RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Resumo Introdução Poucos estudos investigaram fatores anteriores à doação que poderiam afetar a recuperação renal após doação renal de doador vivo (LKD, do inglês Living Kidney Donation). Investigamos retrospectivamente o papel da infecção pelo vírus John Cunningham (JCV) e outros fatores de risco pré-doação na magnitude do declínio da função renal após LKD. Métodos: Cargas virais de JCV na urina, taxa de filtração glomerular e pressão arterial foram avaliadas consecutivamente em 60 doadores renais vivos antes da doação. Hipertrofia compensatória subótima foi definida como uma TFGe <60% da TFGe pré-doação. Resultados: LKD (40% infectados pelo JCV) foram acompanhados por 3,2±1,6 anos. Não foi encontrada nenhuma associação entre idade, sexo e hipertensão basal com a TFGe pós-doação no 1º, 2º, 3º e 4º anos <60% da TFGe pré-doação. A recuperação média da TFGe no 3º ano após a doação foi menor em doadores infectados pelo JCV vs doadores não infectados (61,8% vs 71,0%, p=0,006). Conclusão: Levantamos a hipótese de que o JCV pode levar os glomérulos a um estado de hiperfiltração antes da nefrectomia, modulando a magnitude da hipertrofia compensatória após a doação. Por outro lado, o JCV pode limitar a capacidade do rim remanescente de promover a hiperfiltração. É necessário um acompanhamento mais longo para determinar se a virúria por JCV leva, em última instância, a uma menor TFGe ao longo do tempo ou se é um fator de proteção para o rim remanescente.

Abstract Introduction: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. Methods: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. Results: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). Conclusion: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

ABSTRACT Introduction: The severe acute respiratory syndrome coronavirus 2 pandemic caused a negative impact on transplantation worldwide. One of the complexities is the management of the immunosuppression and anti-viral medication in transplant recipients. Herein we describe our experience managing five patients with coronavirus disease 2019 (COVID-19) immediately after kidney transplant. Description: we describe a series of five transplant recipients. Two were submitted to a low immunological risk induction immunosuppression: one developed severe disease, the other developed critical disease. The remaining three were submitted to a high immunologic risk immunosuppression: one developed mild disease, but approximately two months after diagnosis developed moderate COVID-19; another developed severe COVID-19; the remaining patient developed critical illness and perished. Both patients with critical COVID-19 developed bacterial and fungal superinfections in the Intensive Care Unit. All eligible patients were submitted to remdesivir and dexamethasone. The anti-metabolite was reduced or suspended. Despite worsening kidney function during the acute phase, kidney replacement therapy was only needed in one patient and the average serum creatinine at the time of discharge was lower that the pre-COVID-19 nadir. Discussion: There is still no definitive answer on whether solid organ transplant recipients carry a higher risk for morbimortality. Risk factors for the general population can also affect their outcome. The prolonged viral shedding in recipients may explain the irregular evolution of the patient who developed COVID-19 months after the initial diagnosis. The reduction of immunosuppression can be problematic in early post-transplant, but no apparent signs of rejection were noted. Literature addressing this specific context is scarce and studies are needed to clarify the optimal management of these patients.

Severe hypertriglyceridemia is defined as a serum triglyceride level >885mg/dl. It is an uncommon condition associated with serious complications, mainly acute pancreatitis. Treatment includes lifestyle changes, medical therapy and, more recently, extracorporeal apheresis techniques. Herein, we report a case of severe hypertriglyceridemia managed with therapeutic plasma exchange. Our patient presented with severe upper abdominal pain. Bloodwork showed extremely severe hypertriglyceridemia (14871mg/dl) and hypercholesterolemia (1536mg/dl) with only slight elevation of amylase and lipase and no echographic signs of acute pancreatitis. Two sessions of therapeutic plasma exchange were performed, with a mean 3L of plasma treated per session. The triglyceride levels dropped to 2325mg/dl after the first session and to 1207mg/dl after the second. Medical therapy was started, and the patient was discharged a week later. After 36 months of follow-up she remains stable, with triglyceride levels 427mg/dl. In this case therapeutic plasma exchange was an effective and well tolerated treatment for severe hypertriglyceridemia

Resumo Introdução: O hiperparatiroidismo secundário é alvo de várias estratégias terapêuticas, incluindo a utilização de cinacalcet, sendo escassos os resultados referentes aos doentes em diálise peritoneal. Objetivo: Propusemo-nos a avaliar a eficácia da terapêutica com cinacalcet no tratamento dos doentes com hiperparatiroidismo secundário numa unidade portuguesa de diálise peritoneal. Métodos: Estudo retrospectivo que incluiu 27 doentes em diálise peritoneal com hiperparatiroidismo secundário moderado a grave (PTHi > 500 pg/mL) tratados com cinacalcet. Foram analisados os dados demográficos, clínicos e laboratoriais à data de início da terapêutica, ao segundo, quarto e sexto mês e à data do fim do estudo ou da suspensão do mesmo. Resultados: Os doentes estavam em diálise peritoneal há 30,99 ± 16,58 meses e foram tratados com cinacalcet durante 15,6 ± 13,4 meses; 21 (77,8%) doentes apresentaram efeitos adversos gastrointestinais. Os valores de PTHi no início da terapêutica com cinacalcet eram 1145 ± 449 pg/mL. Os últimos valores de PTHi foram 1,131 ± 642 pg/mL. A redução da PTHi foi estatisticamente significativa aos 2 meses após o início do cinacalcet (p = 0,007), mas não nas avaliações subsequentes. Conclusão: Torna-se necessário o desenvolvimento de novas formas de apresentação do cinacalcet, de modo a evitar os efeitos adversos gastrointestinais e melhorar a adesão terapêutica.

Abstract Introduction: Secondary hyperparathyroidism is the target of several therapeutic strategies, including the use of cinacalcet. Most studies were done only in hemodialysis patients, with few data from peritoneal dialysis patients. Objective: The aim of our work was to evaluate the effectiveness of cinacalcet in secondary hyperparathyroidism in a one-center peritoneal dialysis patients. Methods: A retrospective study was performed in 27 peritoneal dialysis patients with moderate to severe secondary hyperparathyroidism (PTHi > 500 pg/mL with normal or elevated serum calcium levels) treated with cinacalcet. Demographic, clinical and laboratory parameters at the beginning of cinacalcet therapy, second, fourth, sixth months after and at the time it was finished were analyzed. Results: Patients were under peritoneal dialysis at 30.99 ± 16.58 months and were treated with cinacalcet for 15.6 ± 13.4 months; 21 (77.8%) patients showed adverse gastrointestinal effects; PTHi levels at the beginning of cinacalcet therapy were 1145 ± 449 pg/mL. The last PTHi levels under cinacalcet therapy was 1131 ± 642 pg/mL. PTHi reduction was statistically significant at 2 months after the beginning of cinacalcet (p = 0.007) but not in the following evaluations. Conclusion: It is necessary the development of new forms of cinacalcet presentation, in order to avoid gastrointestinal effects adverse factors and to improve therapeutic adherence.

Introduction: Kidney transplant (KT) recipients are highly susceptible to urinary tract infections (UTIs). Few data are available regarding the effects of cranberry products in KT recipients. Subjects and methods: This was a randomized double-blind study comparing daily treatment with a cranberry capsule versus a placebo capsule for 6 months. The study protocol was conducted in accordance with the Helsinki Declaration and was approved by the local ethics committee. The study group comprised women undergoing KT for over 1 year, and the exclusion criteria included simultaneous antibiotic UTI prophylaxis. The primary endpoint was UTI occurrence, and the secondary endpoints were the time to first UTI, hospitalization, antibiotic resistance, graft function, immunosuppressive dose changes, and side effects. Results: 55 KT women at a single centre were included as follows: 25 were randomized to the cranberry group, and 30 were assigned to the placebo group. During the study period, 16.4% of the participants presented with a UTI. A diagnosis of UTI within the previous year and KT duration, but not cranberry use (p=0.95) were independent predictors of UTI. Discussion: Cranberry capsules appear to be safe in KT women; however, no clinical efficacy of UTI prophylaxis was demonstrated in this well-designed but underpowered study. Further multicentric and longer trial should be performed to determine cranberry clinical efficacy

Introducão: A doença renal crónica provoca a diminuição da fertilidade. Com a transplantação renal a ferti- lidade é recuperada em poucos meses. Objetivo: Analisar a viabilidade da gravidez no transplante renal e o seu impacto sobre a função renal, as complicações na mulher e no recém-nascido. Métodos: Estudo retro- spectivo das gravidezes ocorridas em transplantadas renais entre 1985 e 2014 numa Unidade de Transplantação, com um follow-up de 12 meses pós gravidez. Resultados: Foram incluídas 18 gravidezes (1 gravidez gemelar) em 13 transplantadas renais com uma média de idades de 31 anos. Destas, 12 gravidezes progrediram, 5 resultaram em aborto espontâneo e 1 em aborto induzido. Apenas uma gravidez se complicou por diabetes gestacional. Ocorreram dois nados-mortos (gravidez gemelar). O peso médio dos 11 recém-nascidos foi de 2,6 kg. Verificou-se uma diminuição significativa da taxa de filtração glomerular estimada aos 3 meses pós parto [p < 0.05], mas 1 ano pós parto a tendência deixou de ser significativa [p> 0.05]. Relativamente à proteinuria, o aumento significativo aos 3 meses pós parto manteve-se aos 12 meses [p < 0.05]. No 3o trimestre verificou-se um aumento significativo da tensão arterial [p < 0.05], que não se manteve aos 12 meses pós parto [p > 0.05]. Nos doentes sob ciclosporina verificou-se uma diminuição dos níveis séricos [p < 0.05] ao longo da gravidez. Não se detetou nenhuma rejeição assim como falência do enxerto durante a gravidez ou no follow-up pós parto. Conclusão: Embora a amostra seja limitada, o número de abortos espontâneos foi superior ao da população geral (24% versus 8 a 20%). O aumento significativo da proteinuria mantido após um ano sugere o aumento do risco de disfunção do enxerto a longo prazo. A diminuição dos níveis séricos de ciclosporina ao longo da gravidez implica uma vigilância mais apertada deste parâmetro neste período

Background: Chronic kidney disease causes decreased fertility. With kidney transplantation, fertility is restored within a few months. Objective: To analyse the feasibility of pregnancy with renal transplantation and its impact on renal function, complications in women and newborns. Methods: Retrospective study of pregnancies that occurred in kidney transplant recipients between 1985 and 2014 in one Transplantation Unit, with a follow-up of 12 months post-partum. Results: Eighteen pregnancies were included (one twin pregnancy) in 13 kidney transplant recipients with an average age of 31 years. Of these, 12 pregnancies progressed, five resulted in miscarriage and one in abortion. Only one pregnancy was complicated by gestational diabetes. There were two stillbirths (twin pregnancy). The average weight of 11 newborns was 2.6 kilograms. There was a significant decrease of estimated glomerular filtration rate at 3 months post-partum [p < 0.05], but a year after delivery, the tendency was not maintained [p > 0.05]. Regarding proteinuria, the significant rise at 3 months was maintained until one year [p <0.05]. A significant increase in blood pressure was observed only on the 3rd trimester [p < 0.05], which did not maintain a year after delivery [p > 0.05]. In patients taking cyclosporine, a decrease in serum levels [p < 0.05] was found throughout the pregnancy. No rejection was detected, as well as graft failure during pregnancy or post-partum follow-up. Conclusion: Although the sample is limited, the number of miscarriages was higher than in the general population (24% versus 8 to 20%). The significant increase of the proteinuria throughout a year suggests a long-term increased risk of graft dysfunction. The decrease in serum cyclosporine levels during pregnancy implies a tighter monitoring of this parameter throughout this period

Introdução: O fator de crescimento do fibroblasto 23 (FGF-23) induz fosfatúria. A sua importância clínica ultrapassa o seu impacto na doença óssea da doença renal, associando-se, segundo alguns autores, à calcificação vascular e à mortalidade. Nos doentes em diálise peritoneal (DP), a função renal residual (FRR) é responsável por uma fracção significativa da excreção do fósforo. O nosso objectivo foi testar se o FGF -23 se relaciona com o débito do filtrado glomerular (DFG) e a excreção de fosfato nesta fase tardia da DRC(5d), focando a sua relação com calcificação vascular. Métodos: O FGF-23 (C terminal) foi medido em 40 doentes prevalentes em DP com função renal residual, com idade de 61.5 (51,0-67,0) anos, em tratamento substitutivo da função renal há 43,5 (23-80,0) meses. Destes doentes, 36,6% eram do sexo feminino 19,5 % tinham diabetes mellitus e 37,5% estavam sob regime de DP automática; 80% iniciaram diálise com DP; apenas 20% estiveram previamente sob outra técnica substitutiva da função renal. Foram exploradas variáveis clínicas relevantes, nomeadamente fosfato dietético, parâmetros ósseos, 25-hidroxivitamina D, magnésio (Mg), DFG, fosfatúria, fração excrecional de fosfato (FEP), albumina, proBNP e o score de calcificação vascular de Adragão. Resultados: Os valores medianos (IQ 25-75) das variáveis séricas foram: FGF-23 1997 (1623-2149) RU/ mL, Mg 0,9 (0,8-1,0) mmol/L, 25-hidroxivitamina D 30 (18-47) nmol/L, cálcio 2,2 (2,0-2,4) mmol/L, fósforo 1,7 (1,3-1-,9) mmol/L, PTH 429 (309-626) pg/mL. O FGF-23 correlacionou-se positivamente com o fósforo sérico (r = 0,39, p = 0,013) e negativamente com o volume de urina (r = -0,48, p = 0,001), fosfatúria (r = -0,594, p < 0,0001) e DFG (r = -0,61, p < 0,0001). No entanto, não se verificou qualquer relação significativa com idade, tempo em terapêutica da substituição da função renal, fósforo dietético, FEP, Mg ou 25-hidroxivitamina D. O grupo com valor elevado de FGF-23 apresentava aumento da FEP. O DFG foi preditor independente de aumento do FGF-23. Por outro lado, nem o FGF-23 nem o rácio baixo FEP/FGF-23 se associaram significati- vamente com o score de calcificação vascular. A albumina (baixa), o magnésio (baixo) e o proBNP (elevado) foram significativamente diferentes em doentes calcificados quando comparados com não calcificados (todos com p < 0,05). Conclusões: No nosso estudo não foi confirmada a associação do FGF-23 com a calcificação vascular. O DFG foi o único preditor independente do aumento de FGF-23 em doentes sob diálise peritoneal com função renal residual. O aumento do FGF-23 sinaliza um processo fosfatúrico ativo, compensatório face à perda de FRR, tal como é expresso pelo aumento da fracção excrecional de fósforo. Poderá alertar para oportuna optimização da dieta e da terapêutica no âmbito do metabolismo fosfocálcico. No entanto a sua associação com calcificação vascular permanece por validar

Introduction and Aims: Fibroblast growth factor 23 (FGF-23) induces phosphaturia. Its clinical impact is beyond mineral bone disease in chronic kidney disease (CKD), being coupled with vascular calcification and mortality. Residual renal function (RRF) is associated with significant capacity to excrete phosphate in peri- toneal dialysis (PD). Besides testing whether FGF-23 is still related with glomerular filtration rate (GFR) and phosphate excretion in this late stage of CKD (5d), we aimed to explore its link with vascular calcification. Subjects and Methods: FGF-23 (C terminal) was measured in forty prevalent PD patients with RRF, aged 61.5 (51.0-67.0) years old, in renal replacement therapy (RRT) for 43.5 (23-80.0) months; 36.6% were female, 19.5% had diabetes mellitus and 37.5% were under automated PD regimen; 80% were on PD first, and only 20% had previous RRT. Relevant variables including dietary phosphate (P) intake, CKD-bone laboratory parameters, serum 25-hydroxyvitamin D, magnesium (Mg) levels, GFR, urinary phosphate, fractional excretion of phosphorus (FEP), albumin, proBNP and Adragão vascular calcification score were explored. Results: Median levels (25-75% range) of serum variables were: FGF-23 1997 (1623-2149) RU/mL, Mg 0.94 (0.8-1.0) mmol/L, 25-hydroxyvitamin D 30 (18-47) nmol/L, calcium 2.2 (2.0-2.37) mmol/L, phosphorus 1.69 (1.30-1.90) mmol/L, PTH 429 (309-626) pg/mL. FGF-23 correlated positively with serum phosphate (r = 0.39, p = 0.013) and negatively with urine volume (r = -0.48, p = 0.001), phosphaturia (r = -0.594, p < 0.0001) and GFR (r =-0.61, p < 0.0001). However, FGF-23 was not significantly correlated with age, total time of RRT, dietary P, FEP, Mg, nor 25-hydroxyvitamin D. High FGF-23 group had higher FEP. GFR was the single inde- pendent predictor of increased FGF-23. On the other hand, neither FGF-23 nor low FEP/FGF-23 ratio were significantly associated with the vascular calcification score. Only albumin (lower), magnesium (lower) and proBNP (higher) levels significantly differed in calcified versus non-calcified patients (all with p < 0.05). Conclusions: In our population, FGF-23 was not associated with vascular calcification. GFR was the single independent predictor of increased FGF-23 in patients with diuresis. Increment of FGF-23 in PD patients signalizes an active endocrine phosphaturic process compensating renal function loss, as expressed by higher fractional excretion of phosphorus. It alerts for dietetic and therapy optimization. However, its link with vascular calcification still lacks validation

Uma transplantada renal de 50 anos, pós menopáusica, com dor óssea, osteoporose, hipercalcémia persistente e níveis elevados de paratormona, apesar de uma razoável função do enxerto renal, foi tratada com bifosfonatos e cinacalcet com início 5 e 6 meses, respectivamente, após a transplantação renal. Verificouse melhoria da densidade óssea medida por DEXA. Foi realizada uma biópsia óssea que revelou um resultado inesperado e preocupante. A doença óssea após a transplantação renal é diferente da DMO-DRC clássica e deve ser gerida de forma distinta. Nalguns casos, como o ilustrado na presente apresentação, justifica-se o diagnóstico invasivo através do recurso à realização de uma biópsia óssea, como é proposto nas orientações da KDIGO.

A 50-year-old post-menopausal recipient of a kidney allograft with bone pain, osteoporosis, persistent hypercalcaemia and elevated parathormone (PTH) levels, despite a satisfactory graft function, was treated with bisphosphonates and cinacalcet starting, respectively, 5 and 6 months after renal transplantation (RT). Sixteen months after treatment, there was improvement of bone mineral density (BMD) measured by dualenergy X-ray absorptiometry (DEXA). A bone biopsy was taken, unveiling a surprising and worrisome result. Post-RT bone disease is different from classic CKD-MBD and should be managed distinctly, including, in some difficult cases, an invasive evaluation through the performance of a bone biopsy, as suggested in the KDIGO guidelines.

Introdução: Os mTOR mostraram-se eficazes na imunossupressão de manutenção em relação à sobrevida do enxerto, mas o seu impacto na sobrevida do doente só recentemente foi avaliado. Neste estudo analisámos todos os doentes transplantados renais na nossa unidade desde 2006/01/01 até 2011/12/31 no que respeita à falência do enxerto e à mortalidade comparando os doentes que foram convertidos para mTOR com os que permaneceram sob inibidor da calcineurina (CNI).População e métodos: Foram avaliados 425 doentes (idade média de 46 ± 13 anos, 60,7% do sexo masculino, 10,1%, diabéticos com tempo médio de seguimento de 44 meses). Durante este período, 123 doentes foram convertidos para mTOR: 8, incluídos no protocolo de um estudo, 13 por neoplasia e 102 por evidência de disfunção crônica do enxerto. Os restantes doentes foram mantidos sob CNI. A sobrevida do enxerto e do doentes foram comparados por Kaplan-Meier e p<0,05 foi considerado significativo.Resultados: Durante o tempo de seguimento, 10 doentes morreram e 28 perderam o enxerto. As características basais foram semelhantes para ambos os grupos, com excepção da idade (os doentes convertidos eram mais velhos, p = 0,012), sexo (masculino mais frequente no grupo mTOR grupo, p = 0,04) e raça (os caucasianos foram mais prevalentes no grupo mTOR, p = 0,012).Não houve diferença entre os dois grupos na sobrevida do enxerto ou do paciente, mesmo após ajuste para idade, sexo, presença de diabetes mellitus ou risco imunológico. Além disso, no subgrupo de doentes com baixo risco imunológico, o uso de mTOR foi associado a uma tendência para a melhoria da sobrevivência dos enxertos renais, embora não estatisticamente significativa (p = 0,06).Conclusão: Apesar do pior prognóstico conferido pelas principais indicações para a conversão de inibidores de mTOR (neoplasia ou disfunção crônica do enxerto) e da idade avançada, não foi encontrada diferença na sobrevida do enxerto ou do doente entre os dois grupos. Em doentes com baixo risco imunológico, o grupo mTOR mostrou uma tendência para melhor sobrevida do enxerto.

Background: Inhibitors of the mammalian target of rapamycin (mTOR) have demonstrated a similar outcome on allograft loss but its impact on patient survival has only recently been evaluated. In this outcome analysis all renal transplants performed at our unit since 1/1/2006 until 12/31/2011, were evaluated. Allograft failure and mortality were compared between patients who were converted to mTOR and those who remained on a calcineurin inhibitor (CNI). Population and Methods: We have evaluated 425 patients (mean age 46±13 years, 60.7% male, 10.1% diabetics, mean follow-up of 44 months). During this period, 123 patients were converted to mTOR: 8 included in a protocol study, 13 due to malignancy and 102 to evidence of chronic pallograft dysfunction. The remaining patients were maintained on a CNI -based regimen. We compared patient and graft survival by Kaplan-Meier analysis and p < 0.05 was considered significant. Results: During the follow-up time, 10 patients died and 28 lost their graft. Baseline characteristics were similar, except for age(converted patients were older, p = 0.012), gender (higher male percentage in mTOR group, p = 0.04) and race (Caucasians were more prevalent in mTOR arm, p = 0.012). There was no difference between the 2 groups on either graft or patient survival, even after adjustment for age, gender, and presence of diabetes mellitus or immunological risk. Moreover, in the subgroup of patients with low immunological risk, the use of mTOR was associated with a trend towards improved renal allograft survival, although not statistically significant (p = 0.06). Conclusion: Despite worse prognosis conferred by the major indications for conversion to mTOR inhibitors (malignancy or chronic allograft dysfunction) and older age, we found no difference on allograft or patient survival between the 2 groups (mTOR versus CNI -based regimen). In patients with low immunological risk, mTOR group showed a trend towards better allograft survival.

Background. Bortezomib, a 26S proteasome inhibitor, is a novel treatment for refractory acute rejection. The main mechanism proposed for its action is the induction of apoptosis of mature plasma cells leading to an interruption of donor-specific antibody production, but other properties may also be involved. Patients and Methods. Four patients presenting with antibody-mediated rejection were treated with bortezomib as rescue therapy. Renal function, proteinuria and anti-HLA antibodies were monitored for 1-3 years. Results. In three cases, graft function recovery and decreased proteinuria occurred, despite the maintenance of donor-specific antibody levels. However, in one case graft function was lost. Side effects were mostly transient. There were no episodes of opportunistic infection. Conclusion. Bortezomib may be effective in antibodymediated rejection by different mechanisms than simply through reducing donor-specific antibody levels. The timing of its introduction and the length of time that donor-specific antibodies have been present may be determinants of its efficacy

In chronic kidney disease patients there are three main stimuli for parathyroid hormone (PTH) secretion by the chief cell in the parathyroid glands: hypocalcaemia, low 1,25(OH)2D3 levels and hyperphosphataemia. FGF23 is a regulator of phosphate and vitamin D metabolism. The discovery of FGF23 actions enlightened our understanding of the development of secondary hyperparathyroidism in CKD patients. The main systemic factors that stimulate FGF23 secretion by the osteocyte in the bone appear to be phosphate load and 1,25(OH)2D3. In the kidney, FGF23 decreases the number of Na/Pi co-transporters IIa and IIc in the tubular cell and promotes phosphaturia. FGF23 also reduces 1,25(OH)2D3 levels by inhibiting, in the kidney, its production by 1-alpha-hydroxylase and stimulating its degradation by 24-hydroxylase. Increase in FGF23 levels has been described in early 2 and 3 CKD stages preceding the decrease of 1,25(OH)2D3 levels and hyperphosphatemia. In this sequence of events, increase of FGF23 in CKD patients seems to be a novel mechanism for the early decline of 1,25(OH)2D3 levels observed in these patients. It was hypothesised that klotho deficiency creates a tissue resistance to FGF23 which is responsible for the increase of FGF23 levels. Reduced renal expression of klotho has been demonstrated in CKD patients preceding FGF23 increase. Chronic kidney disease may be considered a state of klotho deficiency with increase of FGF23 levels. Klotho deficiency may be the initial alteration for the development of phosphate retention and secondary hyperparathyroidism in CKD patients. In this article we review the classic and new pathways involved in the development of secondary hyperparathyroidism in chronic kidney disease and the subsequent actions ensuing from this knowledge. It is possible that, in 3 and 4 CKD stages, an early therapeutic intervention consisting of a low phosphate diet and/or phosphate binders, even in the presence of normophosphataemia, might retard the development of secondary hyperparathyroidism