Urinary Vitamin Research Articles

P.327: Urinary vitamin D binding protein (VDBP) as a biomarker in systemic lupus erythematosus patients with lupus nephritis and its relation to renal activity.

P.327: Urinary vitamin D binding protein (VDBP) as a biomarker in systemic lupus erythematosus patients with lupus nephritis and its relation to renal activity.

Urinary Vitamin D Binding Protein as a Biomarker to Assess Steroid Responsiveness in Childhood Idiopathic Nephrotic Syndrome

Urinary Vitamin D Binding Protein as a Biomarker to Assess Steroid Responsiveness in Childhood Idiopathic Nephrotic Syndrome

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes.

Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined. Our objective was to assess the association of uVDBP with longitudinal changes in kidney function. Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates. Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 μg/mmol, 2.63 μg/mmol, and 2.48 μg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (β = 30.67 and β = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Urinary Vitamin D Binding Protein Level in Egyptian Systemic Lupus Erythematosus Patients: A Potential Biomarker for Lupus Nephritis and its Association with Renal Activity

Urinary Vitamin D Binding Protein Level in Egyptian Systemic Lupus Erythematosus Patients: A Potential Biomarker for Lupus Nephritis and its Association with Renal Activity

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.

Effects of Daily Ingestion of Two SunGold Kiwifruit for 6 Weeks on Metabolic and Inflammatory Biomarkers: A Randomized, Cross-Over, Exploratory Intervention Study.

Kiwifruit contain many components, some considered beneficial, such as vitamins, phytochemicals and dietary fibre, and others potentially harmful, such as fructose and glucose in fruit sugars. In a 6-week, randomised, crossover study aimed at exploring the net effects of daily consumption of kiwifruit, 23 healthy participants consumed two Actinidia chinensis var. chinensis 'Zesy002' (marketed as Zespri™ SunGold™ Kiwifruit) per day as part of their customary diet (intervention) or without kiwifruit (control) as their customary diet for 6 weeks in a cross-over study. Anthropometric data, venous blood, and urine samples were collected at the start and end of the 6-week intervention and control periods for the measurement of physical changes, plasma glucose, insulin, glycated haemoglobin, short-chain fatty acids, blood lipids, uric acid, inflammatory biomarkers, and urinary ascorbic acid. Variables were measured between the start and finish of interventions, and between intervention and control periods. Food diaries were completed on the 3 days before blood sampling to estimate dietary ascorbic acid and dietary fibre intakes. Despite urinary vitamin C and food diaries indicating compliance, and good precision in measurements, there were no appreciable changes in biomarkers during the study, either within or between intervention and control periods, that would indicate a change in health status. Thus, the sizes of any effects of kiwifruit ingestion were too small to become significant under the test conditions used, indicating a high probability that daily ingestion of two SunGold kiwifruit is safe with respect to metabolic health.

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.

RENAL10: Urinary Vitamin D Binding Protein and Kidney Injury Molecule-1 May Predict the Risk of Acute Kidney Injury in Heart Failure Patients Undergoing CF-LVAD Implantation

Background: Renal dysfunction in advanced heart failure (HF) and durable mechanical circulatory support (MCS) is common and harmful, yet current tests are inaccurate and confounded by body composition, fluid status, and other factors. Newer biomarkers more directly reflecting specific aspects of renal health/function have been tested in other fields but have yet to be tested in this complex setting. Urine vitamin-D-binding protein (uVDBP) and urine kidney injury molecule-1 (uKIM-1) have been shown to identify and stage severity of parenchymal kidney injury in several settings. The purpose of our study is to explore the potential role of uVDBP and uKIM-1 as biomarkers of acute renal damage among HF patients receiving CF-LVAD support. Methods: Our cohort included 29 HF patients undergoing CF-LVAD implantation. Early morning voided urine was collected immediately pre-implantation. Measurements of uVDBP and uKIM-1 were performed with ELISA kits and data were normalized to urine creatinine (ng/mg Cr.). Relationships of uVDBP and uKIM-1 and important baseline clinical characteristics (presence of kidney dysfunction, defined as eGFR<60 ml/min/1.73m2, and hemodynamic instability, defined as INTERMACS 1/2) were assessed using the Wilcoxon test. Relationships of baseline uVDBP and uKIM-1 (log2 transformed) with risk of acute kidney Injury (AKI) developing within 90 days after CF-LVAD implant were assessed, using logistic regression with adjustment for baseline kidney function and for baseline hemodynamic stability. AKI was assessed using RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Results: The cohort (n=29), had mean (SD) age 58 (14) years, 17.2% were female, and destination therapy goal for 96.6%. Baseline kidney dysfunction and hemodynamic instability were present in 37.9% and 44.8% of patients respectively, and 44.8% had AKI within 90 days. Baseline uVDBP [median (IQR)] was 0.88 (0.20-2.3) ng/mg Cr., and baseline uKIM-1 [median (IQR)] was 0.013 (0.0032-0.042) ng/mg Cr. Baseline uVDBP was found to be significantly associated with baseline kidney risk category (p <0.001), with higher uVDBP associated with worse baseline kidney health/function risk (assessed by combination of baseline low kidney function and hemodynamic instability, Fig.1A). Baseline uKIM-1 was significantly associated with baseline kidney function but not with baseline kidney risk category (Fig.1B). Two-fold higher baseline uKIM-1 was associated with nearly two-fold increased odds of 90-day AKI (Table.1). Similar results were obtained for baseline uVDBP. Conclusions: We have demonstrated that both uVDBP and uKIM-1 may provide additional information about baseline kidney health beyond that provided by serum creatinine-based and hemodynamic instability-based measures, assessed by risk for adverse 90-day kidney outcomes. Further study in larger cohorts is needed. Table 1. - Association of baseline urine markers with post-implant AKI Odds ratios (95% confidence intervals) Unadjusted Model 1 Model 2 uKIM-1 Per two-fold greater uKIM-1 1.98 (1.28-3.71) 4.39 (1.79-22.2) 8.76 (2.03-311) uVDBP Per two-fold greater uVDBP 1.99 (1.27-3.68) 2.25 (1.23-4.90) 7.74 (2.07-296) Model 1 was adjusted for baseline kidney dysfunction;Model 2 was adjusted for baseline kidney dysfunction and baseline hemodynamic instability

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Characteristics of Vitamin C Renal Leak

BackgroundReduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C: a renal leak. We hypothesized that vitamin C renal leak may be associated with disease-mediated renal dysregulation, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. ObjectivesWe investigated the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal disease associated with renal tubular dysfunction and low plasma vitamin C concentrations. MethodsWe conducted a non-randomized cross-sectional cohort study of men aged 24–42 y, with Fabry disease (n = 34) and controls without acute or chronic disease (n = 33). To match anticipated plasma vitamin C concentrations, controls were placed on a low-vitamin C diet 3 wk before inpatient admission. To determine the primary outcome of vitamin C renal leak prevalence, subjects were fasted overnight, and matched urine and fasting plasma vitamin C measurements were obtained the following morning. Vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 μM. Exploratory outcomes assessed the association between renal leak and clinical parameters, and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. ResultsCompared with controls, the Fabry cohort had 16-fold higher odds of renal leak (6% vs. 52%; OR: 16; 95% CI: 3.30, 162; P < 0.001). Renal leak was associated with higher protein creatinine ratio (P < 0.01) and lower hemoglobin (P = 0.002), but not estimated glomerular filtration rate (P = 0.54). Renal leak, but not plasma vitamin C, was associated with a nonsynonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (OR: 15; 95% CI: 1.6, 777; P = 0.01). ConclusionsIncreased prevalence of renal leak in adult men with Fabry disease may result from dysregulated vitamin C renal physiology and is associated with abnormal clinical outcomes and genomic variation.

Excess Dietary Vitamin B-6 Alters Startle Behavior of Rats

Excessive intakes of vitamin B-6 can produce peripheral nervous system abnormalities, but few reports of central nervous system effects exist. We measured startle response, a central nervous system reflex, in rats fed excess pyridoxine to determine if subtle effects on central nervous system function could be detected. Female Long-Evans rats (218 g; n = 12) were fed either 1, 10, 100, 200 or 300 times the requirement of pyridoxine HCl (7 mg/kg) for 7 wk. Startle behavior was assessed weekly in chambers that allowed quantification of movement in response to stimuli. Food intake and body weights did not differ among groups (P > 0.1), and urinary vitamin B-6 excretion reflected intake (P < 0.001). Overt toxicity was not observed. There was a marginally significant effect of pyridoxine intake over time (P = 0.053) on the amplitude of response to a startling acoustic stimulus (117 dB, 40 ms) administered alone; the response appeared attenuated at the three highest pyridoxine concentrations. When the same stimulus was preceded by either a 70- or 75-dB prepulse (40 ms), responses of groups fed the two highest pyridoxine concentrations were significantly reduced relative to those fed the two lowest concentrations (P < 0.05). No effect of diet was seen with a startling tactile stimulus. Changes in central nervous system function were detected in rats fed excess vitamin B-6 using techniques of startle behavior measurement.

People with diabetes and hypovitaminosis C fail to conserve urinary vitamin C

BackgroundHypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak. MethodsRetrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women. ResultsStatistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c. ConclusionIn the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

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.

PSUN169 Vitamin C Renal Leak in Diabetes

Abstract Background People with diabetes have lower plasma vitamin C concentrations compared to nondiabetic individuals. The prevalence of urinary vitamin C loss, and its relationship to plasma vitamin C concentrations are unknown. Methods In this cross-sectional cohort study of 162 individuals; 82 with diabetes and 80 nondiabetic controls, we investigated the prevalence and clinical characteristics of vitamin C renal leak, using fasting plasma and matched 1h urine samples. Based on vitamin C renal threshold, vitamin C renal leak was defined as presence of vitamin C in urine with plasma concentrations less than the minimal elimination threshold (MET) of 43.2µM in women or 38.1µM in men. We also assessed group differences in mean plasma vitamin C concentrations and investigated the association between diabetes-related clinical variables and renal leak. Vitamin C in plasma and urine was measured using coulometric electrochemical detection with high performance liquid chromatography. Results When compared with nondiabetic controls, subjects with diabetes had significantly increased prevalence of vitamin C renal leak (8.8% vs 32.9%: OR5, p&amp;lt;0.001) and decreased plasma vitamin C concentrations (53.1µM vs 40.9µM, p&amp;lt;0.001). Higher fasting plasma glucose, glycosylated hemoglobin A1c, body mass index, micro/macro vascular complications and protein creatinine ratio were predictive of vitamin C renal leak. Conclusion Increased prevalence of vitamin C renal leak in diabetes is associated with reduced plasma vitamin C concentrations. Glycemic control, microvascular complications, obesity, and proteinuria were associated with renal leak. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure.

BackgroundRenal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF.Materials and MethodsPatients (71 [64–77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA.ResultsProteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values (P = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range (P < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF.ConclusionWe showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Factors of Vitamin C Renal Leak

ObjectivesReduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C excretion: a renal leak. We hypothesized that vitamin C renal leak may be the consequence of disease-mediated dysregulation affecting the renal tubules, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. The study objective was to investigate the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal storage disease associated with renal tubular dysfunction and low plasma vitamin C concentration.MethodsThis was a non-randomized cross-sectional cohort study of males with Fabry disease (n = 34) and healthy male controls (n = 33). To determine primary outcome of vitamin C renal leak, matched urine and fasting plasma vitamin C measurements were obtained following an overnight fast. Based on data from healthy men, vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 µM. Exploratory outcomes assessed the association between renal leak and clinical parameters; and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. Proof-of-concept studies were conducted using two mouse models.ResultsCompared with healthy men, Fabry cohort had 16-fold higher odds of renal leak (6% vs 52%: OR16, P < 0.001). Renal leak was associated with higher protein creatinine ratio (p = 0.01), lower hemoglobin (p = 0.002) and hematocrit (p = 0.008). Renal leak, but not plasma vitamin C, was associated with a non-synonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (p = 0.01 and p = 0.47 respectively). Using two mouse models, we recapitulated the relationships between renal leak, dysregulated vitamin C renal reabsorption and low plasma vitamin C concentrations.ConclusionsIncreased prevalence of vitamin C renal leak in Fabry disease may result from dysregulated vitamin C renal physiology, with significant clinical and genomic associations. Renal leak may be more sensitive than plasma vitamin C in evaluating genomic associations in small cohorts.Funding SourcesIntramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20,892–1372.

23,25-Dihydroxyvitamin D3 is liberated as a major vitamin D3 metabolite in human urine after treatment with β-glucuronidase: Quantitative comparison with 24,25-dihydroxyvitamin D3 by LC/MS/MS

The complete understanding of the excretion of surplus 25-hydroxyvitamin D3 [25(OH)D3] in humans remains to be accomplished. In our previous study, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] 24-glucuronide was identified as a major urinary vitamin D3 metabolite, while the glucuronide of 23,25-dihydroxyvitamin D3 [23,25(OH)2D3] is another metabolite of interest but has not been sufficiently evaluated. Although the quantitative analysis of 24,25(OH)2D3 liberated in urine by the treatment with β-glucuronidase (GUS) has been conducted, no information was provided about the amount of the glucuronidated 23,25(OH)2D3 in the urine. In this study, we first developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS)-based method for the simultaneous quantification of 23,25(OH)2D3 and 24,25(OH)2D3 liberated in urine by GUS. The analysis of the urine samples revealed that the amount of 23,25(OH)2D3 was almost as much as that of 24,25(OH)2D3, in contrast to the fact that the plasma concentration of 23,25(OH)2D3 was much lower than that of 24,25(OH)2D3. These results strongly suggested that 23,25(OH)2D3 is more susceptible to glucuronidation and more promptly excreted into urine than 24,25(OH)2D3. Furthermore, the amount ratios of 23,25(OH)2D3 to 24,25(OH)2D3 in the urine samples did not markedly vary during the day (morning/evening) and even by a week-long vitamin D3 supplementation (1000 IU/body/day). We concluded that the C-23 hydroxylation plays a crucial role in the urinary excretion of surplus 25(OH)D3.

Evaluation of stool and urine parameters correlation to CRP and D-dimer in COVID-19 infected adults and their contact children

Aim: Aim is to depict suggestive urine and stool parameters in asymptomatic suspected contact children living with COVID-19 infected adults. These parameters will facilitate identifying children who deserve the confirmatory diagnosis of COVID-19 by PCR test. Methods: Study was conducted in the National Hepatology and Tropical Medicine Research institute (NHTMRI) Cairo, Egypt. It included 66 mild COVID-19 adult patients (group1) and their 82 asymptomatic contact children (group 2). Results: In group 1, both C reactive protein (CRP) and D-dimer levels were significantly high. C reactive protein was significantly positively correlated with urinary microalbumin> 30, albumin/ creatinine ratio and urine pus >10 cells / HPF and significantly negatively correlated with vitamin C. D-dimer was significantly negatively correlated with vitamin C. In group 2, CRP and D-dimer were significantly negatively correlated with urine specific gravity (SG), urinary vitamin C. CRP was significantly negatively correlated with stool pus > 10 cells/ HPF, while D-dimer was significantly positively correlated with stool occult blood. Receiver Operating Curve (ROC) analysis revealed that urine SG showed the highest area under the curve (AUC); 0.859, 0.96, sensitivity of 100%, 100% and specificity of 71.8%, 77.8% with reference to D-dimer and CRP; respectively. Conclusions: In contact children of adult COVID-19 proved infection, urine SG, stool occult blood and stool pus > 10 cells/ HPF can be feasible tool for suspected COVID-19 infection, based on its results COVID-19 PCR request can be an imperative option to confirm the diagnosis; particularly in developing countries where detection of COVID -19 by PCR is not readily feasible.

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.

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.