Publications by authors named "Maria do Sameiro Faria"

32 Publications

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center.

J Bras Nefrol 2021 May 12. Epub 2021 May 12.

Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Porto, Portugal.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years.

Methods: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed.

Results: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months).

Conclusion: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.
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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0199DOI Listing
May 2021

Identifiable relatives in the family history: not without individual consent.

Porto Biomed J 2020 Mar-Apr;5(2):e62. Epub 2020 Mar 26.

Escola de Direito da Universidade do Minho, Braga, Portugal.

The family history is a traditional section of the clinical record. Data on family members in the clinical record may be anonymous but yet these may be easily identifiable; therefore, exposing the relatives of the patient to the fact that a written record is produced, mentioning them, without their consent. This is in direct contradiction with European data protection and other regulations and in contradiction with a reasonable ethical perspective. For the purpose of obtaining an image of the present state of affairs, we used as a convenience sample, the series of Case Records published in 2019 in (January to December). From a total number of 40 reports, identifiable relatives were present in 30. The number of identifiable relatives varied between none and 6. It is not the right of each individual to disclose sensitive clinical information regarding other persons, without consent from these latter. Family history should no longer include identifiable relatives, unless consent is obtained from each identifiable person. The authors offer the following guidelines on this topic: (1) Do not mention any identifiable relative of the patient in the medical history without consent from the said relative; (2) Do not mention in the family history clinical conditions seemingly unrelated to the present clinical situation; (3) Do not mention in the family history clinical conditions that the patient does not (him/) herself have and that may be seen as social stigmata; (4) Consult the institutional Ethics committee in case of reasonable doubt.
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http://dx.doi.org/10.1097/j.pbj.0000000000000061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722405PMC
March 2020

Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality.

Mediators Inflamm 2019 16;2019:3295725. Epub 2019 Jun 16.

UCIBIO, REQUIMTE, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.
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http://dx.doi.org/10.1155/2019/3295725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604294PMC
February 2020

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

Ren Fail 2019 Nov;41(1):662-672

a UCIBIO, REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy , University of Porto , Porto , Portugal.

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. 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. 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. 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.
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http://dx.doi.org/10.1080/0886022X.2019.1635893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691825PMC
November 2019

Infants with congenital nephrotic syndrome have comparable outcomes to infants with other renal diseases.

Pediatr Nephrol 2019 04 29;34(4):649-655. Epub 2018 Oct 29.

Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.

Background: Children with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of dialysis in these children.

Methods: We conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS.

Results: Eighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4-14) months. Of these, 17 (39%) were on dialysis by the age of 6 months, 30 (68%) by 1 year, and 40 (91%) by 2 years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (n = 5) or peritonitis (n = 4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6 months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6-18) months, and the median age at transplantation was 22 (14-28) months.

Conclusions: Infants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data.
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http://dx.doi.org/10.1007/s00467-018-4122-0DOI Listing
April 2019

Management of children with congenital nephrotic syndrome: challenging treatment paradigms.

Nephrol Dial Transplant 2019 08;34(8):1369-1377

Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Background: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective.

Methods: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS.

Results: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died.

Conclusion: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
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http://dx.doi.org/10.1093/ndt/gfy165DOI Listing
August 2019

Potential cardiovascular risk protection of bilirubin in end-stage renal disease patients under hemodialysis.

Biomed Res Int 2014 10;2014:175286. Epub 2014 Sep 10.

Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal ; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.

We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients.
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http://dx.doi.org/10.1155/2014/175286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174976PMC
June 2015

Risk factors for mortality in hemodialysis patients: two-year follow-up study.

Dis Markers 2013 24;35(6):791-8. Epub 2013 Nov 24.

Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade Farmácia, Universidade do Porto, Porto, Portugal ; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal ; Serviço de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.

Background: End-stage renal disease (ESRD) patients under hemodialysis (HD) have high mortality rate. Inflammation, dyslipidemia, disturbances in erythropoiesis, iron metabolism, endothelial function, and nutritional status have been reported in these patients. Our aim was to identify any significant association of death with these disturbances, by performing a two-year follow-up study.

Methods And Results: A large set of data was obtained from 189 HD patients (55.0% male; 66.4 ± 13.9 years old), including hematological data, lipid profile, iron metabolism, nutritional, inflammatory, and endothelial (dys)function markers, and dialysis adequacy.

Results: 35 patients (18.5%) died along the follow-up period. Our data showed that the type of vascular access, C-reactive protein (CRP), and triglycerides (TG) are significant predictors of death. The risk of death was higher in patients using central venous catheter (CVC) (Hazard ratio [HR] = 3.03, 95% CI = 1.49-6.13), with higher CRP levels (fourth quartile), compared with those with lower levels (first quartile) (HR = 17.3, 95% CI = 2.40-124.9). Patients with higher TG levels (fourth quartile) presented a lower risk of death, compared with those with the lower TG levels (first quartile) (HR = 0.18, 95% CI = 0.05-0.58).

Conclusions: The use of CVC, high CRP, and low TG values seem to be independent risk factors for mortality in HD patients.
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http://dx.doi.org/10.1155/2013/518945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857718PMC
July 2014

Partially reversible cardiomyopathy after renal transplant associated with anti-troponin I antibodies.

Cardiology 2013 31;126(3):173-4. Epub 2013 Aug 31.

Faculdade de Medicina, Universidade do Porto, Porto, Portugal.

Cardiomyopathy associated with dialysis has been shown to be reversible in some cases. A 58-year-old female patient with polycystic renal disease and end-stage renal disease had a renal transplant after 9 years on hemodialysis. Dilated cardiomyopathy with depressed left ventricular ejection fraction markedly improved after transplantation, with normalization of the ejection fraction. High titers for anti-troponin I antibodies were measured: IgG 1:640, IgM 1:80. In our case, the presence of anticardiac (anti-troponin I) antibodies may suggest that the syndrome of reversible cardiomyopathy seen after renal transplantation is associated with immunosuppression therapy acting on immunological mechanisms previously at play.
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http://dx.doi.org/10.1159/000353262DOI Listing
June 2014

Body mass index and resistance to recombinant human erythropoietin therapy in maintenance hemodialysis patients.

Ren Fail 2013 2;35(10):1392-8. Epub 2013 Sep 2.

Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto , Porto , Portugal .

The aim of this work was to contribute to a better understanding of the relationship between resistance to recombinant human erythropoietin (rhEPO) therapy and body mass index (BMI) in hemodialysis (HD) patients. We evaluated 191 HD patients and 25 healthy individuals. Complete blood count, reticulocyte count, and circulating levels of ferritin, transferrin, iron, soluble transferrin receptor (sTfR), transferrin saturation, hepcidin, C-reactive protein (CRP), interleukin 6 (IL-6), albumin, and adiponectin were measured in all patients and controls. Non-responder patients (n = 16), as compared with responder patients (n = 175), showed statistically significant lower BMI values, an enhanced inflammatory and higher adiponectin levels, associated with disturbances in iron metabolism. Analyzing the results according to BMI, we found that underweight patients required higher rhEPO doses than normal, overweight, and obese patients, and a higher percentage of non-responders patients were found within the underweight group of HD patients. Moreover, underweight patients presented lower levels of transferrin and higher levels of adiponectin compared to overweight and obese patients, and lower levels of iron compared with normal weight patients. Multiple regression analysis identified the sTfR, hemoglobin, BMI, and albumin as independent variables associated with rhEPO doses. In conclusion, our work showed that HD patients resistant to rhEPO therapy present a functional iron deficiency and a higher degree of inflammation, despite their lower BMI values and higher levels of adiponectin. Actually, BMI is poorly related with markers of systemic inflammation, such as IL-6 and CRP, while adiponectin works a fairly good indirect marker of adiposity within HD patients.
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http://dx.doi.org/10.3109/0886022X.2013.828267DOI Listing
June 2014

Circulating cell-free DNA levels in hemodialysis patients and its association with inflammation, iron metabolism, and rhEPO doses.

Hemodial Int 2013 Oct 16;17(4):664-7. Epub 2013 May 16.

Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1111/hdi.12055DOI Listing
October 2013

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

J Vasc Access 2013 Oct-Dec;14(4):335-41. Epub 2013 May 3.

FMC, Dinefro - Diálises e Nefrologia, SA - Portugal and Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto - Portugal.

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.
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http://dx.doi.org/10.5301/jva.5000132DOI Listing
August 2014

Main determinants of PON1 activity in hemodialysis patients.

Am J Nephrol 2012 22;36(4):317-23. Epub 2012 Sep 22.

Faculdade de Farmácia, Serviço de Bioquímica, Portugal.

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.
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http://dx.doi.org/10.1159/000342235DOI Listing
April 2013

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

Scand J Urol Nephrol 2012 Dec 2;46(6):461-5. Epub 2012 Aug 2.

FMC, Dinefro - Diálises e Nefrologia - SA , Portugal.

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.
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http://dx.doi.org/10.3109/00365599.2012.708943DOI Listing
December 2012

Oxidized low-density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene.

Hemodial Int 2012 Oct 20;16(4):481-90. Epub 2012 Apr 20.

Faculdade Farmácia, Serviço de Bioquímica, Universidade do Porto, Porto, Portugal.

Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).
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http://dx.doi.org/10.1111/j.1542-4758.2012.00687.xDOI Listing
October 2012

Neutrophil and monocyte activation in chronic kidney disease patients under hemodialysis and its relationship with resistance to recombinant human erythropoietin and to the hemodialysis procedure.

Hemodial Int 2010 Jul;14(3):295-301

Biochemistry Department, Faculty of Pharmacy, University of Porto, Porto, Portugal.

The aim of the present work was to further clarify leukocyte activation due to hemodialysis (HD) procedures and to investigate its relationship with recombinant human erythropoietin resistance. Therefore, we studied the expression of CXCR1 and CD11b on neutrophils, as well as the monocyte expression of CD11b, HLA-DR, and CD14. We studied 34 chronic kidney disease (CKD) patients under HD and recombinant human erythropoietin treatment (26 responders and 8 nonresponders to recombinant human erythropoietin therapy). All CKD patients' blood samples were collected before and immediately after the HD procedure. Eighteen healthy individuals (blood donors) were also studied as a control group. Hematological data, neutrophil (CD11b and CXCR1), and monocyte (CD11b, HLA-DR, and CD14) cell surface markers were measured in all patients (before and after the HD procedure) and controls. When compared with the controls, CKD patients presented a significant decrease in CXCR1 neutrophil expression, and in CD14 monocyte expression, accompanied by a significant increase in HLA-DR monocyte expression. When comparing the 2 groups of patients, we found that nonresponders showed an additional decrease in CXCR1 neutrophil expression. After the HD procedure, a statistically significant increase in CD14 and CD11b monocyte surface markers and a decrease in CXCR1 neutrophil expression and in HLA-DR monocyte expression was found. These data further strengthen our previous studies, showing that neutrophils and monocytes are activated in CKD patients, particularly in nonresponder patients. Moreover, this activation is due, at least in part, to the HD procedure, although we should not exclude that it can also be due to the enhanced inflammatory process observed in nonresponder patients.
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http://dx.doi.org/10.1111/j.1542-4758.2010.00450.xDOI Listing
July 2010

Changes in red blood cells membrane protein composition during hemodialysis procedure.

Ren Fail 2008 ;30(10):971-5

Faculdade de Farmácia, Serviço de Bioquímica, Universidade do Porto, Porto, Portugal. elisio_

Our aim was to evaluate the influence of the hemodialysis (HD) procedure in red blood cells (RBC) membrane protein composition. We evaluated hematological data (RBC count, hemoglobin concentration, and hematimetric indices) and RBC membrane protein composition (linear and exponential gradient polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate [SDS-PAGE] followed by densitometry analysis of RBC membrane proteins) before and immediately after the HD procedure in 20 patients (10 responders and 10 non-responders to recombinant human erythropoietin therapy [rhEPO]) and 26 healthy controls. Before HD, patients presented anaemia and significant changes in membrane protein composition, namely, a statistically significant reduction in spectrin associated with a significant increase in bands 6, as well as an altered membrane protein interaction (protein 4.1/spectrin, protein 4.1/band 3, protein 4.2/band 3 and spectrin/band 3). After HD, we found that patients showed a statistically significant increase in RBC count and hemoglobin, a further and statistically significant decrease in spectrin, an increase in band 3, and an altered spectrin/band 3 ratio. When comparing responders and non-responders patients after HD, we found that the non-responders presented a trend to a higher reduction in spectrin. Our data suggest that HD procedure seems to contribute to a reduction in spectrin, which is normally associated with a reduction in RBC deformability, being that reduction in spectrin is higher in non-responder patients.
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http://dx.doi.org/10.1080/08860220802422036DOI Listing
February 2009

Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients.

Am J Nephrol 2008 30;28(6):935-40. Epub 2008 Jun 30.

Faculdade Farmácia, Serviço de Bioquímica, Universidade do Porto, Porto Portugal.

Aim: The aim of this work was to evaluate the neutrophil activation state in chronic kidney disease (CKD) patients under hemodialysis, and its linkage with resistance to recombinant human erythropoietin (rhEPO) therapy.

Methods: We studied 63 CKD patients under hemodialysis and rhEPO treatment (32 responders and 31 non-responders to rhEPO therapy). In 20 of the CKD patients (10 responders and 10 non-responders to rhEPO therapy), blood samples were also collected immediately after dialysis. Twenty-six healthy volunteers were included in a control group. Hemoglobin levels, total and differential leukocyte counts, and circulating levels of C-reactive protein (CRP), elastase and lactoferrin were measured in all patients and controls.

Results: Compared with controls, CKD patients presented with significantly higher CRP, neutrophil and elastase levels. When we compared the 2 groups of patients, we found that non-responders presented statistically significantly higher elastase plasma levels. A positive significant correlation was found between elastase levels and weekly rhEPO dose and CRP serum levels. After the hemodialysis procedure, a statistically significant rise in elastase, lactoferrin and, elastase/neutrophil and lactoferrin/neutrophil ratios were found.

Conclusions: Our data show that CKD patients under hemodialysis present higher elastase levels (particularly in non-responding patients), which could be related to the rise in neutrophils, and to be part of the enhanced inflammatory process found in these patients.
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http://dx.doi.org/10.1159/000142147DOI Listing
December 2008

Altered erythrocyte membrane protein composition in chronic kidney disease stage 5 patients under haemodialysis and recombinant human erythropoietin therapy.

Blood Purif 2008 17;26(3):267-73. Epub 2008 Apr 17.

Serviço de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.

Our aim was to evaluate red blood cell (RBC) membrane protein composition in chronic kidney disease (CKD) stage 5 patients under haemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapy, and its linkage to rhEPO hyporesponsiveness. We evaluated in 63 CKD stage 5 patients (32 responders and 31 non-responders to rhEPO therapy) and in 26 healthy controls RBC count, haematocrit, haemoglobin concentration, haematimetric indices, reticulocyte count, reticulocyte production index, RBC osmotic fragility test and membrane protein analyses. CKD stage 5 patients presented significant changes in membrane protein composition, namely a reduction in spectrin, associated to altered protein 4.1/spectrin and spectrin/band 3 ratios. Non-responder CKD stage 5 patients were more anaemic, with more microcytic and anisocytic RBCs, than responders; significantly altered ankyrin/band 3 and spectrin/ankyrin ratios were also observed. CKD stage 5 patients under HD are associated with an altered protein membrane structure, which seems to the disease itself and/or to the interaction with HD membranes.
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http://dx.doi.org/10.1159/000126922DOI Listing
September 2008

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

Am J Nephrol 2008 20;28(4):677-83. Epub 2008 Mar 20.

Escola Superior de Saúde, Instituto Politécnico de Bragança, Bragança, Portugal.

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.
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http://dx.doi.org/10.1159/000121478DOI Listing
July 2008

Cardiac Fabry's disease: an unusual cause of left ventricular hypertrophy.

Nat Clin Pract Cardiovasc Med 2007 Nov;4(11):630-3

Faculdade de Medicina do Porto, Alameda Prof Hernâni Monteiro, 4200 Porto, Portugal.

Background: A 64-year-old male was observed as an outpatient with atypical, non-exercise-induced chest pain and palpitations. He had arterial hypertension and marked concentric left ventricular hypertrophy. After 2.5 years of antihypertensive drug therapy the patient's blood pressure had returned to normal, but his left ventricular hypertrophy was unchanged.

Investigations: Electrocardiography, transthoracic echocardiography, myocardial perfusion scintigraphic imaging, measurement of alpha-galactosidase A activity, gene sequencing, brain MRI, carotid artery ultrasonography, biochemical renal evaluation and cardiac Doppler tissue imaging.

Diagnosis: Cardiac Fabry's disease.

Management: Losartan, hydrochlorothiazide, low-dose aspirin and bisoprolol. The patient is expected to begin enzyme replacement therapy.
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http://dx.doi.org/10.1038/ncpcardio1012DOI Listing
November 2007

Glomerular filtration rate and coronary artery disease burden in patients with acute coronary syndrome.

Clin Cardiol 2007 Sep;30(9):464-8

Faculty of Medicine, University of Porto, Porto, Portugal.

Background: Mild renal dysfunction may be associated with increased cardiovascular morbidity and mortality.

Methods: The relation between estimated glomerular filtration rate (eGFR), as calculated from plasma creatinine at admission, and coronary artery disease burden (CADB), was studied in a cohort of 110 patients with acute coronary syndrome and coronary atherosclerosis.

Results: A relatively weak but significant negative correlation was found between eGFR and CADB as measured by angiography (coefficient correlation of - 0.26, probability value of 0.006); a similar association was seen in multiple regression analysis, taking CADB as dependent variable, and eGFR, age, plasma calcium and plasma phosphorus as independent variables. After dividing the 110 patients into eGFR tertiles (with mean values of 102.9 +/- 22.8, n = 37, 75.7 + or - 5.6, n = 36, and 53.1 +/- 13.4, n = 37, all in mL/min per 1.73 m(2)), mean CADB values of the lower and higher eGFR tertiles were found to be significantly different (270.6 +/- 176.4 and 192.9 +/- 78.5, respectively). Similar mean values for CADB and for eGFR were noted when patients with elevated ST segment/new left bundle branch block and patients with nonelevated ST segment acute coronary syndrome were compared.

Conclusions: We conclude that renal function of patients with acute coronary syndromes and coronary atherosclerosis, as estimated at admission, is negatively correlated with coronary artery disease burden. It is unknown whether renal dysfunction acts as a cause for accelerated coronary artery disease or if it merely acts as a surrogate marker for the overall systemic vascular system status.
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http://dx.doi.org/10.1002/clc.20145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652889PMC
September 2007

Renal diseases: a 27-year renal biopsy study.

J Nephrol 2006 Jul-Aug;19(4):500-7

Department of Nephrology, Hospital Sao Joao, Faculty of Medicine, University of Porto, Portugal.

Background: Data from registries of renal biopsy (RB), currently an important source for diagnosing renal disease, are available for a number of countries, but different patterns seem to exist in different countries.

Methods: We reviewed the records of all patients who underwent an RB at our institution over a 27-year period (January 1, 1977, to December 31, 2003), in northern Portugal, a European region with a predominantly Caucasian population. We aimed at identifying patterns of glomerular disease frequency, as well as the corresponding changes over time. The patients were grouped for analysis in 9-year intervals: period A (1977 through 1985), period B (1986 through 1994) and period C (1995 through 2003).

Results: Nephrotic syndrome was the most common clinical presentation for RB (42.0%), followed by urinary abnormalities (28.5%), acute renal failure (9.7%), chronic renal failure (9.3%) and nephritic syndrome (9.3%). Primary glomerulonephritis (GN) was the most common type of kidney disease in the present study, representing 50.4% of all renal pathology, followed by secondary GN (29.4%) and vascular and tubulointerstitial diseases (14.0%). The relative frequency of secondary GN and vascular and tubulointerstitial diseases increased significantly over time, and so did IgA nephropathy, the most common type of primary glomerular disease in the present study (31.2%). Focal and segmental glomerulosclerosis represented 6.9% of primary glomerular disease, and its frequency did not increase in the time period under study. Regarding secondary glomerular diseases, apparent changes were noted in the incidence of a number of diseases, including vasculitis, thin glomerular basement membrane disease and Henoch-Schönlein pur-pura. A somewhat similar situation was noted with vascular and tubulointerstitial diseases.

Conclusions: We conclude that, as occurs in other European and Asiatic populations, and unlike the findings in the American continent, IgA nephropathy is the most frequent glomerular disease in our population.
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November 2006

Apnea/hypopnea index and benzodiazepine use in patients with arterial hypertension and excessive weight.

Int J Cardiol 2007 Jan 2;114(3):416-8. Epub 2006 May 2.

Sleep apnea may be associated to psychological symptoms and to increase use of antidepressant drugs. It is unknown if the use of benzodiazepines, psychoactive drugs with a depressant effect on the brain, is similar, in this regard, to antidepressant drugs use. Thirty patients with treated arterial hypertension and excessive weight (body mass index >25), either regularly using (13 patients) or not using (17 patients) benzodiazepines, were studied, by comparing the apnea/hypopnea index measured in a sleep study in both groups. Cardiac left chamber dimensions, corrected QT interval, body weight, height and mass index, as well as cervical and abdominal circumferences, were additional parameters under study. The mean apnea/hypopnea index was found to be significantly greater in patients not under chronic benzodiazepine use, when compared to the other group of patients (21.8+/-12.4, n=17 versus 9.7+/-11.3, n=13, p<0.05). Mean cervical and abdominal diameters were also greater in patients not treated with benzodiazepines. We conclude that, in this small group of patients with treated arterial hypertension and excessive weight, chronic benzodiazepine therapy was not associated with a greater mean apnea/hypopnea index. Further studies are needed to establish if, in fact, an inverse association might exist.
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http://dx.doi.org/10.1016/j.ijcard.2005.11.111DOI Listing
January 2007