Circulating interferon-λ3 and post-vaccination antibodies against the surface antigen of hepatitis B virus in hemodialysis patients exposed to hepatitis E virus.

Responsiveness to the hepatitis B virus (HBV) vaccination in hemodialysis (HD) patients who had been exposed to the hepatitis E virus (HEV) and persistently generate antibodies against HEV remains unknown. Interferon (IFN)-λ3 positively correlates with the surface HBV antibodies (anti-HBs) in both healthy and HD subjects. We aimed to show whether HD patients differ in circulating IFN-λ3 and vaccine-induced anti-HBs titers concerning natural HEV immunization. HBV/HCV negative HD patients (31 HEV IgG positive, 45 HEV negative), HBV vaccinated and receiving booster doses as needed, had been tested for anti-HBs titers (CMIA) and IFN-λ3 concentrations (ELISA) in the blood collected before a dialysis session. There were no differences in circulating IFN-λ3 and anti-HBs titers between both groups. In responders to the HBV vaccine, there was a positive correlation between plasma IFN-λ3 levels and anti-HBs titers (r = 0.505, adjusted P = 0.01 in HEV exposed subjects; r = 0.523, adjusted P = 0.001 in controls). HEV past infection does not attenuate post-vaccination anti-HBs generation and does not influence a correlation between circulating IFN-λ3 levels and anti-HBs titers.

Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study.

BACKGROUND: There is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-associated gene (ENHO), retinoid X receptor α gene (RXRA), and liver X receptor α gene (LXRA). METHODS: The study included 1208 HD subjects. For diagnosis of dyslipidemia, both K/DOQI criteria and atherogenic index ≥3.8 were used. CASR rs1801725 was genotyped by TaqMan SNP Genotyping Assay, other SNPs - by high-resolution melting curve analysis or polymerase chain reaction-restriction fragment length polymorphism, as appropriate. Relative transcript levels of CASR, ENHO, RXRA, and LXRA were measured in peripheral blood mononuclear cells. The occurrence of dyslipidemic phenotypes concerning tested polymorphisms was compared using models of inheritance. Haplotypes were estimated using the Haploview 4.2 software. Epistatic interactions between tested SNPs were analyzed using the logistic regression and epistasis option in the PLINK software. RESULTS: Rs7652589 indicated a greater probability of atherogenic dyslipidemia in the dominant inheritance model (OR 1.4, 95%CI 1.0-2.0, P = 0.026), principally because of increased triglyceride (TG) levels. The rs1801725 variant allele was associated with a decreased probability of dyslipidemia characterized by non-HDL-cholesterol ≥130 mg/dL and TG ≥200 mg/dL (OR 0.6, 0.4-0.9, P = 0.012). There were no epistatic interactions between CASR and RXRA, LXRA, and ENHO regarding dyslipidemia. Both rs7652589 and rs1801725 SNPs were not in linkage disequilibrium (D' = 0.091, r2 = 0.003 for the entire HD group) and their haplotypes did not correlate with dyslipidemia. Relative CASR transcript was lower at a borderline significance level in patients harboring the rs1801725 variant allele compared with homozygotes of the major allele (0.20, 0.06-7.80 vs. 0.43, 0.04-5.06, P = 0.058). CASR transcript correlated positively with RXRA transcript (adjusted P = 0.001), LXRA transcript (adjusted P = 0.0009), ENHO transcript (borderline significance, adjusted P = 0.055), dry body weight (adjusted P = 0.035), and renal replacement therapy duration (adjusted P = 0.013). CONCLUSIONS: CASR polymorphisms (rs7652589, rs1801725) are associated with dyslipidemia in HD patients. CASR correlates with RXRA, LXRA, and ENHO at the transcript level. Further investigations may elucidate whether other CASR SNPs contribute to associations shown in this study.

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients.

BACKGROUND: The energy homeostasis-associated gene (ENHO), retinoid X receptor alpha gene (RXRA), and liver X receptor alpha gene (LXRA) are involved in adipogenic/lipogenic regulation. We investigated whether single-nucleotide polymorphisms in these genes (ENHO rs2281997, rs72735260; RXRA rs749759, rs10776909, rs10881578; LXRA rs2279238, rs7120118, rs11039155) are associated with dyslipidaemia, related comorbidities and survival of haemodialysis (HD) patients also tested for T-helper (Th) cell interleukin genes (IL). METHODS: The study was carried out in 873 HD patients. Dyslipidaemia was diagnosed by the recommendations of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (2003); atherogenic dyslipidaemia was referred to if the TG/HDL cholesterol ratio was equal to or higher than 3.8. Genotyping of ENHO SNPs, LXRA SNPs, and IL12A rs568408 was carried out using HRM analysis. RXRA SNPs, IL12B rs3212227, and IL18 rs360719 were genotyped using PCR-RFLP analysis. The circulating adropin concentration was determined in 126 patients by enzyme-linked immunosorbent assay. Survival probability was analysed using the Kaplan-Meier method in 440 patients followed through 7.5 years. RESULTS: Dyslipidaemia by K/DOQI was diagnosed in 459 patients (91% revealed hyper-LDL- cholesterolaemia), atherogenic dyslipidaemia was diagnosed in 454 patients, and 231 patients were free of dyslipidaemia by both criteria. The variant allele (T) of ENHO rs2281997 was associated with the hyper-LDL cholesterolaemic pattern of dyslipidaemia by K/DOQI. The frequency of atherogenic dyslipidaemia was lower in T-allele bearers than in CC-genotype patients. The rs2281997 T allele was associated with lower cardiovascular mortality in HD patients showing atherogenic dyslipidaemia. ENHO, RXRA, and LXRA showed epistatic interactions in dyslipidaemia. Circulating adropin was lower in atherogenic dyslipidaemia than in non-atherogenic conditions. RXRA rs10776909 was associated with myocardial infarction. Bearers of LXRA rs2279238, rs7120118 or rs11039155 minor alleles showed higher mortality. ENHO SNP positions fell within the same DNase 1 hypersensitivity site expressed in the Th1 cell line. Epistatic interactions occurred between rs2281997 and Th1 IL SNPs (rs360719, rs568408). CONCLUSIONS: Atherogenic dyslipidaemia occurs in HD patients in whom ENHO encodes less adropin. ENHO, RXRA, and LXRA SNPs, separately or jointly, are associated with dyslipidaemia, myocardial infarction, and survival in HD patients. Differences in the availability of transcription binding sites may contribute to these associations.

Self-Reported Physical Activity, Quality of Life, and Psychological Status in Relation to Plasma 25-Hydroxyvitamin D Concentration in Patients Treated with Hemodialysis.

BACKGROUND/AIMS: Vitamin D status is announced among factors that may influence physical performance and mental health. Our aim was to evaluate self-reported physical activity, quality of life, psychiatric functioning, and affects with respect to plasma 25-hydroxyvitamin D [25(OH)D] concentrations in HD patients. METHODS: The study was carried out in HD patients not receiving vitamin D supplements (n = 112). IPAQ-L, QLI-D, GHQ-28, and PANAS were used in psychological evaluations. Plasma 25(OH)D concentration was determined by a chemiluminescent microparticle immunoassay. RESULTS: Plasma 25(OH)D level was suboptimal in all patients (14.6 ± 4.1 ng/ml). Adjusted correlates of 25(OH)D concentration included the GG genotype of GC rs7041 (ß±SE: 1.77± 0.70, P=0.014), female sex (ß±SE: -2.19±0.75, P=0.004), and treatment with high flux HD (ß±SE: 2.59±0.69, P=0.0003). In adjusted analyses, circulating 25(OH)D showed the independent association with total activity related to domestic and gardening domain (ß±SE: 53.2±23.8, P=0.028), and with moderate-intensity activities (ß±SE: 54.9±27.4, P=0.048), but not with any of quality of life, psychiatric functioning, or affects measures. CONCLUSIONS: Vitamin D status is independently positively associated with physical activity in HD patients. Quality of life and mental health do not seem to be associated with circulating 25(OH)D under condition of its suboptimal levels.

[A positive test QuantiFERON-TB Gold In-Tube in a patient treated with continuous ambulatory peritoneal dialysis]. / Dodatni wynik testu QuniERON-TB Gold In-Tube u chorej leczonej ciagla ambulatoryjna dializa otrzewnowa.

Patients undergoing renal replacement therapy have a higher risk of developing tuberculosis (TBC) in comparison with normal renal function population. The anergy to the tuberculin skin test, the lack of characteristic clinical symptoms of TBC and typical radiographic signs, and high prevalence of extrapulmonary TBC make the diagnosis in dialysis patients difficult and often delay the treatment. In contrast to the active TBC, latent TBC infection (LTBI) is asymptomatic and is not a direct epidemiological problem. However, in patients with end-stage renal disease prepared for renal transplantation, it is an obstacle to qualifying for immunosuppressive therapy. Treatment of LTBI patients with antimycobacterial medication decreases about 90% risk of developing active TB. Therefore, the possibility of a fast and easy identification of LTBI in this group of patients is extremely important. Test QuantiFERON-TB Gold In-Tube (QFT-G) is a new, simple and rapid diagnostic tool in LTBI and active tuberculosis infection (in conjunction with previously used clinical and microbiological methods). This test has been approved and is used in many European countries and in the USA. In a 65-year old patient, treated for 5 years with continuous ambulatory peritoneal dialysis, positive QFT-G results were shownin the course of diagnosis before reporting to the transplant program. After conducting an extensive diagnosis for tuberculosis infection (epidemiological interview, clinical examination, imaging studies, cultures by MB/BacT and the conventional method, consultations with a pulmonologist), latent form of tuberculosis was diagnosed with unspecified location. Due to the positive QFT-G and the need for future immunosuppressive treatment after kidney transplantation, a three-month prophylactic treatment with Rifamazyd 450 mg per day was included. After treatment, the patient entered the waiting list for a kidney transplant. Test QFT-G, in conjunction with other conventional methods is a good and rapid diagnostic tool in the identification of LTBI.

Association of Circulating Endothelial Nitric Oxide Synthase Levels with Phosphataemia in Patients on Haemodialysis.

The amount of evidence indicates that hyperphosphataemia (HP) can induce endothelial damage and significantly impair endothelial nitric oxide synthase (eNOS) expression. There are no clinical studies that have assessed HP and its correlation with circulating eNOS concentration in patients with end-stage renal disease (ESRD). Our preliminary study aimed to evaluate the relationship between plasma inorganic phosphorus (P) levels and circulating plasma eNOS concentration in patients on haemodialysis (HD). A total of 50 patients on HD were enrolled to the study. They were divided into groups according to the tertiles of P. The examined HD group was also analysed and compared with controls as a whole group; then, the group was divided into patients with and without dyslipidaemia (D) as well as into those with and without type 2 diabetes mellitus (type 2 DM). A total of 26 age-matched healthy volunteers were included in the study as the control group. The plasma levels of eNOS in HD patients are reduced in comparison to those in healthy subjects. There was no difference in plasma eNOS concentrations between HD patients with type 2 DM and those without DM as well as between those with D and without D. In the entire group of HD patients, there were positive correlations between circulating levels of eNOS and plasma P concentrations. In HD patients with D, higher systolic and diastolic blood pressure were accompanied by decreased plasma eNOS concentrations. In conclusion, HP and high blood pressure appear to decrease the circulating eNOS levels. These findings demonstrate an additional negative impact of HP on eNOS activity.

SERPINA3: Stimulator or Inhibitor of Pathological Changes.

SERPINA3, also called α-1-antichymotrypsin (AACT, ACT), is one of the inhibitors of serine proteases, one of which is cathepsin G. As an acute-phase protein secreted into the plasma by liver cells, it plays an important role in the anti-inflammatory response and antiviral response. Elevated levels of SERPINA3 have been observed in heart failure and neurological diseases such as Alzheimer's disease or Creutzfeldt-Jakob disease. Many studies have shown increased expression levels of the SERPINA3 gene in various types of cancer, such as glioblastoma, colorectal cancer, endometrial cancer, breast cancer, or melanoma. In this case, the SERPINA3 protein is associated with an antiapoptotic function implemented by adjusting the PI3K/AKT or MAPK/ERK 1/2 signal pathways. However, the functions of the SERPINA3 protein are still only partially understood, mainly in the context of cancerogenesis, so it seems necessary to summarize the available information and describe its mechanism of action. In particular, we sought to amass the existing body of research focusing on the description of the underlying mechanisms of various diseases not related to cancer. Our goal was to present an overview of the correct function of SERPINA3 as part of the defense system, which unfortunately easily becomes the "Fifth Column" and begins to support processes of destruction.

Diagnostic Problems in C3 Glomerulopathy.

BACKGROUND: C3 glomerulopathies (C3GN) are a group of rare kidney diseases associated with impaired complement regulation. The effects of this disease include the accumulation of complement C3 in the kidneys. Based on the clinical data, as well as light, fluorescence, and electron microscopy results, the diagnoses were verified. The study group consisted of biopsy specimens, which were obtained from 332 patients who were diagnosed with C3 glomerulopathy. In all cases, histopathological examinations were performed; deposits of complement C3 and C1q components, as well as the immunoglobulins IgA, IgG, and IgM, were identified using immunofluorescence. Furthermore, electron microscopy was also performed. RESULTS: The histopathological examination results presented cases of C3GN (n = 111) and dense deposit disease (DDD; n = 17). The non-classified (NC) group was the most numerous (n = 204). The lack of classification was due to the poor severity of the lesions, even on the electron microscopic examination or in the presence of intense sclerotic lesions. CONCLUSIONS: In cases of suspected C3 glomerulopathies, we believe an electron microscopy examination is necessary. This examination is beneficial in mild-to-extremely-severe cases of this glomerulopathy, where the lesions are barely discernible when using immunofluorescence microscopy.

[Calcimimetic drugs in stage 3-5 chronic kidney disease]. / Leki kalcymimetyczne w stadium 3-5 przewleklej choroby nerek.

This review is focused on results of application of calcimimetic drug--cinacalcet in the treatment of secondary hyperparathyroidism in patients in 3-5 stage chronic kidney disease (CKD), excluding dialysis patients (stage 5D CKD). Oral administration of cinacalcet (15-180 mg/day) significantly reduced plasma parathormone (PTH) concentrations (> or = 30% as compared to the baseline values), but simultaneously side effects occurred, among them hypocalcemia and hyperphosphatemia. Hypocalcemia was a reason for cinacalcet withdrawal in 2-15% of patients. There is a lack of studies showing the influence of advantages and disadvantages of long-term administration of cinacalcet on outcome of 3-5 stage CKD patients.

The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia-A Narrative Review.

Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.

Seroconversion rate to positivity for antibodies against core antigen of hepatitis B virus and duration of renal replacement therapy.

BACKGROUND: Prevalence of total antibodies against core antigen (anti-HBc) of hepatitis B virus (HBV) is greater in longer dialysed patients, but there are no data indicating a relationship between the higher seroconversion rate to anti-HBc positivity and longer renal replacement therapy (RRT) vintage prior to seroconversion. Our aim was to evaluate the association between RRT duration and seroconversion to anti-HBc positivity. METHODS: An incidence of anti-HBc was evaluated in 425 anti-HBc-negative intermittent haemodialysis (IHD) patients: Group I included patients who underwent first anti-HBc testing 31 days from first IHD session, and Group II or III included patients with RRT duration < 3 or ≥ 3 years, respectively. Anti-HBc testing was repeated every 6-12 months. Sex, age, RRT duration, anti-HCV, HCV RNA, ALT, ASP, GGT, full vaccination series against HBV with developed anti-HBs titre > 10 IU/L, hepatitis history and underlying kidney diseases were used as independent variables predicting seroconversion to anti-HBc positivity. RESULTS: Seroconversion rate to anti-HBc positivity was 2.59, 2.12 and 2.44 episodes/100 patient-years in Group I (n = 174), II (n = 170) and III (n = 80), respectively. In the entire group, there were 15 seroconversions to anti-HBc and one seroconversion to HBsAg positivity. The only variable predicting seroconversion in all HBsAg-negative patients (n = 424) was the lack of full vaccination series against HBV with developed anti-HBs titre > 10 IU/L maintained during the study (ß - 0.112, P = 0.04). CONCLUSIONS: Seroconversion rate to anti-HBc positivity is not related to duration of RRT treatment but to ineffective vaccination against HBV.

Circulating vascular endothelial growth factor receptor 2 levels and their association with lipid abnormalities in patients on hemodialysis.

The aim of the present study was to examine the association between the levels of circulating vascular endothelial growth factor receptor (VEGFR)2 levels, serum lipid composition and plasma receptor for advanced glycation end-products (RAGE) expression in patients undergoing hemodialysis (HD). A total of 50 patients on HD (27 men and 23 women; median age, 66 years; age range 28-88 years; HD mean time, 29.0, 3.9-157.0 months) were enrolled. Age-matched healthy subjects (n=26) were used as the control group. Plasma VEGFR2 and RAGE levels were determined using ELISA. Dyslipidemia (D) in patients on HD was diagnosed according to the Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease. Circulating VEGFR2, RAGE and serum lipids were compared between dyslipidemic and non-dyslipidemic patients on HD and controls. In patients on HD, the plasma VEGFR2 levels were lower compared with those in the healthy population. D was associated with high plasma VEGFR2 levels. The triglyceride/HDL-cholesterol ratio was strongly associated with plasma VEGFR2 levels. The plasma VEGFR2 concentration was associated with circulating RAGE levels. Therefore, circulating VEGFR2 levels may be partly associated with lipid abnormalities and plasma RAGE levels in patients receiving HD.

Paraoxonase 1 concerning dyslipidaemia, cardiovascular diseases, and mortality in haemodialysis patients.

Paraoxonase 1 (PON1) is known for preventing atherosclerosis through lipid-modifying features, antioxidant activity, anti-inflammatory, anti-apoptosis, anti-thrombosis, and anti-adhesion properties. Uremic patients requiring haemodialysis (HD) are especially prone to atherosclerosis and its complications. We analysed the PON1 gene (PON1) polymorphisms and serum PON1 (paraoxonase) activity concerning dyslipidaemia and related cardiovascular diseases and mortality to show how they associate under uremic conditions modified by maintenance HD treatment. The rs662 AA + AG (OR 1.76, 95%CI 1.10-2.80, P = 0.018), rs854560 TT (OR 1.48, 95%CI 1.04-2.11, P = 0.031), and rs854560 AT + TT (OR 1.28, 95%CI 1.01-1.63, P = 0.040) contributed to the prevalence of atherogenic dyslipidaemia diagnosed by the triglyceride (TG)/HDL-cholesterol ratio ≥ 3.8. The normalized serum PON1 activity positively correlated with atherogenic dyslipidaemia (ẞ 0.67 ± 0.25, P = 0.008). The PON1 rs854560 allele T was involved in the higher prevalence of ischemic cerebral stroke (OR 1.38, 1.02-1.85, P = 0.034). The PON1 rs705379 TT genotype contributed to cardiovascular (HR 1.27, 95% CI 1.03-1.57, P = 0.025) and cardiac (HR 1.34, 95% CI 1.05-1.71, P = 0.018) mortality. All P-values were obtained in multiple regression analyses, including clinical variables. Multifaceted associations of PON1 with dyslipidaemia, ischemic cerebral stroke, and cardiovascular mortality in HD patients provide arguments for the consideration of PON1 and its protein product as therapeutic targets in the prevention of atherosclerosis and its complications in uremic patients.

Antibodies to core antigen of hepatitis B virus in patients on renal replacement therapy: association with demographic, clinical and laboratory data.

BACKGROUND: Total antibodies to core antigen of hepatitis B virus (anti-HBc) are a marker for previous or current infection with hepatitis B virus (HBV). Our aim was to examine the prevalence and incidence of anti-HBc in relation to demographic, clinical and laboratory data of patients treated with intermittent hemodialysis (IHD). METHODS: Predictors for anti-HBc positivity were evaluated in prevalence IHD patients with negative testing for surface antigen of HBV (HBsAg, n = 1,105) using the stepwise backward regression analysis. Patients starting IHD (n = 336) were introduced into the one-year prospective study evaluating seroconversion for anti-HBc. RESULTS: Anti-HBc positivity (19.5% of all patients) was predicted by lack of vaccination against HBV with developed protective titer of antibodies to HBsAg (beta = 0.592, p = 0.000), vintage of renal replacement therapy (RRT, beta = 0.206, p = 0.000), history of hepatitis (beta = 0.101, p = 0.000), and activity of alanine aminotransferase (beta = 0.057, p = 0.037). In 85 prospective patients who finished first IHD year, seroconversion rate for anti-HBc was 1.23 episodes/100 patient-years. CONCLUSIONS: Lack of or not effective vaccination against HBV is the strongest predictor for prevalence of anti-HBc positivity in RRT patients. Periodical determination of anti-HBc, usually not required, may be helpful in evaluation of current epidemiological status and risk for further HBV infection in dialysis centers.

[Infections with hepatitis B virus in hemodialysis units of Wielkopolska]. / Zakazenia wirusem zapalenia watroby typu B w wielkopolskich stacjach hemodializ.

OBJECTIVE: Epidemiological analysis of HBV infections in dialysis units of Wielkopolska. METHODS: Studies were carried out in 19 dialysis units, in which patients were treated with intermittent hemodialysis (IHD). Data were collected from 18.04.2007 to 18.06.2007. MAIN OBSERVATIONS: There were 39 persons with HBsAg(+) among 1140 patients (3.42%). Positive results of HBcAb were shown in 114 from 349 examined patients with HBsAg(-) (32.7%). The group with HBsAg(+) consisted of 7 women (17.9%) and 32 men (82.1%). Documented duration of HBV infection was 9.7 +/- 6.0 years. Eight patients before detection of HBsAg(+) were vaccinated against hepatitis B; 21 patients (53.8%) underwent surgical interventions or invasive diagnostic procedures. Transfusions of blood or blood-related products were documented in 17 cases (43.6%). HBV infection in at least 32 patients (82.1%) was not connected with IHD treatment (p = 0.000). Four patients (10.3%) showed symptoms of acute hepatitis. Eleven patients (28.2%) with HBsAg(+) had renal transplantation. Patients with HBsAg(-) were vaccinated against hepatitis B. Vaccination was not effective (level of HBsAb < 10 IU/l) in 244 patients (22.2%). CONCLUSIONS: HBV infection in patients with chronic kidney disease is most frequently detected before or due to initiation of IHD treatment. Over 20% IHD patients remains susceptible for HBV infection despite vaccination against hepatitis B.

Interferon­λ4 gene polymorphisms, circulating interferon λ3, and clinical variables in hemodialysis patients exposed to hepatitis E virus.

Introduction Factors associated with hepatitis E virus (HEV) infection are rarely recognized in patients on renal replacement therapy (RRT), and the results of studies are inconsistent. Objectives We aimed to search for determinants of HEV seroprevalence among polymorphisms of the interferon­λ4 gene (IFNL4) associated with seroclearance of hepatotropic viruses (IFNL4 rs12979860, rs8099917 near IFNL4), circulating interferon λ3 (IFN­λ3), and clinical variables of patients treated with hemodialysis (HD) in a HEV­endemic region. Patients and methods The study was carried out in 90 HD patients. HEV open reading frame 2 antigen (HEV Ag), immunoglobulin M and G antibodies to HEV (anti­HEV IgM and anti­HEV IgG, respectively) and IFN­λ3 were tested, and IFNL4 polymorphic variants (rs8099917, rs12979860) were genotyped. Survival analysis was conducted concerning anti­HEV IgG positivity. Results In the study group, there were 37.8% anti­HEV IgG­positive subjects. None was HEV Ag or anti­HEV IgM positive. HD modalities utilizing high­flux dialyzers (adjusted odds ratio [OR], 3.586; 95% confidence interval [CI], 1.142-11.263; P = 0.03) as well as major homozygosity in rs8099917 (adjusted OR, 4.933; 95% CI, 1.516-16.054; P = 0.008) and rs12979860 (adjusted OR, 3.537; 95% CI, 1.136-11.014, P = 0.03), but not circulating IFN­λ3 levels, were positive determinants of anti­HEV IgG positivity. Liver enzyme activities and C­reactive protein levels tested as response variables to HEV exposure, as well as survival probability, were not different between patients stratified by anti­HEV IgG positivity. Conclusions Among HD patients, IFNL4 polymorphisms and treatment with high­flux HD are explanatory variables for isolated anti­HEV IgG positivity indicating spontaneous HEV resolution.

Nodular pulmonary amyloidosis and Sjögren's syndrome in a patient treated with intermittent hemodialysis.

In the available literature, we have found the descriptions of 5 cases of nodular pulmonary amyloidosis associated with Sjögren's syndrome. In our practice, such a case has occurred in a patient with chronic renal failure. A 53-year-old woman underwent nephrological, rheumatological, and pulmonological examinations because of end-stage renal disease with a small cirrhotic kidney in renal ultrasound examination, pulmonary nodules, and xerophthalmia. Serological data revealed a slightly positive rheumatoid factor, antinuclear antibodies, anti-SS-A, anti-SS-B, and anti-RNP/Sm antibodies. Schirmer's test was positive on both sides and Sjögren's syndrome was recognized. Pulmonological examinations (the chest radiograph and CT scan, bronchofiberoscopy, culture of bronchial washings, bronchial biopsy, pleural effusion analysis, and a thick-needle biopsy) failed to determine the etiology of nodular changes in lungs. Immunofluorescence studies in the skin biopsy specimen showed IgM-positive staining. After 2 years of treatment with IHD, a toracoscopy was performed with enucleation of the nodules from the right lung. Histological examination showed massive deposits of amyloid, which allowed for a diagnosis of diffusive nodular pulmonary amyloidosis.

Salusins and adropin: New peptides potentially involved in lipid metabolism and atherosclerosis.

Dyslipidemia is one of the most potent risk factors for the development of atherosclerosis. The high atherosclerotic risk in dyslipidemic patients is associated with endothelial dysfunction. During the last two decades, novel bioactive peptides have emerged as potential biomarkers of endothelial dysfunction and dyslipidemia-salusins and adropin. Salusin-alpha is likely to prevent atherosclerosis, while salusin-beta may act as a potential proatherogenic factor. Adropin was recently identified as important for energy homeostasis and lipid metabolism. Adropin is closely related to the inhibition of atherosclerosis by up-regulation of the endothelial nitric oxide synthase expression through the vascular endothelial growth factor receptor-2. These peptides represent a novel target to limit diseases characterized by endothelial dysfunction and may form the basis for the development of new therapeutic agents for treating metabolic disorders associated with atherosclerosis.

Involvement of adropin and adropin-associated genes in metabolic abnormalities of hemodialysis patients.

AIMS: We examined the involvement of plasma adropin and adropin-associated genes (ENHO and RXRA) in metabolic abnormalities of hemodialysis (HD) patients. MAIN METHODS: Among 50 HD patients (27 males and 23 females, aged 65.2±12.6years, HD vintage 29.0, 3.9-157.0months), there were 26 dyslipidemics and 25 type 2 diabetics. Age-matched healthy subjects (n=26) served as controls. Adropin levels were determined using ELISA. Insulin resistance/sensitivity was assessed using the Homeostasis Model Assessment for Insulin Resistance and Quantitative Insulin Sensitivity Check Index. ENHO (rs2281997, rs72735260) and RXRA (rs10881578, rs10776909) were genotyped by HRM, RXRA rs749759 by PCR-RFLP. Circulating adropin, serum lipids, and insulin indices were compared between bearers of the minor allele of tested polymorphisms and major homozygotes (the dominant model of inheritance). KEY FINDINGS: HD patients showed lower circulating adropin concentration compared with controls. In dyslipidemic patients, plasma adropin was lower than that in non-dyslipidemics, but it was not significantly different in diabetics vs. non-diabetics or in patients with or without metabolic syndrome. Major homozygotes of ENHO rs2281997 seemed to have higher circulating adropin, whereas major homozygotes of RXRA (rs749759, rs10776909) showed lower levels. Major homozygotes of ENHO rs2281997 showed borderline lower insulin resistance compared with bearers of the minor allele. SIGNIFICANCE: In HD patients, lower plasma adropin concentration is associated with dyslipidemia. Major homozygosity of RXRA seems to have an opposite effect on plasma adropin compared with that of ENHO rs2281997.

Serum cardiac troponin T and effective blood flow in stable extracorporeal dialysis patients.

PURPOSE: We examined the association between extracorporeal dialysis (ED)-related effective blood flow (eQB) and serum cardiac troponin T (cTnT) as a possible indicator of silent myocardial damage in stable ED patients. METHODS: In a cross-sectional study, cTnT was determined in 247 ED patients dialyzed using stable eQB and dialysate flow (QD). In a prospective study, 91 patients were switched from low-flux (LF) to high-flux (HF) hemodialysis (HD), and subsequently, the eQB increased, and the QD decreased; 65 patients continued LF-HD with stable eQB and QD. Clinical/laboratory evaluations were performed at 0, 15, 36, and 53 weeks from the start of the study. RESULTS: In the cross-sectional study, the main cTnT predictors were dialysis vintage, age, eQB, phosphorus, and C-reactive protein. Patients with cTnT levels in the highest quartile were excluded from the analysis, and subjects dialyzed with eQB ≤316 ml/min exhibited lower cTnT levels compared with patients dialyzed with higher eQB (P = 0.002). The all-cause and cardiac mortality rates of 154 patients, without changes in ED modality for up to 42 months, were associated with the initial cTnT concentrations but not with the initial eQB. In the prospective study, higher values for eQB and cTnT were observed during HF-HD at weeks 36 (P = 0.045) and 53 (P = 0.01) of the present study. The initial cTnT, ∆eQB, and ∆albumin influenced the ∆cTnT. The all-cause and cardiac mortality rates were not different between LF and HF groups at 21 months after the prospective study was completed. CONCLUSION: In stable ED patients, higher eQB rates and QB/QD values might contribute to silent myocardial injury, particularly in patients with lower cTnT levels, but do not affect the outcome of ED patients.