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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.

Introduction Limited information exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according to DSA status. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according to DSA status after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who had DSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores, DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared to DSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years). Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targeting DSA status according to the time of biopsy. For KB performed less than six months after KT, GS was higher for DSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT, DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

Living kidney donors’ follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors’ psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient’s medical outcomes on their donor’s psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors’ 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering.

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

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.

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.

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.

Background: Porto’s Hospital Centre is one of the most active Portuguese hospitals in renal transplantation (performed since 1983). Although increasingly rare, opportunistic infections in transplanted patients are associated with high mortality rate in kidney transplantation and remain a major diagnostic challenge. Methods: We investigated 2041 cases of hospital admissions (from 2004 to 2012), any time after kidney transplantation. We described the infection location, the diagnostic techniques used and the mortality after the infection. Results: We found 82 cases of opportunistic infection caused by Herpes virus (Zoster and simplex), Cytomegalovirus, Polyomavirus, Aspergilus, Alternaria, Mucorales, Candida, Mycobacterium tuberculosis, Cryptococcus and Pneumocystis. Conclusions: In this article we highlight the important role of histology/cytology in the diagnostic process of these infections. In many cases prompt diagnosis and treatment are necessary to avoid life-threatening complications and may greatly improve prognosis.

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.

Background The inclusion of compatible pairs within kidney paired exchange programs has been described as a way to enhance these programs. Improved immunological matching for the recipient in compatible pair has been described to be a possible benefit. Methods The main purpose of our study was to determine if the introduction of compatible pairs in the Portuguese kidney paired exchange program would result in a better match for these patients, but also to assess if this strategy would increase the number of incompatible pairs with a possible match. We included 17 compatible pairs in kidney paired exchange pool of 35 pairs and performed an in-silico simulation determining HLA eplet mismatch load between the co-registered and matched pairs using HLA MatchMaker, version 3.0. Results Our study showed that the inclusion of fully HLA-A, -B, −DR mismatched compatible pairs within the national Portuguese KEP increased matched rate within ICP (0.71%) and improved HLA eplet matching within compatible pairs. 16 of 17 (94.12%) of the CP obtained one or more transplants possibilities and 13 (81.25%) would have been transplanted with significantly lower HLA class I and class II total and antibody-verified eplet mismatch load (83.9 ± 16.9 vs. 59.8 ± 12.2, P = .002 and 30.1 ± 5.5 vs. 21.2 ± 3.0, P = .003, respectively). Conclusions This strategy is a viable alternative for compatible pairs seeking a better matched kidney and Portuguese KEP program should allow them this possibility.

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.

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.

Detrimental impact of preformed donor-specific antibodies (DSAs) against human leucocyte antigens on outcomes after kidney transplantation are well documented, however, the value of their capacity to bind complement for predicting antibody-mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed to study DSA characteristics (strength and C1q binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen bead (SAB) assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with detectable anti-HLA antibodies). Patients were divided into DSA strength (MFI < vs. ≥ 15 000) and C1q-binding ability. AMR frequency was high (30%) and it increased with DSA strength (P = 0.002) and C1q+ DSA (P < 0.001). The performance of DSA C1q-binding ability as a predictor of AMR was better than DSA strength (diagnostic odds ratio 16.3 vs. 6.4, respectively). Furthermore, a multivariable logistic regression showed that C1q+ DSA was a risk factor for AMR (OR = 16.80, P = 0.001), while high MFI DSAs were not. Graft survival was lower in high MFI C1q+ DSA in comparison with patients with C1q- high or low MFI DSA (at 6 years, 38%, 83% and 80%, respectively; P = 0.001). Both DSA strength and C1q-binding ability assessment seem valuable for improving pretransplant risk assessment. Since DSA C1q-binding ability was a better predictor of AMR and correlated with graft survival, C1q-SAB may be a particularly useful tool.

Background Although donor perceptions of donation have been evaluated in several programs, evaluation of associated recipients has not been as frequent. Purpose Our aim was to evaluate and compare after transplantation, donor and recipient perceptions of donation. Methods After transplantation 35 recipients and 45 donors completed a sociodemographic and a donation perception questionnaire. We applied the Fisher test to descriptive (absolute and relative frequency) data. Results 57.8% of donors were female and 62.9% of recipients male. 53.3% of donors were siblings, 44.5% parents, and 2.2% a daughter. Most recipients (71.9%) thought that the donation was the donors' initiative and 21.9% that it was suggested by medical team. 96.4% responded that it was the donor's wish that determined their decision; 51.4% had serious or some doubts about accepting the option, but for 48.6% it was an easy decision. Among the donors, 88.9% decided by themselves and 8.9% were asked for donation. For 91.1%, their wish was the main reason of the decision, but 8.9% felt a moral obligation; 77.8% thought it was an easy decision, and 17.8% hesitated a little 84.4% were not worried about their future health. Conclusions Altruistic motivations were predominant in both groups. Most recipients thought that the motivation for donation was self-determined, a finding that agreed with donor perceptions. Perceptions about the quality of and changes in emotional relationship were the same in both groups. Donors and recipients referred to the donation process as positive, but there were some negative emotions and perceptions.

Cryptococcal infection has been increasing among immunosuppressed population. We report three cases of Cryptococcus neoformans infection in immunosuppressed patients – two renal transplanted and one with lupus nephritis. Early infection (

We present a case of a renal transplant patient with surgical wound infection 20 1days after kidney transplant.

Transpl Int. 2007 Mar;20(3):291-6. Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus. Pedroso SL, Martins LS, Sousa S, Reis A, Dias L, Henriques AC, Sarmento AM, Cabrita A. Nephrology Department, Hospital Geral de Santo António, Porto, Portugal. sofiapedroso@sapo.pt Abstract The aim of our paper is to describe an unusual pulmonary toxicity of sirolimus (SRL) in a kidney transplant recipient. We present a 34-year-old woman with a second renal transplantation, complicated with steroid-resistant acute rejection and chronic allograft dysfunction. Two years after initiating SRL, she presented complaints of progressive dyspnoea, nonproductive cough, chest pain and low-grade fever of 1 month duration. She had chronic allograft nephropathy and slight elevation of lactic dehydrogenase levels. After exclusion of common reasons of this condition, a computed tomography (CT) of the thorax and bronchoscopy was performed, revealing ground-glass opacification with polygonal shapes on CT and an opaque appearance with numerous macrophages on bronchoalveolar lavage. The alveolar macrophages stained positive by Periodic acid-Schiff. Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug-induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients' clinical and radiological status. PAP resolved within 3 months without further therapy. PAP is a very rare complication of SRL therapy with only a few cases described. Withdrawal of SRL with conversion to another immunosuppressant seems to be an appropriate procedure in this condition. PMID: 17291222 [PubMed - indexed for MEDLINE

Objective In kidney transplantation, the impact of delayed graft function (DGF) on long-term graft and patient survival is controversial. We examined the impact of DGF on graft and recipient survival by accounting for the possibility that death with graft function may act as a competing risk for allograft failure. Study design and Setting We used data from 1281 adult primary deceased-donor kidney recipients whose allografts functioned at least 1 year. Results The probability of graft loss occurrence is overestimated using the complement of Kaplan–Meier estimates (1-KM). Both the cause-specific Cox proportional hazard regression model (standard Cox) and the subdistribution hazard regression model proposed by Fine and Gray showed that DGF was associated with shorter time to graft failure (csHR = 2.0, P = 0.002; sHR = 1.57, P = 0.009), independent of acute rejection (AR) and after adjusting for traditional factors associated with graft failure. Regarding patient survival, DGF was a predictor of patient death using the cause-specific Cox model (csHR = 1.57, P = 0.029) but not using the subdistribution model. Conclusions The probability of graft loss from competing end points should not be reported with the 1-KM. Application of a regression model for subdistribution hazard showed that, independent of AR, DGF has a detrimental effect on long-term graft survival, but not on patient survival.

Pancreas-kidney transplantation (PKT) may significantly improve quality of life (HRQOL) in patients with type 1 diabetes. We have assessed the changes felt by PKT patients, using the Gastrointestinal Quality of Life Index (GIQLI) and EuroQol-5D questionnaires. Patients were asked to compare how their HRQOL had changed from pre-transplantation to the last visit. The 60 men and 66 women enrolled had a mean follow-up of five yr; 84.1% with both grafts, 15.9% with one graft functioning. In all domains of EuroQol-5D scores improved after PKT, as well as the visual analogue scale health state (from 38% to 84%, p < 0.001; effect size 3.34). In GIQLI, physical function was felt better after PKT than before (14.83 3.86 vs. 7.86 4.43, p < 0.001; effect size 1.68); the same was observed for psychological status, social function, and GI complaints. Concerning the burden of medical treatment, the score significantly improved (from 1.31 to 3.63, p < 0.001, effect size 2.02). The rate of unemployed patients decreased after PKT (from 50.8% to 36.5%, p < 0.001). Multivariate analysis showed that having only one functioning graft was associated with worse HRQOL scores (B = 5.157, p = 0.015). In conclusion, for all assessed domains, patients reported a significant improvement in HRQOL after PKT. Maintenance of the two grafts functioning predicted higher improvement of HRQOL scores.

Introduction Serum creatinine (SCr) alone does not allow for the early diagnosis of delayed graft function (DGF) following kidney transplantation (KTx). Objective, design and methods The diagnostic utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum leptin, malondialdehyde (MD.A), and cystatin C (CysC) for the early detection of DGF was previously evaluated by our group in a prospective cohort study of 40 consecutive adults undergoing KTx. Because no single biomarker achieved adequate sensitivity or specificity for practical purposes, this study was designed to evaluate the combined use of new markers with SCr. Urine and blood samples were collected 8-to-12 h after KTx (day-1). Logistic regression was used to combine the biomarkers, and receiver operating characteristic curves and areas under the curve (AUC–ROC) were generated. Results Eighteen recipients developed DGF (dialysis requirement during the first post-transplant week). On day-1, the AUC for SCr to predict DGF was 0.73, 0.88 for uNGAL, 0.90 for MDA, 0.76 for leptin, and 0.91 for CysC. Adding new biomarkers to SCr enhanced the performance of DGF prediction, and the best combination was achieved with SCr, MDA, and CysC (AUC = 0.96, sensitivity = 100%; specificity = 86%). Conclusion A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC.

Context and Objective Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF = dialysis requirement during the first post-transplant week) and acute rejection. Study Design Repeated-measures prospective study. Material and Methods Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used. Results At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n = 18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC = 0.73). On day-1, serum leptin predicted DGF (AUC-ROC = 0.76) with a performance slightly better than serum creatinine (AUC-ROC = 0.72), even after correcting for BMI (AUC-ROC = 0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC = 0.86) improved. Conclusions Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.

It remains controversial whether dialysis modality prior to SPKT (simultaneous pancreas-kidney transplantation) affects the outcome. We analyzed outcomes in type 1 diabetic patients undergoing SPKT, comparing peritoneal dialysis (PD) and hemodialysis (HD) groups: 119 had been on HD; 39 on PD. They were comparable except regarding dialysis time, higher in HD patients (30 ± 23 vs. 21 ± 15 months, P = 0.003). Thrombosis-driven relaparotomy was more frequent in PD patients (12.8% vs. 1.7%, P = 0.014). Pancreas loss due to infection was higher in PD patients (12.8% vs. 3.4%, P = 0.042). Thrombosis-related kidney loss was more frequent in PD patients (5.1%, vs. 0% in HD patients, P = 0.058). Thirteen deaths occurred, more within the PD group (17.9% vs. 5%; P = 0.011), being infection the leading cause (13.5%, vs. 1.7% in HD patients, P = 0.010). Patient survival was inferior in PD patients. Besides PD, cardiovascular disease and graft failure were independent predictors of patient death. In conclusion, PD patients more frequently complicated with intra-abominal infection leading to pancreatic loss and with renal thrombosis, with adverse impact on survival. As a PD first strategy in end-stage renal disease patients is generally associated with good outcomes, these gloomier results after SPKT urge for careful adjustment of infection and thrombosis prophylactic protocols in PD patients.

Type 1 diabetes recurrence has been documented in simultaneous pancreas-kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow-up (maximum 138 months), 43.8% of patients were positive (from pre-transplant or after recurrence) for at least one autoantibody - the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti-insulin (8.6%) and anti-islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C-peptide levels, and a higher number of HLA-matches. Analyzing the sample divided into four groups according to pre-/post-transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C-peptide levels. Positivity for these autoantibodies pre-transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody-positive SPKT is a matter of concern, which deserves further attention.

Introduction. Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled.Methods. Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes.Results. Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%,P=0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1,P<0.01), HLA mismatches>3 (HR = 10.2,P=0.03), and antibody positivity for anti-HLA class II (HR = 5.1,P=0.04) or class I/II (HR = 13.8,P<0.01) were independent predictors of graft loss.Conclusions. Allosensitization against HLA classII±Iafter transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.