Urinary Vitamin D-binding Protein Research Articles

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene.

Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele. A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups. Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035). Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Performance of urinary vitamin D-binding protein in diabetic kidney disease: a meta-analysis

Objective To systematically evaluate the correlation between urinary vitamin D-binding protein (VDBP) and diabetic kidney disease and to evaluate the relationship between urinary VDBP and the albumin-to-creatinine ratio (ACR), renal function indicators [estimate glomerular filtration rate (eGFR), creatinine (CR), blood urea nitrogen (BUN)] and glycaemic control indices [glycated hemoglobin (HbA1c), fasting plasma glucose (FPG)]. Methods We searched the CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase and Web of Science databases up to May 31, 2023, for relevant literature. RevMan 5.3 software was used for the meta-analysis. Results Ultimately, 9 articles were included. Due to heterogeneity in the pooled results, the random-effects model was chosen. Meta-analysis results showed that the urinary VDBP concentrations in the normal albuminuria diabetes group were significantly higher than those in the healthy control group [SMD 1.52, 95% CI (0.84, 2.19), p < 0.00001]. The urinary VDBP concentrations in the microalbuminuria diabetes group were significantly higher than those in the normal albuminuria diabetes group [SMD 1.81, 95% CI (1.40, 2.21), p < 0.00001]. The urinary VDBP concentrations in the macroalbuminuria diabetes group were also significantly higher than those in the microalbuminuria diabetes group [SMD 1.51, 95% CI (1.05, 1.96), p < 0.00001]. In addition, urinary VDBP was positively correlated with the ACR, CR, BUN and HbA1c [Summary r = 0.73, 95% CI (0.54, 0.85), p < 0.0001; Summary r = 0.38, 95% CI (0.10, 0.61), p = 0.009; Summary r = 0.37, 95% CI (0.16, 0.55), p = 0.0008; Summary r = 0.40, 95% CI (0.13, 0.62), p = 0.005, respectively] and tended to be negatively correlated with the eGFR [Summary r = −0.64, 95% CI (−0.92, 0.10), p = 0.08] but was not significantly correlated with the FPG [Summary r = 0.16, 95% CI (−0.03, 0.33), p = 0.10]. Sensitivity analysis showed that our pooled results are robust. Conclusion Urinary VDBP may be used as a novel biomarker for the early diagnosis of DKD and can be used to assess the severity of DKD.

Correlation between urine vitamin D-binding protein and early-stage renal damage in Type 2 diabetes.

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. 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. 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. The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.

Does Urinary Vitamin D-Binding Protein Have a Role in the Prediction of Steroid Resistance in Nephrotic Syndrome? A Cohort Study on Egyptian Children

Background: Nephrotic syndrome (NS) is a common glomerular disease in children, for which there are currently no noninvasive markers for predicting responsiveness to steroid treatment. Objectives: This study aimed to analyze the relationship between clinical-laboratory presentations and subsequent response to steroid therapy and to evaluate the role of urinary vitamin D binding protein (uVDBP) as a predictor of steroid resistance (SR). Methods: This was a prospective longitudinal study on 60 children with active NS (30 patients with newly diagnosed NS and 30 with relapsed NS). In addition, 30 control subjects served as a reference group for uVDBP values. The patients were evaluated before starting steroid therapy, and response to steroid therapy was monitored 4 - 8 weeks later. Results: The levels of uVDBP were elevated in patients with NS (33.33 ± 15.6 ng/mL) compared to control subjects (17.35 ± 5.5 ng/mL, P &lt; 0.001). Also, the levels of uVDBP were significantly higher in patients with relapsed NS (37.93 ± 16.2 ng/mL) than in newly diagnosed NS patients (28.73 ± 13.67 ng/mL, P = 0.014). The level of uVDBP on presentation did not significantly differ between patients who had steroid-sensitive nephrotic syndrome (SSNS) (34.91 ± 15.01 ng/mL) and patients who had steroid-resistant nephrotic syndrome (SRNS) after 4 - 8 weeks of steroid treatment (32.60 ± 15.94 ng/mL, P = 0.417). Steroid resistance was significantly associated with a younger age of onset, specifically below 2.1 years (P = 0.023), a longer duration of the illness (P = 0.007), having more relapses (P = 0.002), total leucocytic count on presentation &gt; 8.05 × 103/mm3 (P = 0.031), and platelet counts on presentation &gt; 516.5 × 103/mm3 (P = 0.044). Conclusions: In this study, we found that uVDBP levels could reflect disease severity rather than predict the pattern of steroid responsiveness. Younger age of onset, longer duration of illness, previous relapses, and increased total leukocyte and platelet counts on presentation were associated with SRNS.

Urinary Biomarkers for Detection of Clinical Endometriosis or Adenomyosis.

Endometriosis or adenomyosis can be clinically diagnosed by ultrasound, symptoms, physical examination, and serum CA125. The urinary markers need to be investigated. The aim of our study was to investigate the urinary markers of clinical endometriosis/adenomyosis, and the correlation of serum CA125 was also studied. From the literature, alpha-1 antitrypsin (A1AT), enolase-1, vitamin D binding protein (VDBP), and CA125 in urine and serum were used in our study and measured by enzyme-linked immunosorbent assays (ELISA). Further clinical correlation and detection performance were evaluated. We enrolled 19 normal controls and 33 patients clinically diagnosed with endometriosis/adenomyosis. There were significant differences between studied patients and normal controls, as follows: serum CA125 (130.91 vs. 19.75 U/mL, p = 0.004); urinary CA125-creatinine ratio (5.591 vs. 0.254 ng/mg, p = 0.028); and urinary VDBP-creatinine ratio (28.028 vs. 7.301 ng/mg, p = 0.018). For diagnostic performances, serum CA125 provided the best results, with an area under curve (AUC) of 0.888 (p = 0.001) and accuracy of 86.5%. Other excellent results were also found using urinary VDBP (AUC 0.841, p = 0.001) and A1AT (AUC 0.722, p = 0.011) creatinine ratio. Using three combined biomarkers, serum CA125, urinary VDBP, and A1AT creatinine ratio, provided good detection power (AUC 0.913, p = 0.001, sensitivity 90.9%, specificity 76.5%). Double urine markers used in combination with VDBP and A1AT creatinine ratio also provided good diagnostic performance (AUC 0.809, p = 0.001, sensitivity 81.8%, specificity 76.5%, accuracy 80%). Further development of non-invasive point-of-care tests using these biomarkers could be a fruitful future endeavor.

Urinary vitamin D-binding protein as a marker of ovarian reserve

BackgroundOvarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve.MethodsUrine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis.ResultsWhen Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS.ConclusionsUrinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.

Study of the Value of Urinary Vitamin D-Binding Protein as a Prognostic Biomarker in Cases of Childhood Idiopathic Nephrotic Syndrome and its Relation to Calcium /Phosphorus Metabolism.

Introduction: Nephrotic syndrome (NS) is a common chronic kidney disease in childhood and it is mostly idiopathic. Aim of the Study: To determine if uVDBP measurements can be used as a non-invasive prognostic biomarker in cases of childhood idiopathic NS and its relation to Ca/P metabolism. Methods: This prospective study was carried out on children who were newly diagnosed with idiopathic nephrotic syndrome presented to the pediatric nephrology unit, Ain Shams University hospitals during the period from November 2019 till May 2020. Results: The present study showed that levels of uVDBP were significantly higher in cases than in healthy control children. Conclusion: We can conclude that uVDBP measurements represent a non-invasive prognostic biomarker in cases of childhood idiopathic NS.

Diagnostic value of VDBP and miR-155-5p in diabetic nephropathy and the correlation with urinary microalbumin.

This study explored the diagnostic and therapeutic significance of vitamin D binding protein (VDBP) and miR-155-5p for diabetic nephropathy and the correlation with urinary microalbumin. A total of 145 patients with type 2 diabetes who attended the Hwamei hospital were selected as research objects and assigned to diabetic nephropathy group (DN group) and diabetes group according to whether they suffered from diabetic nephropathy (DN). The expression levels of urine VDBP and serum miR-155-5p in the two groups were detected, and the correlation between urinary microalbumin (mAlb), serum cystatin C (Cys C) and 24-h urinary protein was analyzed. The predictive value of single and joint detection of urinary VDBP and serum miR-155-5p for DN onset and poor prognosis was analyzed. In DN patients, urine VDBP and serum miR-155-5p were highly expressed, and urine VDBP, serum miR-155-5p and mAlb, Cys C and 24-h urine protein were positively correlated (P<0.05). Moreover, the joint detection of urine VDBP and serum miR-155-5p was more valuable in diagnosis and poor prognosis prediction of DN patients than its single detection. Urine VDBP and serum miR-155-5p have good diagnostic value for DN, but their joint diagnostic value is higher, and their expression levels are all related to mAlb of DN patients, which may be used as new biological indicators for diagnosis and disease assessment.

Evaluation of urinary vitamin D-binding protein in type 1 diabetic children

Objective The aim of the study was to measure the levels of vitamin D-binding protein (VDBP) and microalbumin in the urine of diabetic children (type 1) and to analyze the correlation of VDBP with other parameters. Background Elevated urinary vitamin D-binding protein (UVDBP) level in patients with diabetes indicates that renal tubular damage may be involved in early stages of the development of diabetic nephropathy (DN). Patients and methods A total of 20 type 1 diabetic patients and 20 healthy controls were subjected to full history taken, thorough clinical examination, and laboratory investigation, which included complete blood count, blood glucose profile, glycosylated hemoglobin, parameters of kidney function, liver function, measurement of microalbuminurea, and VDBP in urine by enzyme-linked immunosorbent assay. Results UVDBP level showed significant increases in type 1 diabetic patients with microalbuminuria and macroalbuminuria (mean: 562.990 ± 194.771) when compared with control group (mean: 172. 480 ± 41.856; P = 0.001). There was a positive correlation between UVDBP as a marker of DN and fasting blood glucose, 2-h postprandial blood glucose (2-h PP), glycosylated hemoglobin, duration of the disease, and albumin/creatinine ratio, but no significant correlation between UVDBP as a marker of DN and other laboratory data. Conclusion Our finding indicates that UVDBP level is a potential biomarker for early detection of DN.

Immature megalin expression in the preterm neonatal kidney is associated with urinary loss of vitamin carrier proteins.

Vitamin A and D deficiencies are common in preterm infants. Megalin is an endocytic receptor in the proximal tubule, which reabsorbs retinol-binding protein (RBP) and vitamin D-binding protein (VDBP). Although the proximal tubule is immature in preterm infants, little is known about megalin expression during kidney development. In this study, we establish the abundance of megalin in the developing human kidney and its relationship to the urinary excretion of vitamin carriers in preterm infants. We analyzed a postmortem group (20-40 weeks gestation), where we used morphometric means of measuring megalin and its ligands in kidney tissue and a living group of patients (28-40 weeks), where urinary RBP and VDBP were measured. The presence of megalin, RBP, and VDBP increased in the proximal tubule through gestation. At birth the urinary concentration of RBP and VDBP were higher in the 28-32 week group compared to the 38-40 week group and a significant inverse correlation of tissue megalin and urinary loss of RBP and VDBP existed. Preterm infants experience vitamin carrier protein losses, which are associated with decreased megalin expression. This developmental expression of megalin in the kidney has clinical implications in the prevention of vitamin deficiencies in preterm babies.

Urinary Vitamin-D Binding Protein as an Early Predictor of Diabetic Nephropathyin Type 1 and Type 2 Diabetes

Diabetic nephropathy (DN) is the most common microvascular complication that may lead to chronic renal failure in diabetic patients. Till now microalbuminuria, with its restrictions, is the early marker of DN, appeared after the disease exacerbation. Thus, new biomarkers are required to predict the early onset of DN before the appearance of microalbuminuria. The aim of this study is to investigate the possible use of uVDBP in the early prediction of DN. Fifty diabetic patients with DN and 40 diabetic patients without DN for both types of diabetes were enrolled in this study. All patients were tested for uACR, uVDBP (measured by ELISA), and blood HbA1c. The results demonstrated a highly significant elevation of uACR, HbA1c and uVDBP in diabetic patients with DN compared to those without DN. uVDBP exhibited a strong positive correlation with HbA1c and uACR in DN patients. ROC curve analysis showed a greater AUC (0.93), and cutoff value was &gt;152 ng/ml with 94% sensitivity and 82% specificity for early detection of DN. These findings suggesting the sensitive and potential role of uVDBP in the early prediction and diagnosis of DN in type 1 and type 2 diabetes.

Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population.

Introduction Studies have shown increased urine excretion of vitamin D-binding protein (VDBP) in patients with diabetic nephropathy (DN) resulting from postulated mechanisms linked to renal tubular damage. In this study, we evaluate the utility of VDBP clearance ratio as a novel determinant of glycemic status, DN, and other diabetes-associated complications. Methods Levels of vitamin D, HbA1c, serum, urine concentrations of VDBP, and creatinine were measured in 309 subjects. The ratio of urine microalbumin to creatinine was determined to categorize subjects as normoalbuminuric (NAO), microalbuminuric (MIA), and macroalbuminuric (MAA). The VDBP clearance ratio was calculated. Results Mean VDBP clearance ratios in NAO, MIA, and MAA were 0.7, 4, and 15, respectively. Significant positive correlations of VDBP clearance ratio were found with age, WC, SBP, DBP, TG, glucose, HbA1c, urine VDBP, urine microalbumin, and urine microalbumin/creatinine, and a significant negative correlation was found with the steady-state estimate of beta cell function (B%). Receiver operating curve (ROC) analyses of the use of VDBP clearance ratio for detection of albumin status shows a value of 0.81 for the area under the curve. Conclusions The strong associations of VDBP clearance ratio with glycemic control and diabetes-associated complications suggest that this index could play a wider role in detection and/or pathogenesis and complications of diabetes.

Assessment of Vitamin D-Binding Protein and Early Prediction of Nephropathy in Type 2 Saudi Diabetic Patients.

Early detection of diabetic nephropathy (DN) represents a great challenge in an attempt to reduce the burden of chronic kidney diseases in diabetic patients. This study aimed to investigate the potential early prediction role of urinary vitamin D-binding protein (uVDBP) for the diagnosis of DN and to examine the possible correlation to serum VDBP, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance in these patients. Serum and urine samples were obtained from 40 healthy volunteers and 120 patients with type 2 diabetes divided into 3 groups: normoalbuminuria, microalbuminuria, and macroalbuminuria (urinary albumin excretion rate < 30, 30–300, and >300 μg/mg, resp.); n = 40/group. Serum and urinary VDBP levels were quantified by ELISA. Insulin resistance has been assessed by homeostasis model assessment index (HOMAI). Correction for urine creatinine concentration was applied for urinary quantitative measurements. uVDBP levels were significantly elevated in micro- and macroalbuminuria patient groups compared with those of the normoalbuminuria patient group and controls (820.4 ± 402.8 and 1458.1 ± 210.0 compared with 193.1 ± 141.0 and 127.7 ± 21.9 ng/mg, resp.) (P < 0.001). There was significant correlation between serum and urinary levels of VDBP in total patient group. Receiver operating characteristic analysis of uVDBP levels showed optimum cut-off value of 216.0 ng/mg corresponding to 98.8% sensitivity and 80.0% specificity and an area under the curve of 0.973 to discriminate the normoalbuminuria from the microalbuminuria groups. In multivariate analysis, ordination plot showed obvious demarcation between the study groups caused by the higher levels of uVDBP and albumin/creatinine ratio among other variables. The study findings suggested a possible clinical application of uVDPB as an early and a good marker for the detection of early renal disease in type 2 DM Saudi patients. Large-scale validation studies are warranted to confirm the results before including uVDBP with the available list of other conventional biomarkers.

A lack of association between vitamin D-binding protein and 25-hydroxyvitamin D concentrations in pediatric type 1 diabetes without microalbuminuria.

PurposeVitamin D deficiency is reported to be more common in type 1 diabetes patients and might be associated with the increased urinary loss of vitamin D binding protein (VDBP) consequent to impaired 25-hydroxyvitamin D (25(OH)D) circulation. We aimed to evaluate the possible increased urinary loss of VDBP, a correlation between VDBP and circulating 25(OH)D level, and risk factors influencing low vitamin D level in pediatric type 1 diabetes patients without microalbuminuria.MethodsThis is a cross-sectional study of subjects who visited Seoul National University Children’s Hospital between January and March 2013. Forty-two type 1 diabetes patients and 29 healthy controls were included. Biochemical parameters including serum and urine VDBP concentrations were analyzed.ResultsThere was no significant difference in the frequency of vitamin D deficiency or serum 25(OH)D level between the 2 groups. The serum and urine VDBP concentrations did not show any difference between the 2 groups. Serum 25(OH) D level did not correlate with serum or urine VDBP. Multivariate regression analysis revealed that daylight outdoor hours (β=2.948, P=0.003) and vitamin D intake (β=2.865, P=0.003) affected the 25(OH)D level; the presence of type 1 diabetes or urinary VDBP excretion was not significant.ConclusionsIn pediatric type 1 diabetes patients, urinary VDBP excretion did not contribute to low serum 25(OH)D level in the setting of normoalbuminuria. The factors associated with 25(OH)D level during winter periods were daylight outdoor hours and vitamin D intake. Further studies including both micro- and macroalbuminuria patients with type 1 diabetes are warranted.

Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein, and retinol-binding protein as early biomarkers of chronic kidney disease in dogs.

Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein‐to‐creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS‐PAGE and western blotting to determine the expression of albumin, vitamin D‐binding protein (VDBP), retinol‐binding protein (RBP), and Tamm‐Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (n = 9); and dogs with CKD (n = 40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (P ≤ 0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (P ≤ 0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence.

Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive) and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant) require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS) from steroid-resistant nephrotic syndrome (SSNS). Using the terms “idiopathic nephrotic syndrome,” “children,” and “biomarkers” the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, β2-microglobulin, and N-acetyl-β-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-β-D glucosaminidase, urine vitamin D-binding protein and α1β-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-β-D glucosaminidase and β2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required to establish their usefulness as noninvasive predictors of disease response to immunosuppressive therapy.

A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome.

Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). Information gleaned from such a panel could yield more individualized treatment plans and prevent unnecessary steroid exposure in patients unlikely to respond. Urine was collected from 50 pediatric patients diagnosed with idiopathic NS at Cincinnati Children’s Hospital Medical Center. Isobaric tags for relative and absolute quantitation (iTRAQ) was used to discover 13 proteins that were differentially expressed in SSNS vs SRNS in a small 5 × 5 discovery cohort. Suitable assays were found for 9 of the 13 markers identified by iTRAQ and were used in a 25 SRNS × 25 SSNS validation cohort. Vitamin D–binding protein (VDBP), alpha-1 acid glycoprotein 1 (AGP1), alpha-1 acid glycoprotein 2 (AGP2), alpha-1-B glycoprotein (A1BG), fetuin-A, prealbumin, thyroxine-binding globulin and hemopexin, and alpha-2 macroglobulin were measured and combined with urine neutrophil gelatinase–associated lipocalin (NGAL), which had been previously shown to distinguish patients with SRNS. Urinary VDBP, prealbumin, NGAL, fetuin-A, and AGP2 were found to be significantly elevated in SRNS using univariate analysis, with area under the receiver operating characteristic curves (AUCs) ranging from 0.65 to 0.81. Multivariate analysis revealed a panel of all 10 markers that yielded an AUC of 0.92 for identification of SRNS. A subset of 5 markers (including VDBP, NGAL, fetuin-A, prealbumin, and AGP2) showed significant associations with SRNS and yielded an AUC of 0.85.

Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography

BackgroundVitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.MethodWe included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death).ResultsIncreased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.ConclusionsUrinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.

Urinary Vitamin D-Binding Protein as a Biomarker of Steroid-Resistant Nephrotic Syndrome.

BACKGROUNDIdiopathic nephrotic syndrome (NS) is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin D-binding protein (uVDBP) excretion. We tested the hypothesis that uVDBP represents a biomarker to differentiate steroid-resistant nephrotic syndrome (SRNS) from the more benign forms of steroid-sensitive nephrotic syndrome (SSNS).METHODSThis cross-sectional study included children with SRNS (n = 24), SSNS (n = 28), and normal controls (n = 5). Urine and clinical data were collected from patients. Measurements of uVDBP were performed with a commercially available ELISA kit and normalized to urine creatinine.RESULTSConcentrations of uVDBP were significantly higher (P < 0.001) in patients with SRNS (13,659 ng/mL, interquartile range [IQR] 477–22,979) than in patients with SSNS (94 ng/mL, IQR 53–202) and normal controls (23 ng/mL, IQR 22–99, P = 0.002). Significance did not change when the results were corrected for urine creatinine. uVDBP was significantly negatively correlated with estimated glomerular filtration rate (eGFR; R = −0.76, P = 0.03). However, uVDBP was still markedly elevated in patients with SRNS with eGFR >100 mL/minute/1.73 m2. There was a positive correlation between microalbuminuria (MALB/Cr) and uVDBP (R = 0.67, P < 0.001). However, uVDBP displayed a much higher discriminatory ability for distinguishing SRNS than MALB/Cr (area under the curve = 0.92 vs 0.67, respectively). An uVDBP cutoff of 362 ng/mL yielded the optimal sensitivity (80%) and specificity (83%) to distinguish SRNS from SSNS.CONCLUSIONSIn this preliminary study, uVDBP represents a noninvasive biomarker that could distinguish SRNS from the more benign SSNS with high discriminatory power.

Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p < 0.001) and microalbuminuric (p < 0.01) diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p < 0.001). Correlation study revealed that both uMCP-1 and uVDBP were significantly positively correlated to urinary albumin/creatinine ratio (r = 0.968, p < 0.001 and r = 0.973, p < 0.001, respectively), serum urea (r = 0.461, p = 0.001 and r = 0.456, p = 0.002, respectively), and serum creatinine (r = 0.475, p = 0.001 and r = 0.448, p = 0.004, respectively) and significantly inversely correlated to glomerular filtration rate (r = -0.983, p < 0.001 and r = -0.988, p < 0.001, respectively). Receiver operating characteristic (ROC) curve analysis of uMCP-1 and uVDBP levels for early diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.