Urine soluble urokinase plasminogen activator receptor as a potential biomarker of lupus nephritis activity.

There is a lack of non-invasive biomarkers to identify lupus nephritis (LN). Soluble urokinase plasminogen activator receptor (suPAR) is a sensitive biomarker of ongoing inflammation and a potential marker of podocyte dysfunction. The aim of this study was to assess urine and plasma suPAR in LN. 14 systemic lupus erythematosus (SLE) patients with newly diagnosed LN, 8 active SLE patients (SLEDAI >8) without LN and 31 healthy individuals were enrolled. Urine and plasma samples were taken before the initiation of LN induction therapy, and monthly thereafter. Global and renal disease activity were defined using the SLEDAI-2K and the SLEDAI-2K renal domain score, respectively. suPAR concentrations were measured with the suPARnostic Flex ELISA assay. Urine and plasma suPAR levels were elevated in SLE patients with active LN compared with resolved LN and healthy controls. Urine suPAR levels were comparable to healthy controls in active SLE without LN. Urine and plasma suPAR levels were higher before than after the initiation of LN induction therapy. Prospective follow-up measurements also suggested that urine suPAR levels raised again in patients with a relapse of LN according to SLEDAI-2K renal domain score, whereas plasma suPAR levels did not correlate with renal disease activity. Urine suPAR is a promising LN activity biomarker, given its isolated elevation in urine in active LN and pronounced decrease with LN improvement.

Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade.

BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS: There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 ± 4.70 µg/mL at baseline and 5.69 ± 4.94 µg/mL at week 16 (P = .71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade. CONCLUSIONS: We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.

The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive immune-mediated inflammatory disease, driven primarily by Th1 and Th17 cells. Anti-TNF therapies are successfully used in AS to achieve and maintain remission. However, their influence on the composition of T-cell subsets is not clear. We aimed to characterize the changes in the T-cell repertoire after a long-term anti-TNF treatment in AS patients. METHODS: Twenty-two AS patients under long-term anti-TNF therapy were evaluated (15 anti-TNF responders and 7 nonresponders). A wide range of cell subtypes was analyzed with flow cytometry and compared with therapy-naïve and short-term data too. RESULTS: Key findings include decreased proportions of naïve CD4 and CD8 cells, increased frequencies of Th1 and Th17 cells and higher Th1/Th2 ratios in the long-term anti-TNF-treated patients (responders, nonresponders and total), which was found to be significant not only when compared with healthy controls, but also with therapy-naïve and short-term anti-TNF-treated AS patients. We noted several alterations within the various activated T-cell subsets - increase in CD4HLADR cells in responders, in CD8HLADR cells in the whole AS group and in responders, and in CD4CD25 cells in responders, and decrease in CD4CD69 cell percentages in long-term treated patients - becoming evident only after long-term anti-TNF therapy. CONCLUSIONS: This study provides a comprehensive assessment of the impact of anti-TNF therapy on the T-cell repertoire in AS. Changes in T-cell phenotype seem to develop progressively during therapy, even in inactive disease, and reflect an ongoing effector T-cell differentiation and activation, along with the parallel compensatory increase in regulatory T cells.

Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

BACKGROUND: Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. METHODS: One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). RESULTS: Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 µg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). CONCLUSIONS: ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy.

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.

Circulating periostin level in asthmatic pregnancy.

OBJECTIVE: Asthma often complicates pregnancy and represents a risk for complications. Periostin is considered as a biomarker of asthma; however, as it also plays a role in normal gestation, pregnancy may influence circulating periostin levels. This is the first study assessing periostin in asthmatic pregnancy. METHODS: Plasma periostin levels were investigated in asthma (asthmatic non-pregnant, ANP; N = 19) and asthmatic pregnancy (AP; N = 14), compared to healthy non-pregnant controls (HNP; N = 12) and healthy pregnant women (HP; N = 17). The relationship between periostin levels and asthma control determinants was also evaluated. The diagnostic efficacy of periostin to detect uncontrolled asthma was analyzed using ROC analysis. RESULTS: Plasma periostin levels were similar in the HNP and ANP (55.68 [37.21-67.20] vs. 45.25 [32.67-64.55], p > 0.05), and elevated in the HP (68.81 [57.34-98.84] ng/mL, p = 0.02 vs. HNP) and AP groups (54.02 [44.30-74.94] ng/mL, p = 0.0346 vs. ANP). Periostin levels of the two pregnant groups were similar (p > 0.05). In AP women periostin correlated negatively with FEV1 (r = -0.5516) and positively with Raw (r = 0.5535; both p < 0.05). CONCLUSIONS: Pregnancy itself increases circulating periostin levels and this elevation is detectable in asthmatic pregnancy as well. Although periostin correlates with lung function in asthmatic pregnancy, periostin as a biomarker has to be handled with caution in pregnant patients due to the influence of pregnancy on its plasma level.

Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis.

BACKGROUND: Urokinase plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ-specific involvement. METHODS: suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling. RESULTS: suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g., Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis. CONCLUSIONS: Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity.

Lymphocyte subsets in pediatric migraine.

Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

Risk Estimation of Gestational Diabetes Mellitus in the First Trimester.

CONTEXT: There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications. OBJECTIVE: We aimed to identify early, first-trimester prediction markers for GDM. METHODS: The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later. RESULTS: Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR). CONCLUSION: Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.

Plasma soluble urokinase plasminogen activator receptor (suPAR) levels in systemic lupus erythematosus.

OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients. METHODS: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls. RESULTS: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70 ng/mL to distinguish patients with high disease activity (SLEDAI >8). CONCLUSION: suPAR might be an objective marker for identifying SLE patients with active disease.

Adaptive immunity in ankylosing spondylitis: phenotype and functional alterations of T-cells before and during infliximab therapy.

Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also tested short-term T-cell activation characteristics. Measurements were done in 13 AS patients before and during the intravenous therapy with anti-TNF agent infliximab (IFX). Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.

EDTA-Induced Pseudothrombocytopenia up to 9 Months after Initial COVID-19 Infection Associated with Persistent Anti-SARS-CoV-2 IgM/IgG Seropositivity.

Platelets have a role in vascular complications of COVID-19-related viral coagulopathy. Although immune-induced thrombocytopenia has been described mostly in moderate-to-severe COVID-19, the prognostic role of platelet count in COVID-19 is still controversial. Pseudothrombocytopenia has been reported to represent COVID-19-associated coagulopathy in critical illness, and transient EDTA-dependent pseudothrombocytopenia lasting less than 3 weeks was described in a patient with severe acute COVID-19 pneumonia. In our case study, EDTA-induced pseudothrombocytopenia was still present at 9 months after an initial SARS-CoV-2 virus infection in an apparently recovered 60 year old man. The persistence of antinucleocapside and antispike antibodies 9 months after the initial infection suggests that EDTA-induced pseudothrombocytopenia may be related to anti-SARS-CoV-2 IgG or IgM antibodies. We should acknowledge the possibility that pseudothrombocytopenia may also appear in some patients after seroconversion after the launch of large-scale vaccination programs.

Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury.

Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.

Soluble urokinase plasminogen activator receptor (suPAR) levels in healthy pregnancy and preeclampsia.

BACKGROUND: Preeclampsia is characterized by a maternal systemic inflammatory response and the impairment of maternal immune tolerance present in healthy pregnancy. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the monitoring of systemic inflammation. We aimed to assess the levels of suPAR and other markers of systemic inflammation in preeclampsia compared to healthy pregnancy. METHODS: We determined plasma suPAR, IL-6 and high sensitivity C-reactive protein (hs-CRP) levels in plasma samples of 62 healthy pregnant and 41 preeclamptic women in the third trimester of pregnancy. RESULTS: Plasma suPAR levels were elevated in preeclampsia [3.18 (2.30-4.71) ng/mL vs. 2.02 (1.81-2.40) ng/mL, p=0.0001, median (interquartile range)]. IL-6 and hs-CRP levels were also higher compared with healthy pregnancy [5.99 (2.97-18.12) pg/mL vs. 1.41 (1.00-2.70) pg/mL, p=0.0001 and 6.60 (3.55-15.40) mg/L vs. 3.90 (2.10-7.25) mg/L, p=0.006, respectively, median (interquartile range)]. Linear regression analyses revealed an association between individual plasma suPAR and log IL-6 levels as well as log hs-CRP levels. CONCLUSIONS: suPAR levels are elevated in preeclampsia and vary in a narrower range compared with IL-6 and hs-CRP. ROC analysis indicated that monitoring of suPAR levels is a suitable tool for the detection of systemic inflammation in pregnancy.

Immune phenotype of children with newly diagnosed and gluten-free diet-treated celiac disease.

BACKGROUND: Recent data suggest the involvement of both the adaptive and the innate immune system in celiac disease (CD). However, little is known about the immune phenotype of children with CD and its alteration upon dietary intervention. AIMS: We characterized the prevalence of major interacting members of the adaptive and innate immune system in peripheral blood of newly diagnosed children with CD and tested its alteration with the improvement of clinical signs after the introduction of gluten-free diet (GFD). METHODS: Peripheral blood was taken from ten children with biopsy-proven CD at the time of diagnosis and after the resolution of clinical symptoms following GFD. As controls, 15 children with functional abdominal pain were enrolled. The prevalence of the cells of adaptive and innate immunity was measured with labeled antibodies against surface markers and intracellular FoxP3 using a flow cytometer. RESULTS: Patients with CD were found to have lower T helper, Th1 and natural killer (NK), NKT and invariant NKT cell prevalence and with higher prevalence of activated CD4(+) cells, myeloid dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and monocytes compared to controls. After resolution of symptoms on GFD, the majority of these changes normalized, although the prevalence of NK and NKT cell, DC and TLR-2 expressing DCs and monocytes remained abnormal. CONCLUSIONS: The immune phenotype in childhood CD indicates the implication of both adaptive and innate immune system. The normalization of immune abnormalities occurs on GFD, but the kinetics of this process probably differs among different cell types.

Serum maternal hepcidin levels 3 days after delivery are higher compared to those measured at parturition.

AIM: Our aim was to investigate the levels of hepcidin at parturition and 3 days after delivery and to relate hepcidin levels to parameters of iron homeostasis. MATERIALS AND METHODS: We measured hepcidin levels with mass spectrometry in serum samples of 38 term pregnant women taken just prior to and 3 days after vaginal delivery (n = 23) or cesarean section (CS) (n = 15). Hepcidin levels were related to iron homeostasis parameters and interleukin (IL)-6 levels. Parameters measured before and after delivery were compared with the Wilcoxon test. RESULTS: Serum iron levels (median, interquartile range) decreased (14.3, 9.6-21.1 vs. 8.9, 6.8-11.5 µmol/L, P < 0.01), while hepcidin levels increased (2.73, 2.2-3.45 vs. 10.62, 6.70-15.89 µg/L, P < 0.01) by the third day after parturition compared to those measured before delivery. IL-6 levels were comparable before and after delivery. No direct association between serum hepcidin and iron homeostasis parameters or IL-6 levels was found. CONCLUSIONS: Factors triggering hepcidin synthesis dominate 3 days after delivery. Studies are needed to assess the contribution of hepcidin to iron homeostasis during the periparturition period.

Successful use of tocilizumab in a patient with rheumatoid arthritis following severe pancytopenia during etanercept therapy.

Severe cytopenia, including neutropenia and anemia, may occasionally occur during anti-tumor necrosis factor α (TNF-α) therapy. However, its mechanism is poorly understood, and little is known concerning the rationale of the choice of biologic therapy after a severe episode of cytopenia. The authors present the case of a 68-year-old rheumatoid arthritis patient in whom severe pancytopenia developed soon after the initiation of etanercept therapy. After resolution, the interleukin 6 receptor-blocking agent tocilizumab was introduced, which resulted in long-lasting complete remission of the rheumatoid arthritis without any adverse effects. The apoptosis-inducing effects of 3 TNF-α blockers and tocilizumab on peripheral blood mononuclear cells of the patient were compared by means of annexin V and propidium iodide labeling and flow cytometry. In concert with the clinical events, the anti-TNF-α agents demonstrated significantly higher apoptotic activities than that of tocilizumab. Tocilizumab appeared safe after anti-TNF-α-induced cytopenia possibly caused by apoptosis induction.

Regulatory T cells and T helper subsets in breast-fed infants with hematochezia caused by allergic colitis.

The objective of our study was to investigate the prevalence of CD4 T lymphocyte subsets and their commitment to TH1 or TH2 direction in 10 infants with allergic colitis (AC) and 10 healthy controls. Infants with AC presented with a higher ratio of naïve to memory cells, lower prevalence of activated CD4CD25 cells and FoxP3 regulatory cells, and a shift to TH2 direction in balance compared with controls. These alterations are normalized upon cessation of AC symptoms on elemental L-amino acid formula. These findings suggest the importance of antigen exposure in AC in infancy.

[Increased hepcidin levels three days after gynecological interventions]. / Emelkedett hepcidinszint nogyógyászati mutéteket követo harmadik napon.

UNLABELLED: Hepcidin is an endogenous substance that inhibits iron absorption and plasma iron levels. Due to technical reasons its levels are not routinely assessed and data regarding its clinical relevance are limited. We analyzed the alteration of hepcidin levels following gynecological interventions. Hepcidin levels were determined by mass spectrometry, along with the levels of interleukin-6, the main inductor of hepcidin with ELISA in 17 women undergoing gynecological intervention just prior to and three days after the surgery. The results were related to iron homeostasis parameters. A decrease in serum iron (median, interquartile range) (17.85 [15.25-24.9] versus 10.1 [7.6-15.0] µmol/l, p<0.01) and transferrin levels (60.3 [55.93-67.18] versus 53.1 [49.7-60.0], p< 0.01) µmol/l, simultaneously with an increase in hepcidin (2.75 [2.24-3.51] versus 8.01 [6.8-9.67] µg/l, p<0.01) and interleukin-6 levels (ND = not detected) (ND [ND - 2.2] versus 8.15 [2.31-12.86], p<0.01). CONCLUSION: As with other acute phase proteins postoperative hepcidin levels dramatically increase, simultaneously with other changes in iron homeostasis. These results indicate a possible causative relationship between increased hepcidin and decreased iron levels. In clinical practice, determination of hepcidin levels may be indicated for characterization and, possibly, prediction of postoperative iron homeostasis. However, measurement of hepcidin level in clinical practice is unlikely in the near future due to the lack of available kits for routine clinical laboratories.