT mice, indicating that meprins may be protective against diabetic kidney injury. The brush border membrane levels of villin, a meprin target, significantly decreased in diabetic WT but not in diabetic meprin αβKO kidneys. In contrast, isoform-specific increases in cytosolic levels of the catalytic subunit of PKA, another meprin target, were demonstrated for both WT and meprin αβKO kidneys.

Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis

2017 ◽  
Vol 171 (5) ◽  
pp. e170020 ◽  
Author(s):  
Brenden E. Hursh ◽  
Rebecca Ronsley ◽  
Nazrul Islam ◽  
Cherry Mammen ◽  
Constadina Panagiotopoulos
Keyword(s):  
Acute Kidney Injury ◽  
Type 1 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Kidney Injury
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