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- Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal DialysisPublication . Branco, Patrícia; Calça, Rita; Martins, Ana Rita; Mateus, Catarina; Jervis, Maria João; Gomes, Daniel Pinto; Azeredo-Lopes, Sofia; De Melo Junior, Antonio Ferreira; Sousa, Cátia; Civantos, Ester; Mas-Fontao, Sebastian; Gaspar, Augusta; Ramos, Sância; Morello, Judit; Nolasco, Fernando; Rodrigues, Anabela; Pereira, Sofia AzeredoPeritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.
- Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney DonorsPublication . Ribeiro, Luís Costa; Almeida, Manuela; J, Malheiro; Silva, Filipa; Nunes-Carneiro, Diogo; Martins, La Salete; Pedroso, Sofia; Silva-Ramos, MiguelBackground: Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. Methods: This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. Results: The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). Conclusions: Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.
- Living Donors’ Age Modifies the Impact of Pre-Donation Estimated Glomerular Filtration Rate on Graft SurvivalPublication . Almeida, Manuela; Ribeiro, Catarina; Silvano, José; Pedroso, Sofia; Tafulo, Sandra; Martins, La Salete; Ramos, Miguel; J, MalheiroBackground: The global scarcity of organs for kidney transplants (KTs) has led to the increased acceptance of living donors (LDs) with minor abnormalities to increase the donor pool.. We sought to evaluate the effects of some of these LDs' clinical characteristics (older age, borderline renal function, hypertension, dyslipidemia, smoking, and obesity) on graft outcomes. Methods: We studied 352 recipients of LDKTs (1998-2020). Firstly, considering the recipients and KT variables, we identified relevant predictors of overall and censored graft failure (GF). Then, adjusting for these predictors, we explored LD variables as predictors of overall and censored GF in a multivariable Cox model. Results: The recipients from LD with higher eGFR (≥90 mL/min/1.73 m2) had significantly better overall and censored graft survival GS) at 15 y after KT (respectively, 67 and 75% vs. 46 and 46%, p < 0.001). Importantly, none of the remaining LD factors which were evaluated (hypertension, dyslipidemia, smoking, proteinuria, and obesity) were independent predictors of GF. In recipients from LDs < 50 y, having an eGFR < 90 was an independent predictor of overall GF [adjusted HR (95%CI) of 2.578 (1.120-5.795)] and censored GF [adjusted HR (95%CI) of 3.216 (1.300-7.959)], compared to recipients from LDs with eGFR ≥ 90. Contrarily, when donors were older, no difference in the risk of GF was observed between eGFR categories. Conclusion: In our cohort, lower pre-donation eGFR had an impact on GS only in younger LDs. An age-adjusted eGFR cutoff may be pursued for improved donor admissibility.
- CT volumetry performs better than nuclear renography in predicting estimated renal function one year after living donationPublication . Almeida, Manuela; Pereira, Pedro R.; Ramos, Miguel; Nunes-Carneiro, Diogo; Mandaleno, Mariana; Silva, Filipa; Pedroso, Sofia; França, Manuela; Martins, La Salete; J, MalheiroThe evaluation of split renal function (SRF) is a critical issue in living kidney donations and can be evaluated using nuclear renography (NR) or computerized tomography (CT), with unclear comparative advantages. We conducted this retrospective study in 193 donors to examine the correlation of SRF assessed by NR and CT volumetry and compared their ability to predict remaining donor renal function at 1 year, through multiple approaches. A weak correlation between imaging techniques for evaluating the percentage of the remaining kidney volume was found in the global cohort, with an R2 = 0.15. However, the Bland-Altman plot showed an acceptable agreement (95% of the difference between techniques falling within - 8.51 to 6.11%). The predicted and observed eGFR one year after donation were calculated using the CKD-EPI, and CG/BSA equations. CT volume showed a better correlation than NR for both formulas (adjusted R2 of 0.42. and 0.61 vs 0.37 and 0.61 for CKD-EPI and CG/ BSA equations, respectively). In non-nested modeling tests, CT volumetry was significantly superior to NR for both equations. CT volumetry performed better than NR in predicting the estimated renal function of living donors at 1-year, independently from the eGFR equation.
- Greater Impact of Living Donation Than HLA Mismatching in Short-Term Renal Allograft SurvivalPublication . Ribeiro, Bárbara; Reis Pereira, Pedro; Oliveira, João; Almeida, Manuela; Martins, La Salete; J, MalheiroIntroduction: Living donor kidney transplantation (LDKT) is accepted as first-line treatment for patients with end-stage kidney disease with advantages over deceased donor kidney transplantation (DDKT). Still, how the known detrimental effect of HLA mismatch (MM) may hamper these advantages remains unsettled. We sought to determine the effect of the degree of HLA MM, separately in deceased and living donor renal allograft outcomes. Methods: We evaluated all adults submitted to LDKT and DDKT at our center between 2006 and 2018. Their HLA MM was classified according to the British Society of Transplantation system in low mismatch (LM) (level 1-2) and high mismatch (HM) (level 3-4). Acute rejection (AR) and global or censored graft survival were the outcomes of interest. Recipients were followed up from transplant until death, graft failure or the end of 2020. Results: One thousand sixty-eight kidney transplant recipients were analyzed, 815 (76%) received a DDKT whereas 253 (24%) received an LDKT. From those submitted to DDKT, 95 (12%) had an LM and 720 (88%) had an HM, whereas in LDKT 32 (13%) had an LM and 221 (87%) had an HM. The AR at one year was 9% in the full cohort. Significant risk factors for AR were HM DDKT (OR:2.3, P=0.047) or HM LDKT (OR:5.6, P=0.003) (LM DDKT as reference), calculated panel-reactive antibody (cPRA) ≥5% (OR:1.9, P=0.040) and delayed graft function (DGF), (OR:3.2, P<0.001). Censored graft survival (CGS) at five years was 96% in the full cohort. Independent predictors for censored graft failure (CGF) were HM LDKT (HR:0.2, P=0.046) (LM DDKT as reference), AR (HR:2.7, P=0.008) and DGF (HR:2.2, P=0.017). Global graft survival (GGS) at five years was 91% in the full cohort. Independent predictors for global graft failure (GGF) were HM LDKT (HR:0.2, P=0.042) (LM DDKT as reference), recipient age (HR:1.8, P<0.001) and DGF (HR:1.8, P=0.006). No AR, CGF or GGF episodes were observed in the LM LDKT group. Conclusions: In our cohort, the level of HLA MM increased the risk of AR independently of donor type. Considering short graft survival, our results support the advantage of living donor vs deceased donor even with an increased HLA MM. However, its effect on long-term graft survival remains to be settled, emphasizing the need for further studies on this matter
- Medical Challenges of a Common Variable Immunodeficiency With a TNFRSF13B Gene Mutation in a Simultaneous Kidney and Pancreas Transplant RecipientPublication . Coimbra, Miguel T; Silvano, José; Martins, La SaleteCommon variable immune deficiency (CVID) is a primary immunodeficiency disorder, with hypogammaglobulinemia and increased susceptibility to recurrent infections, autoimmune disorders, granulomatous diseases and malignancy. Among the solid organ transplant (SOT) recipient population, those with primary immunodeficiency disorders under chronic immunosuppression therapy can theoretically be at higher risk of atypical infections, autoimmune complications and disease recurrence with suboptimal long term graft survival, but literature is scarce. Here, we report a 27-year-old female with type 1 diabetes mellitus, complicated with nephropathy that progressed to end-stage renal disease (ESRD), who had a history of a chronic inflammatory response dysregulation, with chronic monoarthritis, persistent elevation of inflammation markers, recurrent infections, low immunoglobulin G (IgG) and A (IgA) serum levels, a slightly decreased population of memory B cells at flow cytometric immunophenotyping, and a confirmed pathological heterozygous mutation in the tumor necrosis factor receptor superfamily 13B (TNFRSF13B), with a suspected diagnosis of CVID. Whilst on hemodialysis, she received a simultaneous kidney and pancreas transplant from a standard criteria donor (SCD), and our induction and maintenance immunosuppression protocol and prophylaxis regimen allowed for a successful transplant with immediate pancreatic function, with no evidence of renal graft rejection upon biopsy in the early post-transplant period, and no novel episodes of serious infectious complications were recorded during a follow-up period of six months
- Accidental Diagnosis of Isolated Persistent Left Superior Vena Cava After an Elective Central Venous Access Procedure for Chronic Hemodialysis: Clinical Implications and Precautions From a Case ReportPublication . Coimbra, Miguel T; Braga, Beatriz; Silva, Adriana; Sousa, Fernanda; Queirós, JoséPersistent left superior vena cava (PLSVC) is the most frequent thoracic venous anatomical variant in the general population. Isolated PLSVC, without formation of the right superior vena cava, is described in 10% of cases of PLSVC only. While it can be associated with congenital heart disease, arrhythmias, and premature death, adult patients with PLSVC are mostly asymptomatic, and the diagnosis is usually accidental. We present the case of a 72-year-old male with end-stage renal disease who was started on urgent hemodialysis through a temporary non-tunneled femoral central venous catheter (CVC) in the SLED (slow low-efficiency dialysis) modality and later remained dependent on hemodialysis. At this stage, placement of a tunneled CVC in the right internal jugular vein was necessary and fluoroscopy guidance was not available. There were no complications during the procedure, but postoperative conventional chest radiography revealed an inadequate positioning of the CVC tip in the left hemithorax, crossing the midline. Subsequently, the diagnosis of PLSVC was obtained by performing a thoracic angio-CT scan, confirming CVC tip positioning inside the PLSVC, and also excluded the presence of cardiac defects or additional anatomical variations of the great vessels of the thorax. Early evaluation for the creation of autologous vascular access was started under our care, and there were no mechanical or other complications associated with hemodialysis sessions during early follow-up after discharge.
- Predicting 6-Month Mortality in Incident Elderly Dialysis Patients: A Simple Prognostic ScorePublication . Lascasas, Josefina; Oliveira, Pedro; J, Malheiro; Campos, Andreia; Correia, Sofia; Cabrita, Antonio; Lobato, Luísa; Fonseca, IsabelAim: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. Methods: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. Results: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0-3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73-0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73-0.85]). Conclusions: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.
- Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function?Publication . Leal Moreira, Carla; Cunha, Liliana; Correia, Sofia; Silva, Filipa; Castro, Ana; Tavares, Joana Manuel; Carvalho, Maria João; Oliveira, José Carlos; Santos, Maria Olivia; Cabrita, Antonio; Rodrigues, AnabelaIntroduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.
- New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the LiteraturePublication . Lousa, Irina; Reis, Flávio; Beirão, Idalina; Alves, Rui; Belo, Luís; Santos-Silva, AliceThe prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients' prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.