Is Kidney Injury Molecule 1 a Valuable Tool for the Early Diagnosis of Contrast-Induced Nephropathy?

AIM/SCOPE: Contrast-induced nephropathy (CIN) is a common complication of diagnostic/therapeutic procedures. Serum creatinine levels are sensitive but often lead to diagnostic delays in acute kidney injury and potential misclassification of actual injury status. Kidney injury molecule (KIM-1) is a novel early marker of acute kidney injury. The aim of our study was to evaluate the KIM-1 levels in patients with CIN. We performed a single-center, nested case-control study. MATERIALS AND METHODS: Three thousand two hundred patients who had undergone coronary angiography were included in the study. Thirty-two patients were diagnosed with CIN. Twenty patients who had undergone coronary angiography but did not have CIN were evaluated as a control group (n = 20). The diagnosis of CIN was performed according to the KDIGO 2012 Acute Kidney Injury Guideline criteria. Urinary KIM-1 levels were measured by enzyme-linked immunosorbent assay before as well as on the 6th and 48th hours of contrast exposure. Serum creatinine levels were measured before as well as on the 24th and 48th hours after angiographic procedure. RESULTS: We demonstrated that KIM-1 levels increased in the patients with CIN significantly on the sixth hour when compared with the baseline (P < 0.01; median levels, 0.27 and 0.70 mg/dL) but not in the controls (P = 0.107). The precontrast and 48th-hour KIM-1 levels were median ones and were also significantly different (P = 0.001, the median levels were 0.27 and 0.60 mg/dL, respectively). CONCLUSIONS: Because creatinine is a sensitive but a late marker of CIN, KIM-1 may be used for early diagnosis and early initiation of treatment and may reduce risk for morbidity.

Association of Glomerular Filtration Rate with Inflammation in Polycystic Ovary Syndrome.

BACKGROUND: We aimed to estimate the glomerular filtration rate (GFR) in women with polycystic ovary syndrome (PCOS) and to determine the relationship between GFR with C-reactive protein (CRP) and uric acid. MATERIALS AND METHODS: In this cross-sectional study, one-hundred and forty PCOS women and 60 healthy subjects were evaluated. The study was carried out at Endocrinol- ogy Outpatient Clinic, Erzurum Training and Research Hospital, Erzurum, Turkey, from December 2010 to January 2011. GFRs were estimated by Modification of Diet in Renal Disease (MDRD) formula. CRP, urinary albumin excretion (UAE) and uric acid levels were also measured. RESULTS: GFRs were significantly higher in PCOS group than control (135.24 ± 25.62 vs. 114.92 ± 24.07 ml/min per 1.73 m(2)). CRP levels were significantly higher in PCOS patients (4.4 ± 3.4 vs. 2.12 ± 1.5 mg/l). The PCOS group had significantly higher serum uric acid levels (4.36 ± 1.3 mg/dl vs. 3.2 ± 0.73 mg/dl). There was also significantly higher proteinuria level in PCOS patients. CONCLUSION: Even though PCOS patients had higher GFR, serum uric acid and UAE val- ues than control patients, the renal function was within normal limits. Increased GFR in PCOS women positively correlates with elevated serum CRP and uric acid.

Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study.

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction-restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.

Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome.

BACKGROUND: Nesfatin-1 is a recently discovered neuropeptide derived from its precursor nucleobindin-2 (NUCB2) and has been implicated in the regulation of feeding and energy metabolism. It is located in the brain and also produced at the periphery and present in the plasma. However, its pathophysiological role in humans remains unknown. Polycystic ovary syndrome (PCOS) is commonly presented with obesity, insulin resistance, hyperandrogenemia and hirsutism. AIM: To characterize serum nesfatin-1 levels in PCOS women and determine association of nesfatin-1 with metabolic parameters. MATERIALS AND METHODS: It is a cross-sectional study of 55 PCOS and 28 healthy women matched in age, in a university hospital setting. Anthropometric, hormonal, metabolic parameters and nesfatin-1 blood levels were determined. RESULTS: Nesfatin-1 levels were significantly higher in PCOS group compared with the controls 371.43 ± 2.50 versus 275.55 ± 1.74 pg/mL. Multivariate logistic regression analysis that contains: nesfatin-1, body mass index and homeostasis model assessment index revealed significant correlation of nesfatin-1 with the existence of PCOS (p < 0.05). CONCLUSIONS: Higher nesfatin-1 levels in PCOS women compared to control group may suggest a possibility that nesfatin-1 may play some role in the PCOS.

Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity.

Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain and the presence of specific tender points. The prevalence of FM has been estimated at 2-7 % of the general global population. The presence of FM in several rheumatic diseases with a structural pathology has been reported as 11-30 %. The objectives of this study were to determine the prevalence of FM and to evaluate the possible relationship between FM existence and disease activity among rheumatic diseases. The study group included 835 patients--197 rheumatoid arthritis (RA), 67 systemic lupus erythematosus (SLE), 119 ankylosing spondylitis (AS), 238 osteoarthritis (OA), 14 familial Mediterranean fever (FMF), 53 Behçet's disease (BD), 71 gout, 25 Sjögren's syndrome (SS), 20 vasculitis, 29 polymyalgia rheumatica (PMR), and two polymyositis (PM)--with or without FM. Recorded information included age, gender, laboratory parameters, presence of fatigue, and disease activity indexes. The prevalence of FM in patients with rheumatologic diseases was found to be 6.6 % for RA, 13.4 % for SLE, 12.6 % for AS, 10.1 % for OA, 5.7 % for BD, 7.1 % for FMF, 12 % for SS, 25 % for vasculitis, 1.4 % for gout, and 6.9 % for PMR. One out of two patients with PM was diagnosed with FM. Some rheumatologic cases (AS, OA) with FM were observed mostly in female patients (p = 0.000). Also, there were significant correlations between disease activity indexes and Fibromyalgia Impact Questionnaire scores for most rheumatologic patients (RA, AS, OA, and BD) (p < 0.05; respectively, r = 0.6, 0.95, 0.887, and 1). Concomitant FM is a common clinical problem in rheumatologic diseases, and its recognition is important for the optimal management of these diseases. Increased pain, physical limitations, and fatigue may be interpreted as increased activity of these diseases, and a common treatment option is the prescription of higher doses of biologic agents or corticosteroids. Considerations of the FM component in the management of rheumatologic diseases increase the likelihood of the success of the treatment.

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients.

BACKGROUND: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. METHODS: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. RESULTS: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64 ± 21.8 vs. 78.48 ± 19.7 µg/mL, p < 0.001) and a positive correlation was detected between TAFI antigen level and erythrocyte sedimentation rate and C-reactive protein levels (r = 0.247, p = 0.029 and r = 0.252, p = 0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p = 0.04 and p = 0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p = 0.04 and p = 0.001, respectively). CONCLUSIONS: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.

Effect of ethinyl estradiol-cyproterone acetate treatment on asymmetric dimethyl-arginine levels in women with polycystic ovary syndrome.

PURPOSE: Our study was undertaken to evaluate the levels of asymmetric dimethyl-arginine (ADMA) in a group of patients affected with polycystic ovary syndrome (PCOS)--under ethinyl estradiol-cyproterone acetate treatment or not--as compared with a group of healthy controls. METHODS: Fifty-eight women with PCOS and 45 patients as control group were included in the study. The 58 women with PCOS were separated into two groups: Group A (n = 29) were treated with an oral contraceptive pill containing 0.035 mg of ethinyl estradiol (EE) and 2 mg of cyproterone acetate (CA) (Diane-35) for 6 months. Group B (n = 29) did not take any drug. Group C (n = 45) was healthy women as control group. Serum levels of ADMA, lipid and glucose metabolism parameters, hormone profile were measured on the sixth month of treatment. RESULTS: ADMA levels were similar in women with PCOS and controls, whereas ADMA levels significantly decreased after a period of 6 months treatment with EE + CA in women with PCOS. ADMA levels and insulin resistance were decreased with treatment. However, patients with PCOS had significantly higher total cholesterol and Low-density lipoprotein cholesterol (LDL-C) compared to controls, treatment with EE + CA did not provide any improvement on lipid parameters. CONCLUSION: Serum ADMA levels and insulin resistance were lower in PCOS group treated with EE + CA than control group.

Thrombopoietin and mean platelet volume in patients with ischemic stroke.

OBJECTIVE: The aim of this study was to evaluate mean platelet volume (MPV), thrombopoietin (TPO), and platelet levels in patients with ischemic stroke and compare this with healthy controls. METHODS: We prospectively studied 50 patients with ischemic stroke and compared them with 37 control participants who have evaluated in internal medicine polyclinic and had no history of cerebrovascular events. All patients were within 24 hours after stroke; MPV and TPO were measured on admission. RESULTS: Both TPO and MPV values were significantly higher in patients with stroke (P = .00; P = .001). CONCLUSION: Increased TPO levels may increase both platelet count and platelet size, resulting in more hemostatic tendency, which may contribute to the progression of ischemic stroke.

Relationship between some clinical situations, autoantibodies, and pseudothrombocytopenia.

The widespread usage of blood count autoanalyzers has led to a major improvement in cellular hematology because of quick and accurate results found in most instances. However, spurious test results also can be observed like pseudothrombocytopenia (PTCP). In our study, we aimed to evaluate the clinical and laboratory factors associated with PTCP. Forty-six patients with PTCP and 69 healthy volunteers were enrolled in the study. Sex distribution was similar between the groups. Hospitalization, infection, the use of low-molecular-weight heparin and pregnancy increased the incidence of PTCP. Atherosclerosis and some drugs such as warfarin and calcium channel blockers were associated with PTCP, but the coincidence was not statistically significant. Antinuclear antibody positivity was higher in PTCP group (18.8% vs 7.2%; P=0.033) but anticardiolipin positivity rates were similar when compared to controls. Pseudothrombocytopenia was frequently misdiagnosed, which led to inappropiate treatments. Therefore, this situation should be kept in mind.

Serum thrombopoietin levels in patients with non-alcoholic fatty liver disease.

OBJECTIVE: To observe thrombopoietin (TPO) levels in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: The study was performed between November 2010 and March 2011 at the Department of Internal Medicine, Faculty of Medicine, Fatih University, Ankara, Turkey. A total of 60 consecutive patients with ultrasound proven NAFLD (study group), and 28 healthy volunteers (control study) were included in the study. The patient group was divided into 3 subgroups according to the ultrasonographic images as follows: minimal, intermediate, and marked hepatosteatosis. The TPO levels of the patient subgroups were compared with the healthy controls. All the data were collected prospectively, and recorded in FUHIS data collecting system, which is produced by our data-knowledge team. Quantitative measurements of thrombopoietin level were carried out by using the Human Thrombopoietin Quantikine ELISA Kit (R&D Systems, Minneapolis, Minnesota, USA). RESULTS: Thrombopoietin levels were significantly increased in the patient subgroups compared with the controls. The TPO levels were also higher in the patient subgroup of grade 1-nonalcoholic fatty liver disease (grade 1- NAFLD) compared with the control group. CONCLUSION: The TPO increased in patients with NAFLD possibly as an acute phase reactant to decreased inflammation. In clinical practice, physicians should be alerted to increased TPO levels in patients.

Heparin platelet factor 4 antibody positivity in pseudothrombocytopenia.

Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.