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Introduction: Kidney transplant (KT) recipients have a high risk for adverse outcomes from infections, such as COVID-19. Methods: We have retrospectively reviewed all KT recipients with documented COVID-19 between March 1, 2020, and March 15, 2021, and analyzed patients’ characteristics, clinical course, treatment, and outcomes. Results: We identified 123 patients, 72% were male, with a mean age of 54.5±13.0 years. Twenty percent were asymptomatic, 7% had a nosocomial transmission, and 36% of the remainder required hospitalization. Almost all admitted patients received oxygen, 30% required invasive mechanical ventilation (IMV), more than a half had acute kidney injury, with 10% requiring dialysis, and 20% died. Incidence was comparable to that of the Portuguese population, but the mortality rate was almost four times higher (SMR of 3.768 (95% CI:1.723-7.154). Higher body mass index (OR 1.275, P=0.001), lower baseline graft function (OR 0.968, P=0.015), and nosocomial transmission (OR 13.836, P=0.019) were associated with oxygen demand, whereas female gender (OR 3.801, P=0.031) and lower baseline kidney graft function (OR 0.955, P=0.005), but not body mass index, were associated with IMV and/or death. Conclusion: Mortality rate in KT patients was higher than in the general population and lower baseline kidney function was the most consistent marker for adverse outcomes. Resumo Introdução: Os receptores de transplante renal (TR) apresentam um alto risco para desfechos adversos de infecções, tais como a COVID-19. Métodos: Revisamos retrospectivamente todos os receptores de TR com COVID-19 documentada entre 1º de Março de 2020 e 15 de Março de 2021, e analisamos as características, curso clínico, tratamento e desfechos dos pacientes. Resultados: Identificamos 123 pacientes, 72% do sexo masculino, com uma média de idade de 54,5±13,0 anos. Vinte por cento eram assintomáticos, 7% apresentaram transmissão nosocomial, e 36% do restante necessitaram de internação. Quase todos os pacientes internados receberam oxigênio, 30% necessitaram de ventilação mecânica invasiva (VMI), mais da metade apresentou lesão renal aguda, com 10% necessitando de diálise, e 20% foram a óbito. A incidência foi comparável à da população portuguesa, mas a taxa de mortalidade foi quase quatro vezes superior (TMP de 3,768 (IC 95%: 1,723-7,154). Maior índice de massa corporal (OR 1,275; P=0,001), menor função do enxerto basal (OR 0,968; P=0,015), e transmissão nosocomial (OR 13,836; P=0,019) foram associados à demanda de oxigênio, enquanto sexo feminino (OR 3,801; P=0,031) e menor função do enxerto renal basal (OR 0,955; P=0,005), mas não índice de massa corporal, foram associados à VMI e/ou óbito. Conclusão: A taxa de mortalidade em pacientes com TR foi mais elevada do que na população em geral e a função renal basal mais baixa foi o marcador mais consistente para desfechos adversos.

Kidney volume has been proven to be a surrogate marker of nephron mass and renal function. We studied 190 donor and recipient pairs undergoing living donor kidney transplantation at our institution during 9 years. Different metrics of donor kidney volume (DKV) were explored: alone or indexed to recipient's anthropometry, as body surface area (BSA). DKV/BSA (min. 49.7; P33rd 77.7; P67th 95.3; max. 176 cm3 /m2 ) was chosen given its higher correlation with eGFR at 1 year, and recipients were divided according to its tertiles (T). The eGFR at 1 year was lower in T1, when compared with T2 (P = 0.015) and T3 (P

The donors' estimated glomerular filtration rate (eGFR) after living nephrectomy has been a concern, particularly in donors with smaller kindeys. Therefore, we developed this retrospective observational study in 195 donors to determine the ability remaining kidney volume indexed to weight (RKV/W) to predict eGFR at 1 year through multivariate linear regression and to explore this relationship between annual eGFR change from 1 to 4 years postdonation evaluated by a linear mixed model. Comparing RKV/W tertiles (T1, T2, T3), RKV/W was a good predictor of 1-year eGFR which was significantly better in T3 donors. Gender, predonation eGFR, and RKV/W were independent predictors of eGFR at 1-year. In a subgroup with predonation eGFR < 90mL/min/1.73 m2 , a significant prediction of eGFR < 60mL/min/1.73 m2 was detected in males with RKV/W ≤ 2.51cm3 /kg. Annual eGFR (ml/min/year) change from 1 to 4 years was + 0.77. RKV/W divided by tertiles (T1-T3) was the only significant predictor: T2 and T3 donors had an annual eGFR improvement opposing to T1. RKV/W was a good predictor of eGFR at 1 year, independently from predonation eGFR. A higher RKV/W was associated with improved eGFR at 1 year. A decline in eGFR on the four years after surgery was only noticeable in donors with RKV/W ≤ 2.13cm3 /kg. info:eu-repo/semantics/publishedVersion

In simultaneous pancreas-kidney transplantation (SPKT), persistence or recurrence of pancreatic autoantibodies (PAs) has been associated with pancreas graft (PG) autoimmune-driven injury. Our aim was to analyze the impact of PAs on PG survival.Methods. Between January 1, 2000, and December 31, 2017, we studied 139 patients with post-SPKT antieglutamic acid decarboxylase (GAD) autoantibody. Alloimmune (ALI) events were defined as PG rejection and/or de novo donor-specific antibodies (DSA).Hence, 3 groups were defined: patients without ALI events or anti-GAD (n ¼ 42), those with ALI events (n ¼ 14), or those only with autoimmune events (positive for anti-GAD and no ALI events; n ¼ 83). Results. Male sex was predominant (n ¼ 72, 52%). Median age was 35 years (interquartile range: 31-39) and median follow-up was 6-7 years (interquartile range: 4.1-9.2). Regarding anti-GAD positivity post-SPKT (n ¼ 90, 65%), no differences were observed concerning age, sex, anti-HLA antibodies, HLA mismatch number and de novo DSA. ALI events were present in 10% (n ¼ 14). PG survival 15 years post-SPKT was better in patients without immune events (96%) followed by those with ALI (69%) and autoimmune events (63%) (P ¼ .025). Anti-GAD was associated to higher annualized mean Hb1AC (P ¼ .006) and lower mean C-peptide (P ¼ .013). According to pre- and post-SPKT anti-GAD status, conversion from negative to positive was associated to worse (63%) 10-year PG survival (P ¼ .044), compared to persistence of negative (100%) or positive anti-GAD (88%). Anti-islet cell and anti-insulin autoantibodies had no impact. Conclusion. Anti-GAD presence post-SPKT was associated to higher pâncreas disfunction and lower PG survival. De novo anti-GAD seems to offer a particular risk of PG failure. info:eu-repo/semantics/publishedVersion

In this paper we show that Portugal benefitted from comparatively low-interest rates from the 13thcentury onwards, well before the generalised drop in interest rates in Europe. Contrary to the thesis that frontier economies struggle with high-interest rates and scarcity of capital, we find that the country's low and stable interest rates can be explained by its wide availability of land, combined with monetary stability and a favourable institutional network. These conclusions are built upon an entirely new dataset of interest rates and returns on capital for Portugal in the period 1230–1500.

Background HLA mismatching is a well known risk factor for worst outcomes in kidney transplantation. Methods In the present study, HLA antigen and eplet mismatches were determined in 151 living donor-recipient pairs transplanted between 2007 and 2014 and rejection episodes and graft survival were evaluated. Results We found that high HLA-II eplet mismatch load (EpMM ≥ 13, versus low EpMM ≤ 5), was an independent predictor of AMR (adjusted HR = 14.839; P = 0.011), while HLA-II AgMM was not. We also showed that HLA-II EpMM load was a significant better predictor of AMR than AgMM (c-statistic = 0.064; P = 0.023). After discriminating HLA-II into HLA-DR and HLA-DQ loci we demonstrated that high versus low eplet mismatch load for HLA-DR (T3 ≥ 6 versus T = 0–1, p = 0.013) and HLA-DQ (T3 ≥ 7 versus T = 0–1, p = 0.009) are independent predictors for AMR. HLA-II EpMM increased discrimination performance of the classical HLA-II AgMM risk model (IDI, 0.061, 95%CI: 0.005–0.195) for AMR. Compared with AgMM, HLA-II eplet model adequately reclassified 13 of 17 patients (76.5%) with AMR and 92 of 134 patients (68.7%) without AMR (cfNRI, 0.785, 95%CI: 0.300–1.426). Conclusions Our study evidences that eplet-based matching is a refinement of the classical HLA antigen mismatch analysis in LDKT and is a potential biomarker for personalized assessment of alloimmune risk.

To compare mini-incision donor nephrectomy (MDN) with laparoscopic donor nephrectomy (LDN) performed by the same surgical team, regarding short- and long-term outcomes.Three hundred and five patients, who underwent donor nephrectomy in our institution, through an MDN (n = 141) between January 1998-November 2011 and LDN (n = 164) since June 2010-December 2017, were compared.The mean operative time for MDN (120 ± 29 minutes) was not significantly different when compared to LDN (113 ± 34 minutes), but when comparing the first 50 LDN and the 50 most recent, we found a reduction in the duration of the procedure. Laparoscopic donors had a shorter warm ischemia time (229 seconds vs 310 seconds, P = .01), particularly the 50 most recent, hospital stay (4.3 days vs 5.9 days, P .001), and postoperative complications (P = .03). The incidence of graft acute tubular necrosis (ATN) was superior in the MDN (89% vs 25%, P .001), although there was no significant difference regarding first-year serum creatinine (SCr) and glomerular filtration rate (GFR) (SCr 1.38 mg/dL vs SCr 1.33 mg/dL and GFR 63.7 mL/min vs 63.1 mL/min) comparing the 2 groups. Long-term graft survival did not significantly differ between groups. There was also no relationship between postoperative ATN events and long-term graft function.With the growing experience of the high-volume centers and with specialized teams, LDN could be considered the most suitable technique for living donor nephrectomy with better results in short-term results (warm ischemia time, hospital stay, and postoperative complications), without difference in long-term outcomes.

Até 30% dos pares de dador vivo não são transplantados por incompatibilidade do grupo ABO e/ou do sistema Human Leukocyte Antigen (HLA). Os programas de doação renal cruzada surgiram como uma estratégia para tentar ultrapassar estas barreiras. Em Portugal o Programa Nacional de Doação Renal Cruzada (PNDRC) foi legislado em 2010 e o primeiro transplante renal cruzado ocorreu em 2013. Até ao momento foram efetuados 22 transplantes deste tipo. Objetivo: O presente trabalho visa avaliar as caraterísticas e perfil evolutivo dos doentes submetidos a transplante renal cruzado em Portugal. Métodos: Os autores apresentam um estudo observacional retrospetcivo com análise dos respetivos doentes. Resultados: Da amostra total, a maioria dos recetores era do sexo masculino (55%), com idade mediana 53 anos. A poliquistose renal foi a etiologia da doença renal mais comum (18%) e a maioria dos doentes encontrava-se previamente em programa crónico de hemodiálise (68%). Três doentes apresentaram Calculated Panel Reactive Antibody (PRAc) superior a 98% e 10 PRAc superior a 80%. Foi realizada indução de imunossupressão com Anti-Thymocyte Globulin (ATG) em 50% dos doentes e imunomodulação com Rituximab e/ou plasmaferese em 15%. Todos os recetores evoluíram com função imediata do enxerto. Não se registaram complicaçães major, com eventos minor em 15%. Num tempo mediano de follow-up de 2 7 [ 2-46] meses, não se verificou nenhum caso de rejeição celular aguda e a penas um de rejeição humoral. As sobrevidas do dador e recetor foram ambas 100%. Conclusão: A apresentação destes resultados preliminares excelentes visa estimular o aumento do número de pares a incluir no PNDRC e um maior número de transplantes efetuados no programa. Tal como uma parte significativa desta amostra, o transplante renal cruzado pode constituir uma possibilidade para doentes com incompatibilidade do sistema HLA e/ou do grupo ABO. A doação renal cruzada em muito engrandece a doação em vida, oferecendo a pares incompatíveis e selecionados, uma oportunidade de transplantação renal com sucesso.

The thirteenth century was an era of bold constitutional experiments in Europe. During this age, for the first time in history, fiscal constitutions, i.e., limits on the fiscal prerogatives of the state, emerged. In Portugal, this manifested itself as a monetary constitution that prevented the use of the kings’ minting rights and a hidden tax, namely the 1261 Instrumentum Super Facto Monete, which was presented as a contract. It was a genuine monetary constitution insofar as it had the credible commitment of the state and was enforced by the public, via the Cortes until 1369, when it likely outlived its utility for the markets. The beneficial effects of this constitution in reining potential monetary mischief can be observed in the comparatively low nominal interest rates prevalent in Portuguese capital markets.

HLA donor-specific antibodies developed de novo after transplant remain a major cause of chronic allograft dysfunction. Our study main purpose was to determine whether HLA MM, assessed traditionally and by HLA total and AbVer eplet mismatch load (EptMM and EpvMM) assessed with HLAMatchMaker, had impact on dnDSA development after living donor kidney transplantation (LDKT). We retrospectively analysed a cohort of 96 LDKT between 2008 and 2017 performed in Hospital Santo Antonio. Seven patients developed dnDSA-II and EpvMM and EptMM were greater in dnDSA-II group compared to the no dnDSA-II (18.0 ± 8.7 versus 9.9 ± 7.9, p = .041 and 41.3 ± 18.9 versus 23.1 ± 16.7, p = .018), which is not observed for AgMM (2.29 versus 1.56; p = .09). In a multivariate analysis, we found that preformed DSA (HR = 7.983; p = .023), living unrelated donors (HR = 8.052; p = .024) and retransplantation (HR = 14.393; p = .009) were predictors for dnDSA-II (AUC = 0.801; 0.622-0.981). HLA-II EpvMM (HR = 1.105; p = .028; AUC = 0.856) showed to be a superior predictor of dnDSA-II, when compared to AgMM (HR = 1.740; p = .113; AUC = 0.783), when adjusted for these clinical variables. Graft survival was significantly lower within dnDSA-II patient group (36% versus 88%, p < .001). HLA molecular mismatch analysis is extremely important to minimize risk for HLA-II dnDSA development improving outcome and increasing chance of retransplant lowering allosensitization.

From December 2019 to March 2020, China was the epicenter of the SARS‐CoV‐2 infection pandemic, but from that moment on, Europe surpassed China in the number of new cases and deaths related to this novel viral respiratory infection. The emergence of this world pandemic is particularly important for solid organ transplant recipients, who might have an increased risk of mortality, not only due to their chronic immunosuppression status, but also to the cardiovascular risk that correlates with several years of chronic kidney disease. To the extent that there is still a lack of knowledge about the clinical characteristics, evolution, and prognosis of SARS‐CoV‐2 infection in kidney transplant recipients, we will report the first 5 cases diagnosed and followed in our transplant unit, as well as share the therapeutic strategies adopted.

Background and Aims ABO incompatiblitity was considered a barrier to kidney transplant. However, the shortage of available organs for transplantation and the excellent long term results further establish ABO-incompatible (ABOi) as a safe and effective therapeutic strategy. The aim of the present study was to evaluate the outcomes of ABOi transplantation in terms of graft survival and function, rejection episodes and infections complications. Method The authors present a single center retrospective observational study, that include the analyse of 12 patients who underwent ABOi kidney transplantation between November 2014 and July 2019. All patients received Rituximab (375mg/m2) pre-operation and started Tacrolimus, Mycophenolate Mofetil and Prednisolone one week before surgery. Plasmapheresis was done to remove anti-A or B antibodies until their titles were Results : A total of 12 patients were included in the study, 75,0% male with 43 years (IQR 31-50) The most common blood group mismatch was A to O (n=4; 33%). In the first year, 2 of patients (17%) developed acute rejection. The follow-up time was 17 months (IQR 7-36). Five patients (42%) developed infectious complications. None patients developed cytomegalovirus or BK polyomavirus infections. At the end graft and patient survival were 100%. Conclusion ABOi kidney transplantation has become a routine procedure. By this approach, about 30% of living donors who were refused in the past can now donate their kidneys and thereby significantly expand the living donor pool. Immunosuppressive protocol of this Center can be considered safe.

Background and Aims Kidney volume has been proven to be a surrogate marker of nephron mass and renal function in living donors. Although many studies correlate the kidney mass with renal donors’ function after donation, few studies have compared the donated kidney mass with estimated glomerular filtration rate (eGFR) in the kidneýs recipients. The purpose of this study is to examine the relationship between donor kidney volume and post-transplantation graft function by using computerized tomography to obtain renal volumes. Method Clinical data off all donor and recipient pairs undergoing live donor kidney transplantation (KT) at our institution between January 2008 and December 2017 (n=195) were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software and correlate to transplant recipient eGFR. Results All metrics of donor kidney volume (DKV): DKV alone, ADK adjusted for weight, body mass index (BMI) or body surface area (BSA), correlated significantly with eGFR (all with p Significant risk factors for eGFR0% (OR=2.075, P=0.039); higher donor age (OR per unit=1.033, P=0.047); and peritoneal dialysis modality (in comparison with preemptive KT: OR=3.232, P=0.013). Higher (T3) DKV/BSA tercile (in comparison with T1: OR=0.306, P=0.004) was protective of this outcome. Patients that experienced AR at 1-year had significantly lower DKV/BSA, particularly those with acute cellular rejection (ACR). The median follow-up was 4,8 years (IQR: 3.2-7.5). The censored graft survival by DKV/BSA terciles at 10 years were 59,3% for group 1, 91.3% for group 2 and 91.1% for group 3 (figure 3). Conclusion Our study demonstrates that transplantation of donor-recipient pairs with lower DKV/BSA ratio were associated with significantly worse graft function and higher incidence of AR. This data suggests that a larger mass of nephrons remaining adjusted to recipient’s weight seems to predict a better long-term eGFR. This method can be useful in order to identify patients at risk for a low eGFR after KT and, in cases of multiple potential donors, optimize donor selection.

The occurrence of ascites after Renal Transplant (RT) is infrequent, and may be a consequence of surgical or medical complications. Case report: 61 year-old, male, history of arterial hypertension, tongue carcinoma and alcoholic habits 12-20g/day. He had chronic kidney disease secondary to autosomal dominant polycystic kidney disease, without hepatic polycystic disease. He underwent cadaver donor RT in September 2017. He had delayed graft function by surgically corrected renal artery stenosis. He was admitted in January 2018 for ascites de novo, with no response to diuretics. HE had visible abdominal collateral circulation. Graft dysfunction, adequate tacrolinemia, Innocent urinary sediment, mild anemia, without thrombocytopenia. Serum albumin 4.0g / dL. Normal hepatic biochemistry. Peritoneal fluid with transudate characteristics and serum albumin gradient > 1.1. Ultrasound showed hepatomegaly, permeable vascular axes, without splenomegaly. Mycophenolate mofetil was suspended, with reduced remaining immunosuppression. He maintained refractory ascites: excluded infectious, metabolic, autoimmune and neoplastic etiologies. No nephrotic proteinuria and no heart failure. MRI: micronodules compatible with bile cysts. Upper Digestive Tract Endoscopy did not show gastroesophageal varicose veins. Normal abdominal lymphoscintigraphy. He underwent exploratory laparoscopy with liver biopsy: incomplete septal cirrhosis of probable vascular etiology some dilated bile ducts. He maintained progressive RT dysfunction and restarted hemodialysis. The proposed direct measurement of portal pressure was delayed by ascites resolution. There was further recovery of the graft function. Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition.

Background Superior patient and graft survival rates have been attributed to living donor kidney transplant (LDKT) when compared to deceased donor transplantation. The aim of this study was to assess graft survival in a population of LDKT in the last 14 years and the potential impact of some clinical features. Methods A retrospective observational study was conducted, reviewing the records of all patients undergoing LDKT in one center from January 1, 2004, to December 31, 2017. Survival data were evaluated by Kaplan-Meier, log rank test, and Cox regression. Results Two hundred seventy-seven LDKT were performed. The median follow-up time was 4 (0–13) years. Graft loss was observed in 9% of patients; 4 patients died. The overall survival was 97% at year 1, 94% at year 5, and 83% at years 10 and 13. We found a significantly worse graft survival in patients with early vascular complications that required surgical intervention (P = .00) ≥3 HLA MM (P = .01), ≥1 HLA-DR MM (P = .04) and female recipients (P = .01). The negative impact of ≥1 HLA-B MM on survival was borderline (P = .05). After excluding early graft losses secondary to vascular events, ≥1 HLA-A MM and rejection have also implicated a negative impact on survival (P = .04 and .01, respectively). In the multivariate analysis, these variables were still related to inferior survival. Conclusions We observed a good overall graft survival (>80% after 13 years). Possible factors related to poor outcomes suggested by this study were early vascular complications; HLA mismatches; rejection; and, with less certainty, female recipients.

The reduced access of highly-sensitized (HS) patients to kidney transplantation (KTx) is one of the major challenges for transplant community. Therefore, the aim of our study was to estimate the impact of three different vPRA calculations, assessed traditionally and using eplet-based analysis, in donor offers.At 01-01-2020, 157 HS patients are waitlisted for deceased donor KTx and were included in this study. Total vPRA (vPRAt) was calculated considering all patient allosensitization history, using 1 k MFI cut-off. Current vPRA (vPRAc) refers only to the last year SAB assays, using 1 k MFI cut-off. For eplet vPRA (vPRAe) every SAB assay was analyzed by HLAMatchmaker and HLAfusion software. Matching runs have been performed taking vPRA calculation as unacceptable antigens (UAs).All patients had at least one previous sensitizing event and patients with 100% vPRA were predominantly candidates for retransplantation (P 0.001), had higher PRA-CDC (P 0.001), and longer dialysis vintage waiting time (P 0.001). Inter-group movement analysis between vPRA measures showed that 70 (45%), 124 (79%) and 80 (51%) patients were reclassified to a lower group when considering vPRAt to vPRAc, vPRAt to vPRAe and vPRAc to vPRAe, respectively. The median percentage of change in estimated number of match runs needed for 95% probability of finding an acceptable donor was significantly more pronounced by increasing vPRAt intervals, when considering the reclassification from vPRAt to vPRAe (P 0.001) or vPRAc to vPRAe (P = 0.045), while from vPRAt to vPRAc it was not (P = 0.899).Our study demonstrated that the use of total or current vPRA calculations are impairing HS patients, by decreasing transplant probability, leading to dramatically longer waiting times, when compared to eplet based vPRA.

The impact of patient's biological differences in waiting time for kidney transplantation is well known and has been a subject of extensive debate and struggle in transplantation community. Our purpose was to evaluate patient's access to kidney transplantation in Portugal, regarding their degree of allosensitization and blood type. A retrospective cohort study including 1020 candidates for kidney transplantation between 01 January 2010 and 31 December 2011 in transplant unit Centro Hospitalar do Porto was performed. The deceased donor organ offer by blood type decreased with the calculated panel reactive antibody (cPRA) increase for A and B blood groups candidates, while in 0 blood group candidates, a significant reduction in organ offer was only observable in hypersensitized (HS) ones. As a consequence, the median waiting time was also significantly higher in 0 blood group patients, when compared to the remaining groups. However, waiting time increased extensively with cPRA regardless blood type, especially HS patients with increases of 368%, 632%, 486%, and 140% for blood groups A, B, AB, and 0, respectively, when compared to each blood group global median waiting time. Our study shows that important measures need to be undertaken in order to mitigate the huge disadvantage that HS and 0 blood type patients naturally have.

Introduction Immunosuppression has a pivotal role in kidney transplantation. The new prolonged-release formulation of tacrolimus was developed to provide a more convenient once-daily dosing to improve patient adherence. Methods We selected 60 stable kidney transplant recipients who underwent tacrolimus conversion in our unit. Conversion was made on a 1 mg:1 mg basis in 66.7% of patients (n = 40) and on a 1 mg:1.1 mg basis in the remaining 33.3% (n = 20). Clinical and analytical data at conversion and postconversion was analyzed retrospectively to evaluate the efficacy and safety of conversion from tacrolimus twice-daily to once-daily formulation. Results A significant reduction in tacrolimus blood levels requiring an increase in tacrolimus daily dose was observed postconversion. Postconversion tacrolimus blood level reduction >25% was significantly higher in the conversion group 1 mg:1 mg basis ( P = .004). In patients converted 1 mg:1 mg, female sex and higher tacrolimus level at conversion were significant risk factors for a reduction >25% in tacrolimus blood levels after conversion. No significant change was detected between mean glomerular filtration rate at conversion (57 mL/min) and at 3, 6, and 9 months postconversion. Conclusions Once-daily tacrolimus at similar doses to the twice-daily formulation is an efficient and safe treatment option. Conversion made on 1 mg:1.1 mg basis seems advantageous at least in some patients.

BACKGROUND Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available. METHODS We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve risk stratification at time of AMR. Hence, among 467 patients in whom 1 or more graft biopsies were performed between 2008 and 2015, we included 56 with AMR according to Banff '15 criteria. Using concurrent sera, we prospectively identified DSA by single-antigen beads (IgG and C1q) assays. RESULTS Antibody-mediated rejection C4d (+) (n = 28) was associated with preformed DSA (P = 0.007), whereas DSA C1q (+) (n = 25) cases had stronger IgG-DSA (P < 0.001). At AMR, graft function was similar between DSA C1q groups, but in the first year after, it improved in DSA C1q (-), whereas a steady decline was observed in DSA C1q (+) cases, remaining significantly lower from 1 year until 4 years after AMR. DSA C1q (+) was significantly associated with reduced graft survival (P = 0.021), whereas AMR C4d (+) was not (P = 0.550). Importantly, a similar negative impact of DSA C1q (+) on graft survival was observed within AMR C4d (+) (P = 0.040) and (-) (P = 0.036), cases. In multivariable analysis, DSA C1q (+) (hazard ratio, 3.939, P = 0.005) and de novo DSA (hazard ratio, 4.409, P = 0.033) were independent predictors of graft failure, but stronger IgG-DSA was not. Similar results were obtained considering C1q-DSA and IgG-DSA strength as continuous variables. CONCLUSIONS C1q-DSA assessment at AMR can be a valuable tool in detecting patients with higher risk of graft failure.

Chronic-active antibody-mediated rejection (CAABMR) is associated with poor kidney graft survival and has no clear effective treatment. Forty-one cases of CAABMR were detected in indication graft biopsies and evaluated according to current Banff classification. We investigated the impact of concurrent donor-specific antibodies (DSA) and their characteristics, together with non-adherence regarding immunosuppression on CAABMR histopathological phenotypes and prognosis. Twenty-four (59%) patients had detectable DSA at biopsy, with 15 of them being considered non-adherent. Graft function at biopsy was similar in DSA (+) and (−) patients. DSA (+) patients had significantly higher tubulointerstitial inflammation (i and ti) and acute humoral (g+ptc+v+C4d) composite score than DSA (−). DSA (+)/non-adherent cases presented additionally with increased microvascular inflammation (ptc and v), besides having a distinctively lower ah score. C1q DSA strength was higher (P = .046) in non-adherent patients and correlated closely with C4d score (P = .002). Lower graft function and ah score, higher proteinuria and ci + ct score, and, separately per each model, DSA (+) (HR = 2.446, P = .034), DSA (+)/non-adherent (HR = 3.657, P = .005) and DSA (+)/C1q (+) (HR = 4.831, P = .003) status were independent predictors of graft failure. CAABMR with concomitant DSA pose a higher risk of graft failure. Adherence should be evaluated, and histopathological phenotyping and DSA characterization may add critical information.

De novo donor-specific antibodies (dDSA) relevance in simultaneous pancreas-kidney (SPK) transplantation has been scarcely investigated. We analyzed dDSA relationship with grafts outcomes in a long-term follow-up SPK-transplanted cohort. In 150 patients that received SPK transplant between 2000 and 2013, post-transplant anti-human leukocyte antigen (HLA) antibodies were screened and identified using Luminex-based assays in sera collected at 3, 6, and 12 months, then yearly. dDSA were detected in 22 (14.7%) patients at a median 3.1 years after transplant. Pretransplant anti-HLA sensitization (OR = 4.64), full HLA-DR mismatch (OR = 4.38), and previous acute cellular rejection (OR = 9.45) were significant risk factors for dDSA. dDSA were significantly associated with kidney (in association with acute rejection) and pancreas graft failure. In dDSA+ patients, those with at least one graft failure presented more frequently dDSA against class II or I + II (P = 0.011) and locusDQ (P = 0.043) and had a higher median dDSA number (P = 0.014) and strength (P = 0.030). Median time between dDSA emergence and pancreas and kidney graft failure was 5 and 12 months, respectively. Emergence of dDSA increased the risk of grafts failure in SPK-transplanted patients. Full HLA-DR mismatch was associated with dDSA emergence. dDSA characteristics might help identify patients at a higher risk of graft failure.

Donated kidney volume influences post-transplant outcomes and graft survival. We evaluated the relationship between living-donor kidney volume and recipient graft function at 12 months post-transplantation, exploring a volume threshold for a suboptimal graft function, and compared two different formulas of volume estimation. A retrospective analysis of 82 pairs of living-donor kidney transplants was conducted. Donor renal volumes were estimated from computerized tomography scans using the ellipsoid formula and the voxel counting technique. Linear and restricted cubic regression spline was used to analyze the association of volume with graft function. Additionally, we determined the correlation between the two volume estimation formulas and established a correction factor for the ellipsoid formula. Renal volume (adjusted to recipient BSA) had the strongest independent effect (B = 1.65 per 10 ml/m2 increase, p value

Background The relevance of preformed donor specific antibodies (DSA) detected by Luminex assays, with a negative complement-dependent cytotoxicity (CDC) crossmatch, remains unsettled in kidney transplantation (KT). We aimed to analyze the impact of preformed DSA characteristics on kidney graft outcomes. Methods In 462 patients that received a kidney graft in our unit, between 2007 and 2012, pre-transplant sera were analyzed by Luminex screening assay to determine the presence of anti-human leukocyte antigen (HLA) antibodies and single-antigen bead assay [positive if mean fluorescence intensity (MFI) ≥ 1000] to assign anti-HLA specificities. Results Anti-HLA antibodies were present in 95 patients (20.6%), but only 40 (8.7%) had DSA. Antibody-mediated rejection (AMR) at 1-year was higher in patients with DSA (35.0%) than in those without them (0.9%) (P 3000 were significantly associated with AMR occurrence. Receiver operator curves revealed that a MFI of > 4900 in the highest DSA bead had a high sensitivity (85.7%) and that the sum of all DSA beads MFI > 11,000 had a high specificity (92.3%) for AMR prediction. Anti-thymocyte globulin versus basiliximab induction was more frequent in DSA + AMR − (65.4%) versus DSA + AMR + (34.6%) patients (P = 0.072). Five-year censored graft survival was lower in DSA + than in DSA − patients (respectively, 84.8% versus 94.9%, P = 0.006), although survival was only reduced in DSA + AMR + (68.8%) versus DSA + AMR − (96.0%) patients (P = 0.038). Conclusions Preformed DSA is associated with kidney graft loss, in relation with AMR occurrence. DSA strength may be used to improve immunological risk stratification of sensitized patients and their clinical management.

This article presents a benchmark for Portuguese agrarian output for the 1311–20 decade. This benchmark is built from the supply side using the value of church tithes combined with contemporary parish accounts. Two main findings emerge: first, per capita agrarian output was similar in the recently conquered South and the North, hinting that internal migration after the Reconquista led to the equalization of marginal product across the country; second, that Portuguese real per capita agrarian output was above subsistence and higher than that of contemporary England and Wales. This result, which is robust to the assumptions used, confirms that by 1320 Portugal was a “frontier economy” with a high land/labor ratio and a high per capita output. This seems to reinforce the Malthusian theory that the amount of land per person was key in determining living standards. The article discusses the implication of these results for the inequality among nations.

O elevado desenvolvimento industrial, os novos hábitos de consumo e o crescimento populacional tem levado a uma discussão nos vários setores da sociedade acerca da escassez de recursos, das emissões poluentes, e da produção de resíduos. Desta forma, e em contraposição com o modelo económico linear, no qual os produtos após produzidos e consumidos são eliminados, emerge um novo modelo de negócio: “A Economia Circular”. Este é um modelo baseado na reutilização, recuperação, reciclagem e reparação durante o ciclo de conceção e utilização de um produto. Este trabalho pretende fazer um estudo da economia circular na indústria de pasta, papel e cartão. Este foi o setor escolhido porque para além de representar cerca de 8% da produção industrial nacional, tem feito esforços significativos para promover o desenvolvimento ambientalmente sustentável. Assim a dissertação pretende dar a conhecer o ponto de situação do setor pasta, papel e cartão no âmbito da economia circular, fazendo uma comparação ibérica nos anos compreendidos entre 2011 e 2015 através do desenvolvimento de um índice comparativo baseado nos resultados de alguns indicadores ambientais. Também é feito um levantamento das atuais barreiras existentes, bem como a sua respetiva relevância na implementação plena da economia circular através da utilização do método Delphi. Segundo o estudo realizado o setor pasta, papel e cartão em Portugal apresenta um valor de cerca de 26% superior na implementação da economia circular face ao registado no setor em Espanha em 2015, com a peculiaridade que esta diferença tem vindo a diminuir nos últimos cinco anos. Quanto aos resultados do estudo relativo às atuais barreiras na implementação da economia circular no setor pasta, papel e cartão em Portugal, o estudo aponta que, entre outras, as três mais relevantes são a falta de regulamentação de flexibilização e promoção do intercâmbio de subprodutos, a demora no processo de classificação de substâncias como subprodutos e a perceção de que o produto final proveniente da utilização de subprodutos é de qualidade inferior quando comparado com um produto que use matéria prima virgem.

The role of de novo donor-specific anti-human leukocyte antigen (anti-HLA) antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002 and 2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy. All patients had at least one serum collected 1 year before failure (in cases) or end of follow-up (in controls). Cases and controls were very well-matched in several baseline characteristics. Post-transplant anti-HLA antibodies were found in 84% of cases and only 36% of controls (P < .001), with 54% of cases and 16% of controls (P < .001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P < .001) in patients with dnDSA (61% vs 12%), in 53 (47%) patients that had at least one graft biopsy performed during follow-up. dnDSA was a significant risk factor (odds ratio [OR] = 6.06; P = .003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor [hazard ratio (HR) = 2.46; P = .002] of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR = 11.90; P = .006) (HR = 2.30; P = .014) was significantly associated with graft failure. Post-transplant dnDSA was clearly associated with graft loss, particularly if against HLA class II antigens. dnDSA detection should be a tool for post-transplant monitoring of kidney graft recipients, allowing for the identification of those with a higher risk of graft failure.

The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0.7%, 4.0% and 25.5% in NaS, NDSA and DSA patients, respectively (NaS vs. NDSA P=0.004; NaS vs. DSA P0.001; NDSA vs. DSA P0.001). Graft survival was lowest in DSA (78.7%), followed by NDSA (88.0%) and NaS (93.8%) recipients (NaS vs. NDSA P=0.015; NaS vs. DSA P0.001; NDSA vs. DSA P=0.378). Multivariable competing risk analysis confirmed both NDSA (sHR=2.19; P=0.025) and DSA (sHR=2.87; P=0.012) as significant predictors of graft failure. The negative effect of NDSA and DSA on graft survival was significant in patients receiving no induction (P=0.019) or an anti-IL-2 receptor antibody (P0.001), but not in those receiving anti-thymocyte globulin (P=0.852). The recognition of the immunological risk associated with preformed DSA but also NDSA have important implications in patients' risk stratification, and may impact clinical decisions at transplant.

This paper builds on global experience and Guinea-Bissau's specific context to identify an effective nutrition approach along with costs and benefits of key nutrition interventions. It is intended to help guide the selection of the most cost-effective interventions as well as strategies for scaling these up. We estimate that the costs and benefits of implementing 10 nutrition-specific interventions in all regions of Guinea-Bissau would require a public investment of USD 17 million over five years (with about USD 3 million needed to maintain the current coverage of the interventions and USD 14 million needed to expand the coverage to reach 90 percent of the population). The two key conclusions of this paper are, first, that investing in nutrition in Guinea-Bissau is cost-effective based on international standards and, second, that investments in nutrition can generate very substantial health and economic benefits, with one dollar spent on nutrition interventions resulting in about 10 dollars of returns over the productive lives of children covered by high-impact nutrition interventions. Economic productivity could potentially increase by USD 120 million (discounted at 3 percent) over the productive lives of the beneficiaries, with an impressive internal rate of return of 9 percent annually. Theses findings point to a powerful set of nutrition-specific interventions that represent a high cost-effective approach to reducing child malnutrition and stunting in Guinea-Bissau.

Kidney transplantation in children has shown steady improvement in graft survival outcome over the last decades. Using data obtained from the transplantation registry of our center between 1984 and 2012, we assessed the independent determinants of graft failure using the Cox proportional hazards regression. Altogether, 128 recipients younger than 18 years of age at the time of kidney transplantation and who had >3 months graft survival were studied. During 9.95 years of medium follow-up, 27 censored graft failures occurred. Censored graft survival rates at 5, 10, 15, and 20 years post-transplantation were 93%, 82%, 70%, and 63%, respectively. Studied factors included recipient and donor age, recipient gender, dialysis vintage, donor/recipient cytomegalovirus (CMV) serology, panel-reactive antibody percentage, human leukocyte antigen mismatching, previous transplantation number, donor type (deceased vs living donation), cold ischemia time, induction therapy with antithymocyte globulin, occurrence of acute tubular necrosis, and development of acute rejection. Using univariate analysis, the significant predictors for graft-censored failure were adult donor (P < .001), recipient age (P = .035), human leukocyte antigen mismatching (P = .025), antithymocyte globulin induction (P = .03), and development of acute rejection (P < .001). Two factors independently predicted graft-censored failure in multivariate analysis. The odds ratios for graft failure in patients with acute rejection and in children who received an organ of an adult were 3.744 and 4.962, respectively. Pediatric recipients should receive the first priority for allografts from pediatric donors and acute rejection should be meticulously prevented.

Background Kidney transplantation is the treatment of choice for end-stage renal disease, with improved mortality and quality of life compared with dialysis. Desensitization protocols have allowed kidney transplantation of highly sensitized patients, who have a lower probability to receive a matching kidney from a deceased or living donor. The aim of this work was to analyze the post-transplantation period of highly HLA-sensitized patients with positive flow cytometry crossmatch against donor cells. Methods Following an observational, retrospective design, we investigated 16 highly sensitized patients who underwent kidney or kidney-pancreas transplantation, assessing the impact of desensitization protocols and investigating treatment-related complications, graft function, antibody-mediated rejection (AMR) rate, and graft and patient survivals. Results We studied 16 patients with positive flow cytometry crossmatch, who were divided into 2 groups based on whether they were submitted to a desensitization protocol or not. Patients who were desensitized underwent transplantation in later years, had higher immunologic risk (panel reactive antibody peak 62% vs 33%; P = .038), higher percentage of 2nd kidney transplant (75% vs 25%; P = .066), and higher percentage of donor-specific anti-HLA antibodies identified (P = .028). A majority of patients were desensitized with high-dose intravenous immunoglobulin and plasmapheresis, and 5 patients received rituximab. Acute AMR rate was of 38%, and rituximab was associated with fewer episodes of AMR. Only 1 patient had graft failure, due to chronic humoral rejection, and the remaining maintained good graft function (mean serum creatinine value of 1.33 mg/dL). No patient died and few complications related to immunossupression were observed. Conclusions Desensitization protocols were safe and allowed kidney transplantation in highly sensitized patients that probably would never undergo transplantation and gave the opportunity of living-donor transplant to patients with anti-HLA antibodies against the donor.