1.Correlation between urine vitamin D -binding protein and early -stage renal damage in Type 2 diabetes.
Yuxi HUANG ; Sijie CHEN ; Qing DAI ; Hao ZHANG ; Yan LIU
Journal of Central South University(Medical Sciences) 2023;48(1):40-48
OBJECTIVES:
The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage.
METHODS:
A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR.
RESULTS:
Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage.
CONCLUSIONS
The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.
Humans
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Diabetes Mellitus, Type 2/complications*
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Creatinine
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Vitamin D-Binding Protein/urine*
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Lipocalin-2/urine*
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Kidney/metabolism*
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Glomerular Filtration Rate
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Biomarkers
2.Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats.
Hye Ryoun JANG ; Sejoong KIM ; Nam Ju HEO ; Jeong Hwan LEE ; Hyo Sang KIM ; Soren NIELSEN ; Un Sil JEON ; Yun Kyu OH ; Ki Young NA ; Kwon Wook JOO ; Jin Suk HAN
Journal of Korean Medical Science 2009;24(Suppl 1):S161-S169
TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague- Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin- D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.
Animals
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Biological Transport
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Calcium/urine
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Calcium Channels/chemistry
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Calcium-Binding Protein, Vitamin D-Dependent/*biosynthesis
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Hydrochlorothiazide/pharmacology
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Hypercalciuria/*therapy
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Male
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Models, Biological
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Rats
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Rats, Sprague-Dawley
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Sodium/*metabolism
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Sodium-Hydrogen Antiporter/chemistry
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Sodium-Potassium-Chloride Symporters/metabolism
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TRPV Cation Channels/*biosynthesis/chemistry
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Thiazides/*pharmacology