Background: The population of elderly patients undergoing chronic hemodialysis is increasing, and anemia represents a frequent complication. The aim of our study was to evaluate the association between ultrafiltration rate (UFR) in hemodialysis and erythropoietin (EPO) response in elderly patients with end-stage kidney disease (ESKD). Methods: This was a multicenter, retrospective observational study, involving elderly patients (aged 65 years or more) under chronic hemodialysis therapy. Individuals were divided into two groups according to the UFR adjusted to weight (UFR/W): lower (UFR-N) or higher (UFR-H) than 10 mL/h/kg. EPO resistance index (ERI) was calculated. We evaluated the hemogram, reticulocyte count, and quantified markers of iron metabolism and inflammation. Results: A total of 193 patients were enrolled in the study: 141 patients met criteria for inclusion in UFR-N group and 52 in UFR-H group. Compared to UFR-N, patients in the UFR-H group presented significantly higher doses of erythropoiesis-stimulating agents (ESA) and ERI values, with similar hemoglobin (Hb) and inflammatory markers levels. In a sub-analysis, within patients presenting transferrin saturation (TSAT) lower than 20%, a more marked difference in ERI between UFR groups was observed, being much higher in UFR-H compared with UFR-N. In this subgroup (UFR-H with lower TSAT), levels of hepcidin were lower than in the other subgroups. Conclusions: Our data show that UFR appears to be a contributing factor of ESA response in elderly patients under hemodialysis, particularly in those with lower iron availability. These findings suggest that inadequate weight control and/or UF prescription seem to aggravate ESA needs to achieve target Hb.

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.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: −0.407, 0.272, −0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Abstract Background and Aims In chronic kidney disease (CKD), hypertension (HT) is commonly found during its development and is a leading cause for its progression. HT, dyslipidemia and visceral obesity are among the components of metabolic syndrome (MetS) and seem to associate with progression of CKD to end-stage kidney disease (ESKD). Enhanced levels of soluble tumor necrosis factor receptor 2 (sTNFR2) are known to associate with progressive CKD; and this biomarker was reported as an independent predictor of all-cause mortality in ESKD patients under dialysis. Concerning the TNFRSF1B gene, the polymorphism rs1061624 (A > G), located in the 3′-untranslated region (3′-UTR), was associated with the development of HT in men and with increased risk of MetS. The aim of this study was to determine the genotype frequencies of TNFRSF1B rs1061624 in ESKD patients with and without HT, and to evaluate its relationship with the circulating levels of some MetS biomarkers. Method We studied 277 ESKD patients on dialysis (recruited between 2016-2019), 170 diagnosed with HT and 107 without HT (no-HT group); age, sex, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and statin therapy were recorded. Real time PCR TaqMan SNP genotyping assay was used to assess genotype frequencies of TNFRSF1B rs1061624. We also evaluated the conventional lipid profile and the levels of oxidized low-density lipoprotein, adiponectin and leptin. Results The genotype frequencies in patients with and without HT were different (P = 0.002); the AA genotype was less frequent in HT than in no-HT group, while GG and AG genotypes were more frequent. Considering the AA genotype carriers, HT ESKD patients (n = 23), compared to the no-HT group (n = 33), presented lower adiponectin levels (P = 0.025); for the AG genotype carriers, HT group (n = 89) presented a trend towards lower adiponectin concentrations (P = 0.055), and were younger than no-HT patients (n = 48; P<0.001); in both comparisons, groups were matched for sex, BMI and number of patients under statins treatment, and in the first case also for age. Considering GG genotype, HT patients (n = 58) only differed from no-HT subjects (n = 26) in SBP, that was higher (P<0.001). Among HT patients, AG genotype carriers presented higher DBP (P = 0.004), lower values of leptin (P = 0.012) and leptin/adiponectin ratio (P = 0.022) and were younger (P<0.001) than GG genotype patients; compared to AA carriers, cholesterol levels were lower (P = 0.012). For the no-HT group, AG genotype patients presented lower DBP (P = 0.008) than AA genotype carriers. Conclusion The genotype frequencies were different in ESKD patients with and without HT, being G allele more frequent in HT. The HT ESKD patients with the AA or the AG genotypes seem to present lower adiponectin levels than the ESKD no-HT patients with the same genotypes. Acknowledgements This work was financed by CESPU, through the project SNPsCKD-GI2-CESPU-2022; FCT, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.

Abstract Background and Aims Enhanced levels of soluble tumor necrosis factor receptor 2 (sTNFR2) are known to associate with progressive chronic kidney disease (CKD), and is pointed as a potential biomarker for early detection of CKD; moreover, it has been reported as an independent predictor of all-cause mortality in end-stage renal disease (ESRD) patients under dialysis. Despite the increase in TNFR2 and in other inflammatory markers, recognized as risk factors for mortality in dialysis patients, the hypothesis that genetic polymorphisms of those biomarkers might modulate the inflammatory response and, thereby, the patients’ survival predisposition, has been poorly studied. Concerning TNFR2 genetic variants, a single nucleotide polymorphism in TNFR2 (+ 676 T/G; rs1061622), that results in amino acid change at position 196 (Met/Arg), was associated with higher levels of sTNFR2 in inflammatory conditions. The aim of this study was to determine the allelic frequencies of TNFR2 in ESRD patients and controls, and to evaluate its relationship with the circulating levels of inflammatory biomarkers. Method We studied 277 ESRD patients on dialysis and 32 controls, matched for gender, body mass index, and, as far as possible, for age. Real time PCR TaqMan SNP genotyping assay was used to assess allelic frequencies of TNFR2 (rs1061622). We also evaluated the circulating levels of TNF-alpha, sTNFR2, ferritin, hepcidin, elastase and cell-free DNA (cfDNA). Deaths occurring along 1-year follow-up period were recorded and mortality rates were assessed. Results ESRD patients presented higher levels of all studied biomarkers, as compared to controls; their overall mortality rate was 10.5%. Allelic frequencies in ESRD patients and controls were similar for TNFR2 (rs1061622) considering the homozygous and heterozygous individuals (χ2, p = 0.518). Concerning sTNFR2 values, no significant differences were observed between patients with genotypes TT, GG or TG. The GG genotype patients, compared to TT genotype carriers, presented significantly lower ferritin (p = 0.048), hepcidin (p = 0.038), elastase (p = 0.006) and cfDNA levels (p = 0.016); and compared to TG genotype patients, showed significantly lower ferritin (p = 0.039) and a trend towards lower values of hepcidin (p = 0.097), elastase (p = 0.079) and cfDNA (p = 0.0164). TG genotype patients showed higher TNF-alpha (p = 0.049) and a trend towards lower elastase (p = 0.081) than TT genotype subjects. The GG genotype patients presented a trend towards lower mortality rate (6.3%, 7.5%, and 12.4% for GG, TG and TT, respectively). Conclusion No differences were found in the allelic frequencies between controls and ESRD patients. The GG genotype patients for TNFR2 rs1061622 polymorphism showed decreased levels of inflammation, suggesting a more favorable inflammatory response, which is usually associated to a lower mortality risk in these patients. In accordance with the scientific community, recommending studies on genetic survival predisposition in dialysis patients, the polymorphisms of TNFR2 and of other inflammatory biomarkers deserve further studies. Acknowledgements: This work was financed by CESPU, through the project SNPsCKD-GI2-CESPU-2022; FCT, through the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.

For individuals with end-stage renal disease (ESRD), the novel coronavirus can present several additional challenges in disease self-management. This study aimed to explore the impacts of the COVID-19 pandemic in non-COVID-19 patients with ESRD undergoing in-center hemodialysis (HD). A mixed-methods study was conducted with a purposive sample recruited from one dialysis unit in Portugal. Quantitative data were collected retrospectively from patients' medical records from February 2020 (T1-before the outbreak) and from April 2020 (T2-during lockdown). Semi-structured interviews were conducted with 20 patients (66.9 +/- 11.9 years old) undergoing HD for an average of 46.1 months (+/- 39.5) in April 2020. Overall results suggested that dialysis adequacy and serum albumin levels decreased significantly at T2, while phosphorus levels increased. The findings from thematic analysis suggested several psychosocial negative impacts and impacts on disease and treatment-related health behaviors (eg, difficulties managing dietary restrictions during the lockdown and diminished physical activity), which can partially explain these quantitative results. However, some patients were also able to find positive impacts in this experience and problem-focused and emotional strategies were identified to cope with the demands of COVID-19. Several recommendations have been made to mitigate patients' emotional, relational, and educational unmet needs during the current pandemic and in the event of new outbreaks.

Abstract Background and Aims Chronic inflammation plays an important role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). The single nucleotide polymorphism (SNP) in the promoter region (-174G/C) of interleukin-6 (IL6) gene regulates the levels of this cytokine, which have been associated with a poor outcome in several pathologies. Our aims were to determine, according to the genotype distribution of this polymorphism, the association between the inflammatory mediators, high sensitivity C-reactive protein (hsCRP), IL6, and pentraxin 3 (PTX3), shown to be increased in ESRD, and to estimate the risk for all-cause mortality over a period of one year. Method 289 ESRD patients on hemodialysis (high-flux hemodialysis and hemodiafiltration) were included in this study. Real-Time PCR TaqMan SNP genotyping assays were used to assess allelic frequencies of IL6 (rs1800795). We evaluated the circulating levels of PTX3, hsCRP and IL6 using commercially available kits. Deaths occurring along 1-year follow-up period were recorded, and the all-cause mortality hazard ratio (HR), according to IL6 polymorphisms in this patient cohort were determined by Cox regression analysis. A p < 0.05 value was considered statistically significant. Results In all IL6 (-174G>C) genotypes, hsCRP was positively and significantly correlated with IL6. For hsCRP and PTX3, a positive correlation with significance was only found for the GG genotype. All genotypes showed positive correlations between IL6 and PTX3 circulating levels, although only the GG genotype achieved a significant value. The Cox regression survival analysis for all-cause mortality in ESRD patients, using as reference the heterozygous patients for IL6 polymorphism, showed that CC patients presented a significant higher mortality risk, with a HR of 3.275 [1.165 to 9.204]. Moreover, the median survival time of CC patients (100 [54 - 138] days) was lower than that presented by the GG genotype patients (211 [83 - 290] days, p < 0.05 vs. CC) and by the heterozygous patients (291 [72 - 332] days, p = 0.157 vs. CC). Conclusion We observed different correlation profiles between inflammatory biomarkers within each IL6 (-174G>C) genotype. The association of the CC genotype of the IL6 polymorphism with a poorer outcome and shorter survival time for ESRD patients was also observed. However, further studies are required and must consider the underlying individual genetic background, since the inflammatory state appears to be influenced by IL6 polymorphisms, which, in turn, might be determinant for disease progression and outcome. Acknowledgments This work was supported by Applied Molecular Biosciences Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

AbstractIntroductionCaring for a patient with end‐stage renal disease undergoing in‐centre haemodialysis can be a stressful experience, likely to involve significant burden. Within the context of the new coronavirus pandemic, these patients are highly vulnerable to infection by COVID‐19, which might increase the care demands and burden of family caregivers.AimThis study aimed to explore the subjective experiences of family caregivers of non‐COVID‐19 patients with end‐stage renal disease undergoing in‐centre haemodialysis during the COVID‐19 lockdown.Study designA qualitative study was performed with a purposive sample.MethodsSemi‐structured telephone interviews were conducted with 19 family caregivers (50.7 ± 14 years old) of patients undergoing in‐centre haemodialysis in April 2020.FindingsFour major themes were identified: (1) emotional distress; (2) changes in caregiving responsibilities; (3) educational and supportive needs; and (4) coping strategies to deal with the outbreak and with the lockdown.DiscussionThe findings suggest that family caregivers of patients undergoing in‐centre haemodialysis have to manage several additional care responsibilities due to COVID‐19 lockdown. The dialysis team should consider the development of educational and supportive interventions to meet family caregivers’ needs, mitigate emotional distress, fears and concerns, and prevent caregiver burden during the COVID‐19 pandemic.

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.

Cardiovascular disease (CVD) is the major cause of mortality and morbidity in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD) patients. Left ventricular hypertrophy (LVH) is a common cardiovascular complication in CKD. Growth differentiation factor (GDF)-15 increases in tissue injury and inflammatory states associated with cardiometabolic risk. GDF-15 and N-terminal pro B-type natriuretic peptide (NT-proBNP) are both synthesized by cardiomyocytes and may be associated with cardiorenal dysfunction. Our aim was to study the association of GDF-15 with LVH in ESRD patients on dialysis. This study included 196 ESRD patients on dialysis (hemodiafiltration and high-flux hemodialysis). Left ventricular mass (LVM) was evaluated through echocardiographic studies, corrected for body surface area and the values are presented as LVM index (LVMI). LVH was defined by a value of LVMI > 115 g/m2 in men and > 95 g/m2 in women. Patients were divided into two groups - LVH (n=131) and non-LVH (n=65). LVMI, clinical and analytical variables (age, body mass index, dialysis vintage, dialysis adequacy, GDF-15, NT-proBNP and pentraxin (PTX) 3 were evaluated. ESRD patients with LVH presented significantly higher levels of NT-proBNP and GDF-15, and a trend towards higher PTX3 values. In LVH patients, GDF-15 correlated positively and significantly with NT-proBNP and PTX3; LVMI correlated positively and significantly with pro-BNP and PTX3 levels; pro-BNP correlated significantly and positively with PTX3. Our data show that in ESRD patients on dialysis with LVH, GDF-15 is raised and shows a strong association with NT-proBNP, PTX3 and LVMI. Further studies are needed to clarify if the rise in GDF-15 is a cause or a consequence of LVH development. This work was supported by Applied Molecular Biosciences Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

Background. DNA damage and inflammation are common in end-stage renal disease (ESRD). Our aim was to evaluate the levels of circulating cell-free DNA (cfDNA) and the relationship with inflammation, anaemia, oxidative stress and haemostatic disturbances in ESRD patients on dialysis. By performing a 1-year follow-up study, we also aimed to evaluate the predictive value of cfDNA for the outcome of ESRD patients. Methods. A total of 289 ESRD patients on dialysis were enrolled in the study: we evaluated cfDNA, haemogram, serum iron, hepcidin, inflammatory and oxidative stress markers, and haemostasis. Events and causes of deaths were recorded throughout the follow-up period. Results. ESRD patients, as compared with controls, presented significantly higher levels of cfDNA, hepcidin, and inflammatory and oxidative stress markers, and significantly lower values of iron and anaemia-related haemogram parameters. The all-cause mortality rate was 9.7%; compared with alive patients, deceased patients (n = 28) were older and presented significantly higher values of inflammatory markers and of cfDNA, which was almost 2-fold higher. Furthermore, cfDNA was the best predictor of all-cause mortality and cardiovascular mortality in ESRD patients, in both unadjusted and adjusted models for basic confounding factors in dialysis. Conclusions. Our data show cfDNA to be a valuable predictive marker of prognosis in ESRD patients on dialysis treatment; high levels of cfDNA were associated with a poor outcome.

Abstract Background and Aims Dyslipidemia is common in chronic kidney disease (CKD) and cardiovascular disease (CVD)-related events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. Concerning lipid management, clinical practice emphasized treatment escalation to achieve specific low-density lipoprotein cholesterol (LDLc) targets, which implies repeated LDLc evaluations, and enhancement of statin doses or combination of lipid-lowering therapies. However, the LDLc target is not consensual, with some entities suggesting 100 mg/dl and others a more conservative level. It has been hypothesized that lipoprotein’s quality (size, composition and functionality) may be more important than their total circulating levels, as CVD risk factor. Our aim was to evaluate and compare, in ESRD patients on dialysis and under statins treatment, the levels of lipoprotein fractions and subfractions and inflammatory markers, between patients who achieved LDLc levels < 100 mg/dl and those who did not achieve that target. Method We studied 110 ESRD patients on dialysis (high-flux hemodialysis or hemodiafiltration) and under statin therapy; 87 presented a LDLc < 100 mg/dl (group 1) and 23 a value > 100 mg/dl (group 2); levels of high-sensitivity C-reactive protein (hsCRP), interleukin(IL)-6, lipid profile including lipoprotein fractions/subfractions, and oxidized LDL (oxLDL) were evaluated. Results Group 1, as compared to group 2, presented lower values of total cholesterol (TC), triglycerides, oxLDL, TC/high-density lipoprotein cholesterol (HDLc) and LDLc/HDLc ratios. Concerning lipoprotein fractions/subfractions, group 1 presented significantly higher larger and intermediate LDL, and a trend towards lower small LDL (P=0.063), higher large HDL (P=0.069) and lower small HDL (P=0.080); no significant alterations were found for very-low-density lipoprotein and intermediate-density lipoprotein. Regarding inflammatory markers, no significant differences were observed between the 2 groups. Conclusion Patients who achieved the LDLc < 100 mg/dl target presented a better non-conventional lipid profile, including lower oxLDL levels and an increase in larger (less atherogenic) LDL subfractions. According to our data, a lower LDLc level associates with a better lipid profile; the benefits of this improvement on HDL fractions and CVD-related events in ESRD patients on dialysis needs to be better clarified.

Abstract Background and Aims Chronic inflammation plays an important role in progression and outcome of chronic kidney disease (CKD) patients. The interleukin-6 (IL-6) polymorphism, rs1800795, is a single nucleotide polymorphism (SNP) in the promoter region (-174G/C) that regulates gene transcription and affects the levels of this cytokine. Genetic variants in the promotor region have been associated with a poor outcome in several pathologies, namely in coronary artery disease. Pentraxin 3 (PTX3) is an inflammatory protein, produced locally by different cell types (e.g. mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells). PTX3 polymorphism, rs2305619, is a SNP (+281A>G) in the intron 1 of PTX3 gene. PTX3 polymorphisms have been described as risk factor for development of coronary artery disease and for an impairment of kidney function. Our aim was to determine the allelic frequencies of IL6 and PTX3 in end-stage renal disease (ESRD) patients and controls, as well as their relationship with the inflammatory response. Method We studied 289 ESRD patients on hemodialysis (high-flux hemodialysis or hemodiafiltration) and 22 healthy individuals, matched for gender, body mass index, and, as far as possible, for age. Real-Time PCR TaqMan SNP genotyping assays were used to assess allelic frequencies of IL6 (rs1800795) and PTX3 (rs2305619). We evaluated the circulating levels of PTX3, growth differentiation factor (GDF)-15, high-sensitivity C-reactive protein (hsCRP), IL-6, tumor necrosis factor-alpha (TNF-α), soluble TNF receptor 2 (sTNFR2), hepcidin and transferrin, using commercially available kits. Deaths occurring along 1-year follow-up period were recorded and mortality rates were evaluated for homozygous and heterozygous alleles. Results Compared to controls, all inflammatory biomarkers were significantly higher in ESRD patients. Allelic frequencies in ESRD patients and controls were similar for both SNPs, IL-6 -174G/C and PTX3 +281A>G, considering the homozygous and the heterozygous alleles. For the IL-6 -174G/C, the CC patients, compared to GG and heterozygous patients, showed significantly higher GDF-15 and CRP concentrations and significantly lower values of transferrin; moreover, we found that CC patients presented a trend towards higher mortality rate (21%, 10% and 7% for CC, GG and GC, respectively; P=0.072). For PTX3 +281A>G polymorphism, the AA patients, compared to GG and heterozygous patients, presented higher hsCRP; no significant differences were found in mortality rate between different allele carrier groups (P=0.703). Conclusion Although no differences were found in the allelic frequencies between controls and ERSD patients, the CC patients for IL6 polymorphism (rs1800795) and AA patients for PTX3 polymorphism (rs2305619), showed an enhanced inflammatory response; the association of the IL6 polymorphism with a higher mortality needs further studies.

Abstract Background and Aims In patients with end-stage renal disease (ESRD) on hemodialysis, the preservation of residual kidney function may result in a diversity of benefits in terms of survival and quality of life. The control of fluid and electrolyte homeostasis may play an important role in this setting. Elevated predialysis serum potassium is a common electrolyte disturbance that may worsen patient’s outcomes. Our aim was to study the impact of furosemide therapy in predialysis serum potassium levels, indicators of estimated residual renal function, and inflammatory markers, in ESRD patients under hemodialysis; moreover, we aimed to study the impact of furosemide-associated changes on mortality rate. Method A cross-sectional study was carried out on 289 adult patients on chronic dialysis therapy (hemodiafiltration and high flux hemodialysis). Patients were divided in 2 groups: the diuretic group (DG, n=116; 120.0 (IQR: 80-160) mg/daily median furosemide dose) and the non-diuretic group (NDG, n = 173), in which patients did not use furosemide. A large set of data was analyzed, encompassing hematological data, serum electrolyte parameters, inflammatory markers, dialysis adequacy, and biomarkers of residual kidney function. A 2-year follow up study was also performed by registering events of death (all-cause mortality). Results The DG patients, compared with NDG patients, presented: significantly lower predialysis serum potassium; more favorable blood biomarkers of kidney function - lower β-trace protein, cystatin C, creatinine and urea; greater residual glomerular filtration rate derived from equations with cystatin C, creatinine and creatinine–cystatin C; lower inflammation (significantly lower levels of high-sensitivity C-reactive protein); intradialytic ultrafiltration volume (L) was similar for the two groups. Mortality was significantly lower for DG patients, compared with NDG (13.6% versus 24.7%; P=0.029). Conclusion In ESRD patients under chronic dialysis, we found a significant association between current diuretic therapy and lower predialysis serum potassium levels, more favorable biomarkers of kidney function and a decreased inflammatory response that seem to contribute to a higher survival rate. Acknowledgments: The work was supported by UIDB/04378/2020 with funding from FCT/MCTES through national funds, by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

Abstract Background and Aims Cardiovascular (CV) disease events are the major cause of death in end-stage renal disease (ESRD) patients on dialysis. Left ventricular hypertrophy, myocardial stress and disturbances in nutritional status are common findings in ESRD patients on dialysis. The adipokines, adiponectin and leptin, are known as important mediators of cardiometabolic risk in obesity, although their role in ESRD patients is poorly clarified. N-terminal pro B-type natriuretic peptide (NT-proBNP) is synthesized within cardiac myocytes, in response to cardiac wall stress. Our aim was to study the association of left ventricular hypertrophy with adipokines (adiponectin and leptin), myocardial stress (ProBNP) and nutritional status (BMI and albumin) in ESRD patients on dialysis. Method This study included 196 ESRD patients on dialysis (hemodiafiltration and high-flux hemodialysis). LVH was defined by a value of LVMI > 115 g/m2 in men and 95 g/m2 in women. Patients were divided into two groups - LVH (n=131) and non-LVH (n=65). Left ventricular mass (LVM) was evaluated through echocardiographic studies, corrected for body surface area and the values are presented as LVM index (LVMI). LVMI, clinical and analytical variables (age, body mass index, dialysis vintage, dialysis adequacy, albumin, adiponectin, leptin, NT-proBNP and hemoglobin concentration) were evaluated. Results The prevalence of LVH was 66.8%; LVH patients presented significantly higher levels for NT-proBNP, and significantly lower levels for hemoglobin, when compared with non-LVH patients; a trend towards (P=0.052) lower leptin values were observed. No differences were observed between groups, for age, BMI, dialysis vintage, URR, Kt/V, eKt/V, ultrafiltration volume, albumin and adiponectin. In LVH patients, we found that LVMI presented significant positive correlations with NT-proBNP and with adiponectin; and, significant negative correlations with markers of dialysis adequacy (URR and eKt/V) and leptin. Conclusion Our data suggest that a higher LVMI in ESRD patients is associated with higher myocardial stress, with lower leptin and higher adiponectin levels, showing no association of these adipokines with increased cardiovascular risk and with worsening of left ventricular hypertrophy. Further studies are needed to understand the roles of these adipokines, considering the controversial association with left ventricular hypertrophy, a cardiovascular risk condition. Acknowledgments: The work was supported by UIDB/04378/2020 with funding from FCT/MCTES through national funds, by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).