Is Erythrocytosis More Common After Simultaneous Pancreas Kidney Transplantation? A Single-Center Experience.

Post-transplant erythrocytosis (PTE) is reported in 8% to 22% of kidney transplant recipients. Few studies have evaluated the prevalence of PTE in simultaneous kidney-pancreas transplantation (SPKT). This study aimed to evaluate the prevalence of PTE in a cohort of SPKT and same-donor single kidney transplant patients and find predictive factors for erythrocytosis development. A single-center retrospective cohort study was performed with 65 SPKT recipients and 65 same-donor single kidney transplant patients. Post-transplant erythrocytosis was defined as a hematocrit persistently >51% without a known cause of erythrocytosis. The PTE prevalence was 23.1% and was more frequent in SPKT patients than in single donor patients (38.5% vs 7.7%; P < .001). The mean time for PTE development was 11.2 ± 13.3 months. In the multivariate model, SPKT was the only predictor for PTE development. De novo hypertension was more frequent in the PTE group (P = .002), but there was no difference in stroke and pancreatic or kidney thrombosis occurrence. Post-transplant erythrocytosis is more common after SPKT than after single kidney transplantation. De novo hypertension was more frequent in the erythrocytosis group, but allograft thrombosis rates.

COVID-19 in kidney transplant recipients: what have we learned one year later? A cohort study from a tertiary center / COVID-19 em receptores de transplante renal: o que aprendemos um ano depois? Um estudo de coorte a partir de um centro terciário

Abstract 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.

Antibody-Mediated Rejection in Kidney Transplantation: A Retrospective Study on the Impact of Donor-Specific Antibodies and on the Timing of Diagnosis.

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.

Biologically Unrelated Living Donor for Kidney Transplantation Associated With Higher Acute Rejection Rate but With Similar Graft Survival of a Related Living Donor.

INTRODUCTION: Kidney transplantation (KT) from living donors has been shown to have multiple benefits compared to those from deceased donors. We sought to compare significant graft outcomes, namely acute rejection (AR), graft function, and survival between transplant recipients who received a kidney from living related donor (LRD) and living unrelated donor (LURD). METHODS: Our cohort comprised 198 donor and recipient pairs undergoing living-donor KT at our center over 10 years. The LRD recipients were compared with LURD recipients according to demographic and clinical characteristics, transplant variables (including immunosuppression), graft function, survival, and AR rate. RESULTS: The estimated glomerular filtration rate (eGFR) was similar in both groups over the follow-up time i.e., 60-65 mL/min (p>0.05 over 10 years). Censored graft survival was similar between LRD and LURD recipients (96.9% vs. 98.0% at five years and 87.8% vs. 79.4% at 10 years, respectively; p=0.837). The LURD recipients had a higher incidence of AR, although LURD recipient status was not an independent risk factor for AR. Multivariate analysis showed that human leukocyte antigen (HLA)-DR mismatch (MM) was an independent predictor of AR (hazard ratio (HR) 2.256, p<0.05). Both HLA-A and HLA-B MM did not affect the AR HR between the groups. CONCLUSION:  Graft function and censored graft survival rates were similar between LURD and LRD KT recipients in our study. The AR was higher in LURD recipients, although the LURD recipient status was not an independent risk factor for AR. The HLA-DR MM was an independent predictor of AR, while HLA-A and HLA-B MM did not affect AR HR between groups of patients.

COVID-19 in kidney transplant recipients: what have we learned one year later? A cohort study from a tertiary center.

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.

Why Donors Do Not Donate: A Living Donation Program Experience.

BACKGROUND: A living donor (LD) kidney transplant is the best therapeutic option for end-stage kidney disease. Potential donors must undergo multiple analyses and the rates of live donation can be as low as 8% to 18%. Here, we report on the live kidney donor program in our unit with emphasis on the reasons why potential donors do not proceed to donation. METHODS: We performed a single-center retrospective study of all potential kidney donors with a first LD appointment at Centro Hospitalar Universitário do Porto between January 2016 and December 2020. RESULTS: In our cohort there were 395 potential donors. From the potential donors who finished assessment, 131 were approved for donation and 239 dropped out. After assessment, 104 (28.1%) recipients received a living kidney transplant, 24 of which received a living kidney transplant through the kidney paired exchange program. The individuals who did not proceed to the surgery (n = 239) had a median age of 46.5 years, 64.4% were female, and 34 pairs were ABO-incompatible. The most frequent donor-recipient relationships were spouses, siblings and parents. The 2 most important causes of dropout were due to medical, surgical or psychological contraindications and the donor's voluntary withdrawal. When we evaluated the variables most related to dropout, they were not because of being a spouse and ABO incompatibility. CONCLUSIONS: When compared to other studies, we showed a relatively higher rate of successful live donations, possibly aided by the presence of cross-over transplantation. Targeted education and support at an earlier stage of the donor assessment process may lead to a better engagement and lower probability of early dropout.

Eplet-based virtual PRA increases transplant probability in highly-sensitized patients.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

SARS-CoV-2 infection in kidney transplant recipients: Early report of five cases.

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.

HLA class II eplet mismatch load improves prediction of dnDSA development after living donor kidney transplantation.

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 António. 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.

Psychosocial risk factors for impaired health-related quality of life in living kidney donors: results from the ELIPSY prospective study.

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.

Improving HLA matching in living donor kidney transplantation using kidney paired exchange program.

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.

Remaining kidney volume indexed to weight as a strong predictor of estimated glomerular filtration rate at 1 year and mid-term renal function after living-donor nephrectomy - a retrospective observational study.

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.

Impact of Pancreatic Autoantibodies in Pancreas Graft Survival After Pancreas-Kidney Transplantation.

BACKGROUND: 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 anti-glutamic 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 = 42), those with ALI events (n = 14), or those only with autoimmune events (positive for anti-GAD and no ALI events; n = 83). RESULTS: Male sex was predominant (n = 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 = 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 = 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 = .025). Anti-GAD was associated to higher annualized mean Hb1AC (P = .006) and lower mean C-peptide (P = .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 = .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 pancreas disfunction and lower PG survival. De novo anti-GAD seems to offer a particular risk of PG failure.

Degree of HLA class II eplet mismatch load improves prediction of antibody-mediated rejection in living donor kidney transplantation.

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.

Deleterious effect of anti-angiotensin II type 1 receptor antibodies detected pretransplant on kidney graft outcomes is both proper and synergistic with donor-specific anti-HLA antibodies.

AIM: Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs with or without concomitant DSA on KT outcomes. METHODS: Seventy-six patients transplanted in 2009 were studied. DSA (MFI > 1000) and/or AT1R-abs (>10UI) were detected by solid-phase assays in pre-KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure. RESULTS: At transplant, 48 patients were AT1R-abs (-)/DSA (-), 12 AT1R-abs (+)/DSA (-), 9 AT1R-abs (-)/DSA (+) and 7 AT1R-abs (+)/DSA (+). Incidence of acute rejection at 1-year increased from 6% in AT1R-abs (-)/DSA (-), to 35% in AT1R-abs (+)/DSA (-), 47% in AT1R-abs (-)/DSA (+) and 43% in AT1R-abs (+)/DSA (+) (P < 0.001). No difference in DSA strength and C1q-binding ability was observed between AT1R-abs (-) /DSA (+) and AT1R-abs (+)/DSA (+) patients. Graft survival at 6-years was the lowest in AT1R-abs (+)/DSA (+) (57%), followed by AT1R-abs (+)/DSA (-) (67%), and higher in AT1R-abs (-)/DSA (-) (94%) and AT1R-abs (-)/DSA (+) (89%) patients (P = 0.012). AT1R-abs (+)/DSA (-) (HR = 6.41, 95% CI: 1.43-28.68; P = 0.015) and AT1R-abs (+)/DSA (+) (HR = 7.75, 95% CI: 1.56-38.46; P = 0.012) were independent predictors of graft failure. CONCLUSION: Acute rejection incidence and graft failure were associated with both DSA and AT1R-abs. These results demonstrate a proper negative effect of AT1R-abs on graft outcomes, besides a synergistic one with DSA. Pretransplant AT1R-abs should be acknowledged to better stratify patients' immunological risk.

Detection of Complement-binding Donor-specific Antibodies, Not IgG-antibody Strength Nor C4d Status, at Antibody-mediated Rejection Diagnosis Is an Independent Predictor of Kidney Graft Failure.

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.

Correlations between donor-specific antibodies and non-adherence with chronic active antibody-mediated rejection phenotypes and their impact on kidney graft survival.

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.

Impact on mid-term kidney graft outcomes of pretransplant anti-HLA antibodies detected by solid-phase assays: Do donor-specific antibodies tell the whole story?

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 P<0.001; NDSA vs. DSA P<0.001). 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 P<0.001; 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 (P<0.001), 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.