Urinary Hepcidin Research Articles

#1738 Renal endogenous hepcidin alleviates ferroptosis of collecting duct in ischemia/reperfusion induced AKI

Abstract Background and Aims Recent studies have demonstrated that urinary and serum hepcidin predicted the incidence of acute kidney injury (AKI) among critically ill patients. As an endogenous acute phase hormone, hepcidin is synthesized not only by the liver but also secreted by distal nephron. However, the autocrine impact of hepcidin secreted by distal nephron on collecting duct cells in AKI remains poorly understood. Method We determined the expression and location of hepcidin in murine kidney in different severity of bilateral ischemia/reperfusion (bIRI) induced AKI model with ischemic duration for 20 min and 32 min. The effect of renal endogenous hepcidin was explored in cultured M-1 (Murine Cortical collecting duct) exposed to hypoxia/reoxygenation (H/R), as well as in bIRI mice with collecting duct-specific overexpression of hepcidin. Transgenic mice were generated by genetic cross between Hepcidin floxed mice which knocked the gene fragment of CAG-LSL-mHamp-flag-WPRE-PolyA into H11 locus and Cdh16-cre mice. Mechanistically, RNA-seq was performed in M-1 cells under H/R condition. Results The expression of renal endogenous hepcidin was significantly elevated in bIRI32min mice compared to both bIRI20min and sham group, suggesting that augmented secretion of hepcidin was induced by more severe AKI. Interestingly, renal endogenous hepcidin was mainly localized to distal convoluted tubule and collecting tubule as indicated by its co-staining with AQP2 and Calbindin-D28k in the kidney. To investigate the role of hepcidin in collecting duct, M-1 cells were cultured under hypoxia condition. We observed remarkable ferroptosis in collecting duct cells other than apoptosis nor necroptosis. Subsequently, hepcidin knockdown further exacerbated ferroptosis under H/R condition, as evidenced by an upregulation of PTGS2 expression and downregulation of GXP4 expression, lower proportion of GSH/GSSG ratio as well as enhanced lipid peroxide accumulation and production of Fe2+. Then, RNA-seq data revealed that hepcidin knockdown promoted the enrichment of genes related to oxidative stress and glutathione metabolic pathway which may be responsible for the deterioration of ferroptosis. To investigate the role of hepcidin in vivo, bIRI induced AKI was established in Cdh16-cre+Hepcidinflox/+ mice. We observed remarkable overexpression of Hepcidin-Flag localized to collecting duct and interstium area. Impressively, Cdh16-cre+Hepcidinflox/+ mice showed ameliorated renal dysfunction adrenal tubule injury histologically. Ferroptosis of renal was alleviated in Cdh16-cre+Hepcidinflox/+ mice as confirmed by an upregulation of GPX4 expression and downregulation of PTGS2, ACSL4, FPN expression, higher proportion of GSH/GSSG ratio, as well as reduced lipid peroxide accumulation and production of Fe2+ by Lipofluo (lipid peroxides) and FerroOrange (Fe2+) staining on frozen section of kidney. Ferroptosis of the collecting duct was alleviated as indicated by downregulation of PTGS2 expression which co-staining with AQP2. To demonstrate the beneficial role of hepcidin, exogenous hepcidin was applied to bIRI induced AKI mice to strengthen the endogenous protective response. Conclusion Renal endogenous hepcidin is induced in the distal tubule and collecting duct after AKI as a protective response via alleviating ferroptosis of collecting duct. Hepcidin may represent a novel therapeutic approach to promote tubule repair by targeting ferroptosis for AKI.

Treatment of berberine alleviates diabetic nephropathy by reducing iron overload and inhibiting oxidative stress.

Diabetic nephropathy (DN) has become one of the major fatal factors in diabetic patients. The aim of this study was to elucidate the function and mechanism by which berberine exerts renoprotective effects in DN. In this work, we first demonstrated that urinary iron concentration, serum ferritin and hepcidin levels were increased and total antioxidant capacity was significantly decreased in DN rats, while these changes could be partially reversed by berberine treatment. Berberine treatment also alleviated DN-induced changes in the expression of proteins involved in iron transport or iron uptake. In addition, berberine treatment also partially blocked the expression of renal fibrosis markers induced by DN, including MMP2, MMP9, TIMP3, β-arrestin-1, and TGF-β1. In conclusion, the results of this study suggest that berberine may exert renoprotective effects by ameliorating iron overload and oxidative stress and reducing DN.

Quantitative demonstration of the existence of two isoforms of canine hepcidin in the serum & urine of dogs

Hepcidin-25 is the key peptide hormone controlling vertebrate iron metabolism. However, in the last twenty years there was some disagreement in the literature over the structure of this compound. The aim of this research was to study whether more than one isoform of canine hepcidin-25 exists. For the purpose of comparison serum concentrations of hepcidin-25 were determined in the samples of 47 dogs sick with acute/chronic inflammation too. The study demonstrated that two isoforms of canine hepcidin-25 exist. A statistical correlation may indicate that both molecules are synthesised by dogs together. No statistically significant correlations were found between the measured concentrations of the two canine hepcidin-25 isoforms and the measured serum iron parameters in the sampled dogs, irrespective of the measurements were made in serum or urine. The mean urinary total hepcidin-25/creatinine ratio in healthy dogs was 1.08 ± 0.10. The mean serum total hepcidin-25 concentration was 79.8 ± 4.9 ng/ml, about 65% of which was the 25β version. The presence of inflammation results in a statistically significant increase in the serum concentration of both hepcidin varieties. The role and fate of the two molecules may need to be researched further to provide better understanding of their relation.

Elevated Urinary Hepcidin Level and Hypoferremia in Infants with Febrile Urinary Tract Infection: A Prospective Cohort Study.

To evaluate the kinetics of serum and urinary hepcidin levels along with anemia-related parameters during the infection course of infants with febrile urinary tract infection (UTI), we enrolled febrile infants aged one to four months in this prospective study. Febrile patients with UTI were allocated into Escherichia coli (E. coli) or non-E. coli groups according to urine culture results. Septic workup, blood hepcidin, iron profile, urinalysis, and urinary hepcidin-creatinine ratio were collected upon admission and 3 days after antibiotic treatment. In total, 118 infants were included. On admission, the febrile UTI group showed a significant reduction in serum iron level and a significant elevation of urinary hepcidin-creatinine ratio compared to the febrile control counterpart. Moreover, urinary hepcidin-creatinine ratio had the highest odds ratio, 2.01, in logistics regression analysis. After 3 days of antibiotic treatment, hemoglobin and the urinary hepcidin-creatinine ratio were significantly decreased. Patients with an E. coli UTI had a significantly decreased urinary hepcidin-creatinine ratio after 3 days of antibiotics treatment, whereas the non-E. coli group showed insignificant changes. Our study suggested that the urinary hepcidin-creatinine ratio elevated during acute febrile urinary tract infection and significantly decreased after 3 days of antibiotics treatment, especially in E. coli UTI.

Myeloid Specific HO-1-SIRT1-p53 Nexus Protects Against Iron Induced Chronic Liver Injury in Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects ~100,000 Americans and millions of people worldwide. People with SCD experience multiple complications, including acute pain episodes, stroke, and organ damage, with a median life expectancy of 42-47 years in the United States. Red blood cell transfusions are an important therapeutic intervention in SCD, however, chronically transfused SCD patients develop severe iron overload in the liver, heart, spleen, and endocrine organs with increased expression of inflammatory markers. In addition, there is evidence of abnormal iron metabolism in SCD with prior studies showing a low urinary hepcidin level in children with SCD and highly variable levels in adults. Thus, hepatic iron homeostasis in SCD both at baseline and upon repeated blood transfusion remains incompletely understood. In this study we evaluated iron homeostasis in Townes sickle cell mice at baseline and upon iron overload by iron dextran administration. We also evaluated the potential contribution of hepatic macrophages in hepatic iron homeostasis. Townes mice exhibited significant iron accumulation in the liver at baseline. We found significant reduction of hepcidin and increase in ferroportin and ferritin levels in the liver of sickle mice at baseline. However, upon hepatic iron overload (which was generated by intraperitoneal injections of iron dextran (1 g/kg) once a week for upto 10 weeks) the hepcidin ferroportin homeostasis was impaired and we found reduction of ferroportin and ferritin and increase in hepcidin in the sickle mouse liver. Immunohistochemically we could see a significant enrichment of iron loaded macrophages in the liver of SCD mice at baseline. Clodronate liposome mediated depletion of hepatic kupffer cells caused significant liver injury, hepatocyte death, systemic and hepatic iron accumulation and mortality in the mouse liver at baseline suggesting a protective role of hepatic kupffer cells in iron homeostasis. Mechanistic analysis further revealed protective mechanism through myeloid specific heme oxygenase 1 (HO-1)-sirtuin -1 (SIRT1)-p53 signaling that can potentially alleviate iron induced chronic liver injury in the SCD mice. At baseline, HO1 generated by kupffer cells stimulated SIRT1 activation in SCD mouse hepatocytes. Furthermore, HO-1 and SIRT1 prevented iron-induced senescence and hepatocyte cell death via regulating P53 signaling. Clodronate liposome-mediated kupffer cell loss drastically lowered HO-1 expression, which in turn reduced SIRT1 in SCD liver and accelerated senescence and cell death. In line with this finding, we also detected elevated levels of SIRT-1 in SCD patients’ blood serum. Work is currently underway to understand how modulation of HO-1-SIRT1-p53 signaling pathway can be used as a therapeutic option to combat iron induced chronic liver injury.

Validity of serum and urinary hepcidin as biomarkers for late-onset sepsis in premature infants.

Background:Sepsis remains one of the leading causes of neonatal morbidity and mortality, particularly among premature infants. Blood culture is the ‘gold standard’ for the diagnosis of neonatal sepsis but is associated with several pitfalls.Aim of the work:We aim to evaluate the validity of measuring serum (S.Hep) and urinary hepcidin (U.Hep) concentrations as diagnostic biomarkers for late-onset sepsis (LOS) in preterm infants.Patients and Methods:The current case-control study included 73 cases of clinically and laboratory confirmed late-onset sepsis as the ‘case group’ and 50 nonseptic premature infants of comparable age and sex as the ‘control group’. S.Hep and U.Hep concentrations were evaluated at enrollment (acute sample) and after 1 week of treatment (convalescent sample).Results:Patients had a statistically significant higher concentration of both S.Hep and U.Hep as compared with nonseptic controls (p = 0.0001). Similarly, a significant reduction of both S.Hep and U.Hep was detected after 1 week of treatment (p = 0.001). A cut-off value of ⩾ 94.8 ng/ml of S.Hep and ⩾ 264 ng/mg of U.Hep/urinary creatinine showed high sensitivity, specificity, and positive predictive value in the diagnosis of neonatal LOS.Conclusions:Both S.Hep and U.Hep can function as promising accurate and rapid surrogate tests for the diagnosis of LOS. U.Hep measurement has the advantage of being noninvasive, with no hazards of phlebotomy, and is less variable throughout the day.

Urinary hepcidin levels in children with beta-thalassemia major on chelation therapy

Urinary hepcidin levels in children with beta-thalassemia major on chelation therapy

Do Extremely Low Gestational Age Neonates Regulate Iron Absorption via Hepcidin?

To evaluate whether extremely preterm infants regulate iron status via hepcidin. In this retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial, urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo. The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio [ZnPP/H]) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-276/7weeks gestation were analyzed. The median Uhep/UCr concentration was 0.3, 1.3, 0.4, and 0.1ng/mg at baseline, 2weeks, 4weeks, and 12weeks, respectively, in placebo-treated infants. The median Uhep/UCr value in Epo-treated infants were not significantly different, with the exception of the value at the 2-week time point (median Uhep/UCr, 0.1ng/mg; P<.001). A significant association was seen between Uhep/UCr and ferritin at 2weeks (r=0.63; P<.001) and at 4weeks (r=0.41; P=.01) and between Uhep/UCr and ZnPP/H at 2weeks (r=-0.49; P=.002). Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that extremely preterm neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in extremely preterm neonates, particularly those treated with Epo.

Role of Serum and Urinary Hepcidin in Young Females of Reproductive Age in North India.

Introduction Iron deficiency is one of the most common nutritional disorders in the world affecting young females of the reproductive age group. Indeed, an ideal screening test should be capable of identifying iron deficiency long before developing anemia. Henceforth, the present study was aimed to determine utility of hepcidin in iron deficiency and to see its correlation with different iron indices. Methods This cross-sectional study was conducted in the Department of Biochemistry, SGT Medical College Hospital and Research Institute, Budhera, Gurugram, Haryana, India. It included 200 nonpregnant female students aged between 18 and 25 years. Estimation of hepcidin was by enzyme-linked immunosorbent assay. Quantitative estimation of serum iron, total iron-binding capacity (TIBC), and transferrin saturation was done via semi-autoanalyzer. Statistical analysis was done using SPSS v22. Results The reference range of urinary hepcidin established in this study was 110 to 969 ng/mg creatinine (mean ± standard deviation 328.3 ± 195.07 ng/mg creatinine). Serum hepcidin and urinary hepcidin had a significant correlation with iron indices. Area under the curve of urinary hepcidin was obtained with best combination of diagnostic sensitivity (82.6%) and specificity (83.1%) at a cutoff value of > 15.7 ng/mL and ≤ 199 ng/mg, respectively. Conclusion Since ferritin, TIBC, transferrin saturation, and hepcidin each represent different aspects of iron metabolism, incorporating hepcidin in the present diagnostics and combined evaluation of these indices may accord enhanced clinical information. Hepcidin would help to stratify the vulnerable young healthy female population in early stages of iron deficiency and guide proper interventions to reduce morbidity.

Combination of hepcidin with neutrophil gelatinase-associated lipocalin for prediction of the development of sepsis-induced acute kidney injury

Background and aimsThe early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis. Materials and methodsA prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay. ResultsOf the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong’s test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong’s test). ConclusionSerum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings.

Prenatal alcohol-related alterations in maternal, placental, neonatal, and infant iron homeostasis

Prenatal alcohol exposure (PAE) is associated with postnatal iron deficiency (ID), which has been shown to exacerbate deficits in growth, cognition, and behavior seen in fetal alcohol spectrum disorders. However, the mechanisms underlying PAE-related ID remain unknown. We aimed to examine biochemical measures of iron homeostasis in the mother, placenta, neonate, and 6.5-month-old infant. In a prenatally recruited, prospective longitudinal birth cohort in South Africa, 206 gravidas (126 heavy drinkers and 80 controls) were interviewed regarding alcohol, cigarette, and drug use and diet at 3 prenatal visits. Hemoglobin, ferritin, and soluble transferrin receptor (sTfR) were assayed twice during pregnancy and urinary hepcidin:creatinine was assayed once. Infant ferritin and hemoglobin were measured at 2 weeks and 6.5 months and sTfR was measured at 6.5 months. Histopathological examinations were conducted on 125 placentas and iron transport assays (iron regulatory protein-2, transferrin receptor-1, divalent metal transporter-1, ferroportin-1, and iron concentrations) were conducted on 63. In multivariable regression models, prenatal drinking frequency (days/week) was related to higher maternal hepcidin and to sequestration of iron into storage at the expense of erythropoiesis in mothers and neonates, as evidenced by a lower hemoglobin (g/dL)-to-log(ferritin) (ug/L) ratio [mothers: raw regression coefficient (β) = -0.21 (95% CI: -0.35 to -0.07); neonates: β = -0.15 (95% CI: -0.24 to -0.06)]. Drinking frequency was also related to decreased placental ferroportin-1:transferrin receptor-1 (β = -0.57 for logged values; 95% CI: -1.03 to -0.10), indicating iron-restricted placental iron transport. At 6.5 months, drinking frequency was associated with lower hemoglobin (β = -0.18; 95% CI: -0.33 to -0.02), and increased prevalences of ID (β = 0.09; 95% CI: 0.02-0.17) and ID anemia (IDA) (β = 0.13; 95% CI: 0.04-0.23). In causal inference analyses, the PAE-related increase in IDA was partially mediated by decreased neonatal hemoglobin:log(ferritin), and the decrease in neonatal hemoglobin:log(ferritin) was partially mediated by decreased maternal hemoglobin:log(ferritin). In this study, greater PAE was associated with an unfavorable profile of maternal-fetal iron homeostasis, which may play mechanistic roles in PAE-related ID later in infancy.

Iron sucrose ('RBT-3') activates the hepatic and renal HAMP1 gene, evoking renal hepcidin loading and resistance to cisplatin nephrotoxicity.

Iron sucrose (FeS) administration induces a state of renal preconditioning, protecting against selected forms of acute kidney injury (AKI). Recent evidence suggests that recombinant hepcidin also mitigates acute renal damage. Hence the goals of this study were to determine whether a new proprietary FeS formulation ('RBT-3') can acutely activate the hepcidin (HAMP1) gene in humans, raising plasma and renal hepcidin concentrations; assess whether the kidney participates in this posited RBT-3-hepcidin generation response; test whether RBT-3 can mitigate a clinically relevant AKI model (experimental cisplatin toxicity) and explore whether mechanisms in addition to hepcidin generation are operative in RBT-3's cytoprotective effects. Healthy human volunteers (n = 9) and subjects with Stages 3-4 CKD (n = 9) received 120, 240 or 360 mg of RBT-3 (intravenously over 2 h). Plasma and urine samples were collected and assayed for hepcidin levels (0-72 h post-RBT-3 injection). In complementary mouse experiments, RBT-3 effects on hepatic versus renal hepcidin (HAMP1) messenger RNA (mRNA) and protein levels were compared. RBT-3's impact on the mouse Nrf2 pathway and on experimental cisplatin nephrotoxicity was assessed. Direct effects of exogenous hepcidin on in vivo and in vitro (HK-2 cells) cisplatin toxicity were also tested. RBT-3 induced rapid, dose-dependent and comparable plasma hepcidin increases in both healthy volunteers and chronic kidney disease subjects (∼15 times baseline within 24 h). Human kidney hepcidin exposure was confirmed by 4-fold urinary hepcidin increases. RBT-3 up-regulated mouse hepcidin mRNA, but much more so in kidney (>25 times) versus liver (∼2 times). RBT-3 also activated kidney Nrf2 [increased Nrf2 nuclear binding; increased Nrf2-responsive gene mRNAs: heme oxygenase-1, sulfiredoxin-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H quinone dehydrogenase 1]. RBT-3 preconditioning (18 h time lapse) markedly attenuated experimental cisplatin nephrotoxicity (∼50% blood urea nitrogen/creatinine decrements), in part by reducing renal cisplatin uptake by 40%. Exogenous hepcidin (without RBT-3) treatment conferred protection against mild in vivo (but not in vitro) cisplatin toxicity. RBT-3 acutely and dramatically up-regulates cytoprotective hepcidin production, increasing renal hepcidin levels. However, additional cytoprotective mechanisms are activated by RBT-3 (e.g. Nrf2 activation; reduced cisplatin uptake). Thus RBT-3-induced preconditioning likely confers renal resistance to cisplatin via an interplay of multiple cytoprotective activities.

Hepcidin Status at 2 Months in Infants Fed Breast Milk Compared with Formula

Introduction: The basis for the superior absorption of iron from breast milk compared with infant formulas is unclear. The hormone hepcidin downregulates dietary iron absorption. Hepcidin production increases with increased body iron status (reflected in serum ferritin levels). We hypothesized that serum hepcidin levels are suppressed relative to iron status in infants fed breast milk compared with formula. Methods: Subjects were healthy infants presenting for routine 2-month clinic visit and strictly fed either breast milk or standard infant formula. Urinary hepcidin and ferritin levels (reflective of serum levels) were analyzed and compared across the breast milk- and formula-fed groups. The relationship between urinary hepcidin and ferritin levels within each group was analyzed by linear regression. Results: Twenty-four subjects were enrolled in each group. The median urinary hepcidin level in the group fed breast milk was lower than in formula (130 vs. 359 ng hepcidin/mg creatinine, p < 0.05). However, the median ferritin levels were similar (2.1 vs. 1.9 ng/mL). Within each group, urinary hepcidin correlated with urinary ferritin (r = 0.5, p < 0.05 for each group); however, the slope of the regression line was lower in the group fed breast milk compared with formula (p < 0.005). Conclusion: Despite similar urinary ferritin levels, urinary hepcidin levels are lower at 2 months in infants fed breast milk compared with infants fed formula. Hepcidin levels correlate with iron status in each group; however, this relationship is relatively dampened in infants fed breast milk. We speculate that relatively lower infant hepcidin contributes to the superior efficiency of iron absorption from breast milk.

P0414URINARY HEPCIDIN AS A BIOMARKER OF NEPHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Abstract Background and Aims Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that is associated with poor prognosis. The current available urinary biomarkers are neither sensitive nor specific for diagnosing LN. This study was undertaken to investigate whether urinary hepcidin represents a marker of nephritis in SLE patients. Method A cross-sectional study was conducted with 3 study groups compromising 30 patients with biopsy proven LN, 30 patients with non-nephritis SLE and 20 healthy control. Spot urinary samples were collected from all participants and the levels of hepcidin in urine were measured by ELISA, 24 h urinary proteins, urinary and serum creatinine were measured. Results Urinary hepcidin was significantly higher in LN patients than in non-nephritis SLE and control (470, 258, 43.0 ng/mg creatinine respectively) (P &amp;lt; 0.001) as shown in figure 1. Urinary hepcidin was significantly correlated with serum creatinine (P 0.017) and 24 hours urinary proteins (P 0.003). ROC curve cut-off values of urinary hepcidin were 4.3000, Area under curve (AUC) of hepcidin was 0.553, with sensitivity (SN) of 63.3%, specificity (SP) of 60%, Positive predictive value (PPV) 70.4, negative predictive value (NPV) 52.2 in SLE patients as shown in table 1 and figure 2. Conclusion Although urinary hepcidin level was significantly higher in LN patients than in non-nephritis SLE and control, it failed to discriminate patients with LN from those without. Further studies are still needed before considering urinary hepcidin as a non-invasive diagnostic marker of LN.

Evaluation of Urinary Hepcidin as a Marker for the Early Diagnosis of Iron Deficiency Anemia in Children

Background: Iron deficiency is an essential element, because nearly all living organism urine hepcidin levels could potentially be used in the determination of iron requirements and be an accurate indicator of physiological IDA. Aim: The present study aimed to evaluate the role of urinary hepcidin as an early diagnostic marker of iron deficiency anemia in children. Methods: This study included 45 children. Their age ranged from 6 to 16 years with hemoglobin levels ≤ 11.5 gm/dL and ferritin levels ≤ 20 ng/mL. The diagnostic performance of urinary hepcidin was estimated by analyzing the receiver operating characteristic curve. Diagnostic cut-off point with a high predictive value for iron deficiency was selected. Results: This study showed no statistically significant difference between the two studied groups regarding to demographic data. There were decrease in serum iron, ferritin, hemoglobin and Red blood cells (RBCs) indices in patient than the control group. There was non-significant decrease in urinary hepcidin in the study group compared to control group. The sensitivity and specificity of urinary hepcidin in diagnoses of iron deficiency anemia was 57.8 and 62.2 respectively with positive predictive value (63.3) in our study. There was positive correlation between urinary hepcidin and mean corpuscular volume (MCV), (r = 0.221), (p = 0.036), with the cut of value Conclusion: We concluded that the decrease of urinary level of hepcidin was non-significant in iron deficiency anemia compare to control group and needed further researches.

Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney.

ABSTRACTIntroduction:Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK.Methods:Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA.Results:The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/ Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/ CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/ Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/ Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively).Conclusions:MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

Urine hepcidin and iron regulation in preterm infants

Urine hepcidin and iron regulation in preterm infants

Urine hepcidin and iron regulation in preterm infants

Background: Iron deficiency during critical windows of brain development leads to irreversible neurodevelopmental delays. To limit this risk, iron supplementation in preterm infants is recommended, however concern persists regarding the risk of pro-oxidant injury with supplementation. It is unclear whether extremely low gestational age newborns (ELGANs) are able to regulate their iron status through hepcidin, the primary regulator of iron status in adults. Objective: Assess the role of urine hepcidin (Uhep) as a regulator of iron status …

Serum and Urinary Hepcidin for Diagnosing Iron-deficiency Anemia in Under-5 Children.

Bone marrow iron estimation remains the gold standard for diagnosing iron-deficiency anemia (IDA); serum ferritin, total iron-binding capacity, and transferrin saturation are routinely used as surrogate markers of IDA. However, these tests are marred by problems like poor specificity and sensitivity. Recently, hepcidin, a protein hormone synthesized in the liver and excreted in urine, has been shown to be related to iron status. We estimated the serum and urinary hepcidin levels in healthy children 6 to 60 months of age with (n=30) and without IDA (n=30). The mean (SD) serum hepcidin levels in children with IDA were significantly lower than those in children without IDA (3.03 [1.06] vs. 4.78 [3.94] ng/mL; P=0.02). The mean (SD) urinary hepcidin levels were also significantly lower in children with IDA than those in children without IDA (2.29 [0.53] vs. 2.79 [0.75] ng/mL; P=0.004). Performance of urinary and serum hepcidin compared with serum ferritin (<12 µg/L) for diagnosing IDA in terms of area under the receiver operating characteristic curve was 0.704 (P=0.007) and 0.59 (P=0.22), respectively. Serum hepcidin is not useful for diagnosing IDA in under-5 children. In contrast, urinary hepcidin holds promise as a noninvasive diagnostic tool for IDA in under-5 children.

Hepcidin – Potential biomarker of contrast-induced acute kidney injury in patients undergoing percutaneous coronary interventions

PurposeContrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary interventions (PCI). In this study, we tested the hypothesis whether serum and urinary hepcidin could represent early biomarkers of CI-AKI in patients with normal serum creatinine undergoing PCI. In addition, we assessed serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, eGFR and serum creatinine in these patients. MethodsSerum and urinary hepcidin and NGAL, serum cystatin C, were evaluated before, and after 2, 4, 8, 24 and 48 h after PCI using commercially available kits. Serum creatinine was assessed before, 24 and 48 h after PCI. ResultsWe found a significant rise in serum hepcidin as early as after 4 and 8 h when compared to the baseline values. Serum NGAL increased after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. We found a significant fall in urinary hepcidin after 8 and 24 h after PCI. Serum cystatin C increased significantly 8 h after PCI, reaching peak 24 h after PCI and then decreased after 48 h. The prevalence of CI-AKI was 8%. Urine hepcidin was significantly lower 8 and 24 h after PCI in patients with CI-AKI, while serum and urine NGAL were significantly higher in patients with CI-AKI. ConclusionsOur findings suggest that serum hepcidin might be an early predictive biomarker of ruling out CI-AKI after PCI, thereby contributing to early patient risk stratification. However, our data needs to be validated in large cohorts with various stages of CKD.