Impact of TNFRSF1B (rs3397, rs1061624 and rs1061622) and IL6 (rs1800796, rs1800797 and rs1554606) Gene Polymorphisms on Inflammatory Response in Patients with End-Stage Kidney Disease Undergoing Dialysis.

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD.

The 2021 Portuguese Society of Ophthalmology joint guidelines with Paediatric Rheumatology on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis.

AIM: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). METHODS: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. RESULTS: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). CONCLUSION: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available. KEY-WORDS: juvenile idiopathic arthritis, uveitis, biological treatment, conventional immunosuppressive treatment, multidisciplinary management, guidelines, consensus, review, Delphi Technique.

Evaluation of Functional Vision and Eye-Related Quality of Life in Children with Strabismus.

Background: Understanding how strabismus impacts a child's quality of life, as well as their families, should be an important key to guide treatment, not only from the ophthalmological point of view but also regarding psychological and social aspects, which are fundamental for a healthy and harmonious development. Methods: A cross-sectional study was performed to evaluate the functional vision and eye-related quality of life (ER-QOL) in a population of children with strabismus submitted or not to corrective surgery, using the recently developed Pediatric Eye Questionnaire (PedEyeQ) and to compare with age and gender-matched visually normal children. The PedEyeQ was applied to non-operated children with strabismus (n = 18), operated children with strabismus (n = 24), and visually normal children (n = 21). This instrument is composed of 3 components (Child, Proxy, and Parent) and has different versions according to the child's age (0-4, 5-11, or 12-17 years-old versions). Clinical data such as age, type of strabismus, angle of deviation, amblyopia, occlusion treatment, and surgical outcome were also recorded. Results: All PedEyeQ domain scores were significantly lower in children with strabismus compared with visually normal children, except the Child "functional vision" domain. Children with strabismus with successful corrective surgery had significantly lower scores in many domains of the Child, Proxy, and Parent components, compared with visually normal children. Conclusion: This study showed that strabismus has an important impact on affected children and their families, as assessed by PedEyeQ. Interestingly, children with prior successful corrective strabismus surgery had worse PedEyeQ scores compared to visually normal children. Educational programs and psychosocial rehabilitation interventions should be implemented in children with strabismus and their families.

Refractive Surgery for Older Children and Adults with Accommodative Esotropia: A Systematic Review.

INTRODUCTION: Accommodative esotropia (AET) is characterized by an esodeviation of the eyes due to uncorrected hyperopia, deficient fusional divergence, or high accommodative convergence. Decreasing hyperopia would reduce accommodative convergence and strabismus. We sought to review the existing evidence regarding the outcomes of refractive surgery in patients with AET. METHODS: A four-database search (Pubmed, ISI Web of Science, Cochrane, and Scopus) was performed from inception to March 2021 using the following MeSH terms: ("Refractive Surgical Procedures" OR "Keratomileusis, Laser In Situ" OR "Photorefractive Keratectomy" OR "Lens Implantation, Intraocular") AND ("Esotropia" OR "Accommodative Esotropia" OR "Refractive Esotropia" OR "Accommodative Strabismus"). No meta-analysis was performed due to studies' heterogeneity. RESULTS: Twenty-eight studies including 22 case series enrolling 378 patients and 6 case reports enrolling 8 patients were selected among 185 original abstracts. In the case series, a total of 378 patients (726 eyes) were recruited with an age range of 8-52 years. All studies reported mean follow-up periods of at least 12 months. Photorefractive keratectomy was performed in 7 studies, laser-assisted in situ keratomileusis in 9 studies, laser-assisted sub-epithelial keratectomy was reported in 1 study, and 3 studies implanted intraocular lenses, including iris-fixated and collamer. Considering the adult patients with a preoperative corrected esodeviation ≤10 prism diopters (PD) (n = 129), all but 5 (3.9%) presented orthophoria or ≤10PD after refractive surgery. All children but 4 (4.5%) ended up with an esodeviation ≤10PD after surgery with those exceptions being in the range of 11-15PD. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7-34 years and a follow-up range of 4-48 months. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7-34 years and a follow-up range of 4-48 months. CONCLUSION: Evidence produced so far points out that refractive surgery may be an alternative for spectacle correction for adults with AET ≤10PD. There is not enough evidence to recommend its use for patients under 18 years of age. The safety and predictability of these procedures for this purpose remains unclear as the selection criteria used for these patients are much different than the usual indications and there are no studies with long-term follow-up.

Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis.

Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The circulating levels of the inflammatory biomarkers interleukin 6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients, and are associated with the progression of the disease and with higher risk for cardiovascular events, the major cause of death in CKD patients. Our aim was to study how specific polymorphisms of IL6 and PTX3 encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. Methodology included the analysis of two single nucleotide polymorphisms (SNP), namely the IL6 (rs1800795) polymorphism in the promoter region (-174G > C), and the PTX3 (rs2305619) polymorphism in the intron 1 (+ 281A > G), which were analyzed in ESRD patients on dialysis and in a group of heathy individuals. The allelic frequencies, genotype distribution and their association with circulating levels of the inflammatory markers C-reactive protein (CRP), IL6, growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients. Events of death were recorded along one year, to assess the association of the studied SNPs with all-cause mortality and the inflammatory biomarkers, in ESRD patients. Results showed that the allelic frequencies and genotype distribution for IL6 and PTX3 SNPs in the control group and ESRD patients were similar and in agreement with other European reports. For the IL6 polymorphism, we found a trend towards higher levels of high-sensitivity (hs) CRP, IL6 and PTX3 in the homozygous genotypes; the CC genotype also showed the highest levels of GDF15. The mortality rate after the 1-year follow-up was 10.4%. The CC genotype (IL6 SNP) was associated to a higher risk of mortality and deceased patients carrying this genotype also showed the highest levels of hsCRP. Regarding the studied PTX3 SNP, the AA genotype was linked to an enhanced inflammatory response, showing the highest values of hsCRP and IL6. Nevertheless, this genotype had no significant impact on the mortality rate. In conclusion, both studied SNPs seem to modulate the inflammatory response in ESRD and may, therefore, be determinant on disease progression and patients' outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY PARAMETERS IN PATIENTS WITH PHACOMATOSIS.

PURPOSE: To compare the retinal vasculature characteristics between eyes of patients with and without phacomatosis. METHODS: Case-control observational study with retinal vasculature evaluation by optical coherence tomography and optical coherence tomography angiography of the macula and disk. RESULTS: The study included 80 eyes. Neurofibromatosis Type 1 patients presented with a higher central macular thickness (P = 0.007), a lower optical disk nervous fiber layer (P = 0.006), a lower perimeter, area, and circularity of the foveal avascular zone (P < 0.05), a higher vascular density of macular avascular layer (AMVD) (P = 0.004), and a lower papillary vascular density of superficial capillary plexus (SPVD) (P = 0.048). Patients with tuberous sclerosis presented with an increase in central macular thickness (P = 0.024) and in vascular densities (P < 0.05) [except for macular vascular density of deep capillary plexus (PMVD), AMVD, and SPVD]. Patients with Sturge-Weber syndrome showed a decrease in optical disk nervous fiber layer (P < 0.001), subfoveal choroid thickness (P = 0.011), macular vascular density of superficial capillary plexus (SMVD) (P = 0.036), and SPVD (P < 0.001). CONCLUSION: Phacomatosis patients showed statistically significant differences of retinal vasculature characteristics, compared to eyes without pathology. Further studies are needed to determine when and if these parameters change with the course of the disease and if they can be used as biomarkers for disease severity or progression.

Hepcidin and diabetes are independently related with soluble transferrin receptor levels in chronic dialysis patients.

Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

Aplicação do modelo WINROP no rastreio de Retinopatia de Prematuridade (ROP) numa amostra de prematuros portugueses / Application of the WINROP model in Retinopathy of Prematurity (ROP) screening in a Portuguese cohort of premature infants

Resumo Objetivo: Avaliar a sensibilidade e especificidade do algoritmo WINROP na deteção de retinopatia de prematuridade (ROP) numa amostra de prematuros portugueses. Métodos: Estudo retrospetivo que incluiu todos os recém-nascidos prematuros (RN) submetidos a rastreio de ROP no Centro Hospital Universitário do Porto entre Janeiro de 2010 a Maio de 2016. A idade gestacional (IG), peso à nascença e os pesos semanais dos RN, até uma idade pós-menstrual de 35-36 semanas, foram introduzidos na aplicação online do WINROP, que sinaliza com uma mensagem de alarme os RN em risco de desenvolver ROP tipo 1, que requer tratamento. Resultados: De um total de 496 RN submetidos a rastreio de ROP, 20 foram excluídos do estudo por registos incompletos e 101 por IG≥32 semanas. Dos RN com uma IG≥ 32 semanas, um desenvolveu ROP tipo 1 e foi submetido a tratamento. Dos 375 RN introduzidos no modelo WINROP, 231 (62%) registaram um sinal de alarme. Todos os RN com ROP tipo 1 foram identificados pelo sinal de alarme. O tempo médio entre o sinal de alarme e o tratamento foi de 11 semanas. O algoritmo WINROP apresentou uma sensibilidade e um valor preditivo negativo de 100% e uma especificidade de 42%. Conclusão: O modelo WINROP demonstrou ser sensível na deteção de prematuros com necessidade de tratamento. Embora com um valor de especificidade menor, a aplicação do algoritmo pode ajudar a reduzir substancialmente o número de exames realizados. Uma das limitações do modelo consiste na exclusão de RN com IG≥32 semanas.

Abstract Objective: To evaluate the sensitivity and specificity of the WINROP algorithm for predicting retinopathy of prematurity (ROP) in a population of Portuguese preterm infants. Methods: Retrospective study of all newborns who underwent ROP screening at Hospital Universitário do Porto from January 2010 to May 2016. Gestational age (GA), birthweight and weekly postnatal weight measurements of the newborns, up to a postmenstrual age of 35-36 weeks, were entered in the online application of WINROP, which signals with an alarm the newborns who are at risk of developing ROP type 1, which requires treatment. Results: Of a total of 496 RN undergoing ROP screening, 20 were excluded from the study by incomplete records and 101 by GA ≥32 weeks. Of the newborns with a GA≥32 weeks, one developed ROP type 1 and was treated. Of the 375 newborns introduced in the WINROP application, 231 recorded an alarm signal. All the newborns with type 1 ROP were identified by the alarm signal. The WINROP algorithm presented a sensitivity and a negative predictive value of 100% and a specificity of 41%. The mean time between the alarm signal and the treatment was 10 weeks plus 6 days. Conclusion: The WINROP model was 100% sensitive in the detection of preterm infants requiring treatment for ROP. Besides its lower specificity, WINROP application can reduce substantially the number of exams in ROP screening. One of the limitations of the model is the exclusion of newborns with GA≥32 weeks.

Anterior Chamber Flare as an Objective and Quantitative Noninvasive Method for Oculopathy in Transthyretin V30M Amyloidosis Patients.

PURPOSE: Assess the aqueous humor flare in transthyretin V30M amyloidosis patients (ATTRV30M). MATERIALS AND METHODS: This is a retrospective, cross-sectional, noninterventional comparative study including 28 ATTRV30M patients with a unilateral scalloped iris. For comparative analysis, the fellow eye, the nonscalloped iris eye, from each patient was used as control. All patients underwent aqueous humor flare meter and intraocular pressure (IOP) measurements. RESULTS: Mean aqueous humor flare was significantly higher in the eyes with the scalloped iris than the control group with the nonscalloped iris (14.1 ± 2.2 versus 6.5 ± 0.9 pc/ms, respectively). No significant differences in IOP were found in the scalloped iris eyes than those in the nonscalloped iris control group (17.1 ± 0.8 versus 16.8 ± 0.7 mmHg, respectively). No significant correlation was not found between the flare and the IOP value within groups. CONCLUSIONS: In this study, aqueous humor flare values in the scalloped iris eyes may be a valid marker for controlling the stage of the oculopathy in ATTRV30M patients.

Preverbal visual photo screening Project implementation in Portugal / Implementação de projeto de foto rastreio visual pré-verbal em Portugal

Abstract Purpose: To present the design and implementation of an amblyopia risk factors screening project, in a large based Portuguese population. Methods: Two referral centers have been enrolled to assess all children aged 2 under their direct referral area. The photoscreener used was PlusOptix ® A09. At this age, the cut-off defined for referral was: ≥1 Diopter (D) of anisometropia, ≥1.5D of astigmatism, ≥2D of myopia and ≥1.5D of hyperopia. The results were reported to a reading platform that allowed the ophthalmologist to see all exams, and provide timely appointment with a complete ophthalmologic assessment for those who needed. Results: A total of 2867 photo screens were made to the population eligible to both referral centers, which comprises a coverage rate of 55%. Out of 2611 children under one of the referral area, 53% (n=1395) adhered to the screening. Within these children, 17.5% (n=245) were referred and 15.3 % (n=214) appointments were performed. The comparison of refraction between PlusOptix ® and cycloplegic refraction showed a strong correlation regarding the sphere and cylinder values. From the 214 children observed in consultation, glasses were prescribed in 25.7% (n=55), corresponding to 3.9% of all screened children under one of the referral area. This screening method showed a positive predictive value of 58.4%. Conclusion: This screening program may be highly relevant to eradicate untreated amblyopia from our population. The results may lead to the implementation of this project to the whole country.

Resumo Objetivo: Apresentação da implementação de um projeto de rastreio de fatores de risco de ambliopia, numa população alargada portuguesa. Métodos: dois centros de referência foram selecionados para avaliar todas as crianças de 2 anos, na sua área de referenciação direta. Para o foto rastreio foi utilizado o PlusOptix ® A09. Nesta idade, os valores definidos para referenciação foram: ≥1 Dioptria (D) de anosimetropia, ≥1.5 D de astigmatismo, ≥2 D de miopia e ≥1.5 D de hipermetropia. Os resultados foram reportados a uma plataforma de leitura que permitiu ao oftalmologista ver todos os exames e providenciar uma consulta oportuna com uma avaliação oftalmológica completa para aqueles que precisavam. Resultados: Foram realizados 2867 foto rastreios na população elegível para ambos os centros de referência, perfazendo uma taxa de cobertura de 55%. Das 2611 crianças sob uma área de referência, 53% (n = 1395) aderiram ao rastreio. Dentro desse grupo, 17,5% (n = 245) foram referenciadas e 15,3% (n = 214) consultas foram realizadas. Verificou-se uma forte correlação entre a refração do PlusOptix® e a refração cicloplégica. Das 214 crianças observadas em consulta, foram prescritos óculos em 25,7% (n = 55), correspondendo a 3,9% de todas as crianças sob uma área de referência. Este método de triagem mostrou um valor preditivo positivo de 58,4%. Conclusão: Este programa de rastreio pode ser altamente relevante para erradicar a ambliopia não tratada na nossa população. Os resultados podem levar à implementação deste projeto em todo o país.

Vascular access versus the effect of statins on inflammation and fibrinolysis in renal dialysis patients.

PURPOSE: The aim of this work was to assess the effect of statin therapy on inflammatory and fibrinolytic/endothelial (dys)function markers in end-stage renal disease (ESRD) patients under hemodialysis (HD), according to the type of vascular access. METHODS: This transversal study includes 191 ESRD patients under regular HD, divided into four groups according to vascular access and statin therapy: 87 patients with arteriovenous fistula (AVF) and no statins (AVF-NS), 61 with AVF and statins (AVF-S), 27 with central venous dialysis catheter (CVC) and no statins (CVC-NS) and 16 with CVC and statins (CVC-S). The basic lipid profile and fibrinolytic/endothelial cell function markers were assessed. RESULTS: Patients with CVC presented significantly higher levels of D-dimers compared with AVF groups. CVC-NS patients also presented the highest IL-6 values, which were significantly higher than those presented by CVC-S patients. AVF-S patients presented significantly higher t-PA and PAI-1 values and lower adiponectin levels compared with AVF-NS. CONCLUSIONS: Our results demonstrate that patients with CVC, particularly those not under statin therapy, present a higher production and turnover of fibrin. We also found that statin therapy decreases inflammation in CVC patients but is associated with a reduction of adiponectin and increased endothelial function marker levels in AVF patients.

The use of intravitreal ranibizumab to treat neovascular glaucoma because of retinal amyloid angiopathy in familial amyloidosis transthyretin v30m related.

PURPOSE: The purpose of this study to report a patient with amyloidotic angiopathy and neovascular glaucoma who was treated with intravitreal injection of ranibizumab followed by laser photocoagulation. METHODS: A 52-year-old liver-transplanted woman with familial amyloidotic polyneuropathy presented with unilateral rubeosis iridis and neovascular glaucoma. A complete ocular examination and fluorescein and indocyanine green angiography were performed. RESULTS: Best-corrected visual acuity before injection was 0.05 (Snellen) in the left eye, and intraocular pressure was 42 mmHg. Fluorescein angiography showed vascular occlusion in the retinal periphery, focal staining of vessels, and microaneurysms. Indocyanine green angiography showed hyperfluorescent spots alongside the choroidal veins. Two days after receiving intravitreal injection of ranibizumab, the clinical picture regressed. The diagnosis of retinal amyloid angiopathy was made, and a peripheral retinal laser photocoagulation was done. The final best-corrected visual acuity after 2 years of follow-up was 0.4 (Snellen) in the left eye. CONCLUSION: Intravitreal injections of ranibizumab should be evaluated for a potential role on the treatment of amyloid angiopathy neovascular glaucoma. Careful retinal periphery examination should be included in the ophthalmologic examination of all familial amyloidotic polyneuropathy patients.

Main determinants of PON1 activity in hemodialysis patients.

BACKGROUND/AIMS: Cardiovascular diseases are the major cause of morbidity and mortality in hemodialysis (HD) patients. These patients present reduced paraoxonase 1 (PON1) activity that depends on genetic and non-genetic factors; however, how these factors influence PON1 activity in HD patients is poorly clarified. Our aim was to evaluate the influence of two polymorphisms and non-genetic factors on PON1 activity in HD patients. METHODS: We evaluated 183 HD patients under recombinant human erythropoietin (rhEPO) treatment and 22 healthy individuals. The lipid profile [total cholesterol, triglycerides, HDL-c, LDL-c, apolipoprotein (Apo) A-I, Apo B, lipoprotein(a) and oxidized low-density lipoprotein (Ox-LDL)], inflammatory markers [adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP)], PON1 activity and PON1 gene polymorphisms (L55M and Q192R) were evaluated. RESULTS: HD patients presented higher levels of IL-6, CRP and Ox-LDL/LDL-c, and lower PON1 activity, total cholesterol, HDL-c, LDL-c, Apo A and Apo B; the most frequent genotype was heterozygosity for L55M polymorphism and homozygosity for the Q allele, the more frequent genotype of Q192R polymorphism. Multiple regression analysis identified heterozygosity and homozygosity for L55M and Q192R polymorphisms, very low-density lipoproteins, LDL-c, Apo A and CRP levels, time on dialysis and rhEPO dose, as the independent variables significantly associated with PON1 activity. The associations with CRP, rhEPO and time on dialysis were negative. CONCLUSION: Our results show that the reduced PON1 activity in HD patients who are not under statin therapy is strongly associated with inflammation, longer time on dialysis and high rhEPO doses, suggesting that the reduction in PON1 activity may worsen the prognosis of these patients.

Adiponectin is an independent predictor of tissue plasminogen activator levels in patients under haemodialysis.

OBJECTIVE: The aim of this study was to evaluate the association of tissue-type plasminogen activator (t-PA) levels with clinical data of patients under haemodialysis (HD) and with several variables potentially related to endothelial function and dysfunction. MATERIAL AND METHODS: In a cross-sectional study involving 189 Portuguese HD patients, circulating levels of t-PA, lipids, oxidized low-density lipoprotein (Ox-LDL), interleukin-6 (IL-6), C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor type 1 (PAI-1) and fibrin fragment D-dimer were measured. RESULTS: Considering the entire population, t-PA correlated inversely and significantly with adiponectin and high-density lipoprotein-cholesterol, and positively and significantly with age, body mass index, PAI-1, IL-6, CRP, D-dimer, cholesterol and Ox-LDL. In multiple linear regression analysis PAI-1, age and adiponectin remained statistically associated with t-PA values (p < 0.01 for all). The weakest significant association (p = 0.046) was that found between t-PA and D-dimer. CONCLUSION: Adiponectin is a main determinant of t-PA level, which may be a good marker of endothelial dysfunction in HD patients.

Role of prohepcidin, inflammatory markers and iron status in resistance to rhEPO therapy in hemodialysis patients.

The aim of our study was to assess possible relations between prohepcidin, iron status and inflammatory markers in hemodialysis (HD) patients, as well as its association with resistance to recombinant human erythropoietin (rhEPO) therapy. Fifty HD patients and 25 healthy controls were enrolled in the study. Among HD patients, 25 were non-responders and 25 were responders to rhEPO therapy. Complete blood cell count, reticulocyte count, and circulating levels of ferritin, iron, transferrin saturation, C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), soluble transferrin receptor (s-TfR), IL-6 and prohepcidin were measured in all patients and controls. HD patients showed higher circulating levels of ferritin, s-TfR, CRP, IL-6, s-IL2R and prohepcidin, and lower levels of transferrin compared to healthy controls. Higher levels of s-TfR, CRP and lower levels prohepcidin were observed among non-responders compared to responders. Prohepcidin levels correlated negatively with s-TfR and reticulocyte count. The weekly rhEPO/kg dose was found to be positively correlated with CRP, hemoglobin and s-TfR. In conclusion, our data show that a close interaction exists between inflammation, iron status and prohepcidin serum levels that ultimately regulate intracellular iron availability. Prohepcidin and s-TfR, together with CRP, may prove to be good markers of resistance to rhEPO therapy in HD patients.