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Background The rising prevalence of end-stage renal failure in the elderly has led to an increased number of kidney transplantations in older individuals. While age does not solely determine transplant eligibility, frailty in elderly recipients significantly impacts post-transplant outcomes, particularly within the first year. Methods The RETRAITE (REnal TRAnsplantIon ouTcome in Elderly recipients) study, a single-center retrospective cohort study at Grenoble Alpes University Hospital (France), examined kidney transplant recipients aged 70 years and above transplanted between 2015 and 2020. The composite primary endpoint was defined as either of any hospital stay exceeding 40 days, death and/or return to dialysis within the first post-transplant year. The study explored risk factors for recipient and graft survival, rejection, hospitalizations over 40 days, and severe infections during the initial post-transplant year. Results Over six years, 149 patients aged 70 years or older received transplants. Eleven patients died, and seven returned to dialysis within the first year, corresponding to a 1-year graft survival rate of 87.9%. At 1 year, 49 patients (33%) met the composite endpoint. There was a significant association between the composite endpoint and curative anticoagulation [odds ratio (OR) 5.20; P  < .001], peripheral arteriopathy (OR 3.14; P  < .001) and delayed graft function (OR 8.24; P  < .001). This cohort then was merged with a cohort of 150 younger kidney transplanted patients and we confirmed these results. Time on dialysis, prolonged cold ischemia and donor age contributed to higher morbidity and mortality. Conversely, preemptive and living donor transplants were associated with lower morbidity and mortality. Conclusions In this cohort aged over 70 years, age alone did not statistically correlate with increased morbidity and mortality. Variables related to grafts and donors, especially curative anticoagulation, were linked to poorer outcomes, emphasizing the favorable impact of preemptive and living donor transplants on morbidity and mortality in elderly patients. [ABSTRACT FROM AUTHOR]

Impacts of ischemic time (IT) on pediatric heart transplant outcomes are multifactorial. We aimed to analyze the effect of prolonged IT on graft loss after pediatric heart transplantation. We hypothesized that graft survival with prolonged IT has improved across eras. Patients <18 years old in the Pediatric Heart Transplant Society database were included (N=6,765) and stratified by diagnosis and era (1993-2004, 2005-2009, and 2010-2019). Severe graft failure (SGF) was defined as death, retransplant, or need for mechanical circulatory support in the first 7 days post-transplant. Descriptive statistical methods were used to compare differences between patient characteristics and IT. Kaplan-Meier survival analysis compared freedom from graft loss, rejection, and infection. Multivariable analysis was performed for graft loss and SGF (hazard and logistic regression modeling, respectively). Diagnoses were cardiomyopathy (N = 3,246) and congenital heart disease (CHD; N = 3,305). CHD were younger, more likely to have an IT ≥4.5 hours, and more likely to require extracorporeal membrane oxygenation or mechanical ventilation at transplant (all p < 0.001). Median IT was 3.6 hours (interquartile range 2.98-4.31; range 0-10.5). IT was associated with early graft loss (HR 1.012, 95% CI 1.005-1.019), but not when analyzed only in the most recent era. IT was associated with SGF (OR 1.016 95%CI 1.003-1.030). Donor IT was independently associated with an increased risk of graft loss, albeit with a small effect relative to other risk factors. Graft survival with prolonged IT has improved in the most recent era but the risk of SGF persists. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to compare the outcomes of living donor kidney transplantation with blood- and non-blood-related donors across multiple facilities. Previous reports comparing these outcomes have been single-center studies. As the donors were the recipients’ spouses in all cases with non-blood-related donors, we independently compared the outcomes of wife-to-husband (WTH) and husband-to-wife (HTW) transplantations. No previous multicenter studies have compared transplant outcomes between spouses in this manner. Methods This retrospective study used a shared database including 643 cases from 6 facilities that primarily used tacrolimus as a calcineurin inhibitor. We used propensity score matching to compare the outcomes of transplantations with blood- and non-blood-related donors and those of WTH and HTW transplantations. Results Of the 643 cases examined, 381 and 262 had blood- and non-blood-related donors, respectively. All non-blood-related donor cases had spouses as donors. After propensity score matching, 84 cases each were selected from the blood- and non-blood-related donor groups for comparison, with no significant intergroup difference in the time to graft loss. Among the 262 interspousal transplantations, 91 were HTW transplantations and 171 were WTH transplantations. Following propensity score matching, 58 cases each were selected from the WTH and HTW groups for comparison, with no significant intergroup difference in the time to graft loss. Conclusions In this large multicenter retrospective study, no significant differences were observed in the outcomes of transplantations with blood- and non-blood-related donors. Furthermore, no significant differences were observed in the outcomes of WTH and HTW cases. Many centers that use tacrolimus-based four-drug immunosuppressive therapy may have similar trends as those observed in this study, making our findings significant for planning transplantation involving kidneys donated from patients’ spouses.

Introduction: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. Methods: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy‐proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. Results: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. Conclusion: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology. [ABSTRACT FROM AUTHOR]

Introduction: Kidney allograft survival has increased significantly in the past few decades. However, the more potent immunosuppression has also resulted in a higher incidence of infections including BK virus nephropathy (BKVN). The profile of kidney transplant (KT) recipients including age, basic kidney disease, comorbidities, dialysis vintage, and type of kidney donor in India is different from that of high-income countries. There are very few studies on the incidence and outcomes of BKVN from India. We studied the incidence, clinical features, and the impact of a screening strategy on patients with BKVN at our center. Materials and Methods: This was a single-center retrospective record-based study. We screened the medical records of all KT recipients at our center from March 2012 to December 2020 for patients who were diagnosed with BKVN. We compared the incidence of BKVN before and after the implementation of a proactive screening strategy in 2017. Results: From March 2012 to December 2020, a total of 212 KTs were performed at our center. Twenty-eight patients were diagnosed to have BKVN at this time. The incidence of BKVN in our study was 13.2%. The incidence of BKVN before routine screening was initiated at our center was 11.3% whereas it was 13.6% after routine screening was initiated. Graft loss from BKVN was 7.14%. Conclusion: The incidence of BKVN at our center is higher than previously reported in India; however, the rate of graft loss is low. A proactive screening strategy using nucleic acid test may allow early detection of BKVN and may have a beneficial impact on graft outcomes.

Rejection is one of the major factors affecting the long-term prognosis of kidney transplantation, and timely recognition and aggressive treatment of rejection is essential to prevent disease progression. RBPs are proteins that bind to RNA to form ribonucleoprotein complexes, thereby affecting RNA stability, processing, splicing, localization, transport, and translation, which play a key role in post-transcriptional gene regulation. However, their role in renal transplant rejection and long-term graft survival is unclear. The aim of this study was to comprehensively analyze the expression of RPBs in renal rejection and use it to construct a robust prediction strategy for long-term graft survival. The microarray expression profiles used in this study were obtained from GEO database. In this study, a total of eight hub RBPs were identified, all of which were upregulated in renal rejection samples. Based on these RBPs, the renal rejection samples could be categorized into two different clusters (cluster A and cluster B). Inflammatory activation in cluster B and functional enrichment analysis showed a strong association with rejection-related pathways. The diagnostic prediction model had a high diagnostic accuracy for T cell mediated rejection (TCMR) in renal grafts (area under the curve = 0.86). The prognostic prediction model effectively predicts the prognosis and survival of renal grafts (p

Background: The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging. Methods: We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations. Results: The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples. Conclusion: This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. Methods: We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. Results: We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. Conclusion: The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pretransplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status. [ABSTRACT FROM AUTHOR]

T‐cell mediated rejection (TCMR), de novo anti‐HLA donor‐specific antibodies (dnDSAs) and ensuing antibody‐mediated rejection (ABMR) reduce kidney transplantation (KT) survival. The immunomodulatory effects of 25‐hydroxyvitamin D [25(OH)D] could be beneficial for KT outcomes. We aimed to evaluating the association between 25(OH)D levels, the development of dnDSAs, clinical TCMR and ABMR, and graft survival. This single center retrospective study included 253 KT recipients (KTRs) transplanted without preformed DSA between 2010 and 2013. We measured 25(OH)D in successive serum samples: at KT (M0) and M12 for the entire cohort, and additionally at M24 and/or M36 when sera were available. We assessed graft outcomes up to 5 years post‐KT. The proportion of KTRs having sufficient 25(OH)D at KT (M0) was high (81.4%) and then dropped at M12 (71.1%). KTRs with sufficient 25(OH)D at M0 experienced less clinical TCMR (HR, 0.41; 95% CI, 0.19–0.88 in multivariate analysis). A sufficient 25(OH)D at M12 was independently associated with a longer dnDSA‐free survival (HR, 0.34; 95% CI, 0.17–0.69). There was no association between 25(OH)D and clinical AMBR. Studying the KTRs with 25(OH)D measurements at M12, M24 and M36 (n = 203), we showed that 25(OH)D sufficiency over the 3 first‐years post‐KT was associated with a longer graft survival in multivariate analyses (HR, 0.39; 95% CI, 0.22–0.70). To our knowledge, this study is the first showing an association between 25(OH)D sufficiency post‐KT and dnDSA occurrence in KTRs. Moreover, we reinforce previously published data showing an association between 25(OH)D, TCMR and graft survival in KT. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. Methods We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). Results A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P  = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119–4.910, P  = .024) independently of other histologic and clinical variables. Conclusions In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies. [ABSTRACT FROM AUTHOR]

Introduction: Kidney allograft survival has increased significantly in the past few decades. However, the more potent immunosuppression has also resulted in a higher incidence of infections including BK virus nephropathy (BKVN). The profile of kidney transplant (KT) recipients including age, basic kidney disease, comorbidities, dialysis vintage, and type of kidney donor in India is different from that of high-income countries. There are very few studies on the incidence and outcomes of BKVN from India. We studied the incidence, clinical features, and the impact of a screening strategy on patients with BKVN at our center. Materials and Methods: This was a single-center retrospective record-based study. We screened the medical records of all KT recipients at our center from March 2012 to December 2020 for patients who were diagnosed with BKVN. We compared the incidence of BKVN before and after the implementation of a proactive screening strategy in 2017. Results: From March 2012 to December 2020, a total of 212 KTs were performed at our center. Twenty-eight patients were diagnosed to have BKVN at this time. The incidence of BKVN in our study was 13.2%. The incidence of BKVN before routine screening was initiated at our center was 11.3% whereas it was 13.6% after routine screening was initiated. Graft loss from BKVN was 7.14%. Conclusion: The incidence of BKVN at our center is higher than previously reported in India; however, the rate of graft loss is low. A proactive screening strategy using nucleic acid test may allow early detection of BKVN and may have a beneficial impact on graft outcomes. [ABSTRACT FROM AUTHOR]

Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT. Any BKPyV DNAemia was defined as a single BKPyV DNA of ≥1000 copies/mL. Severe BKPyV DNAemia was defined as two consecutive BKPyV DNA of ≥10,000 copies/mL. Cumulative incidences were investigated using the Aalen–Johansen estimator, and the risk factors were investigated in Cox proportional hazard models. The incidence of any BKPyV DNAemia and severe BKPyV DNAemia was 21% (18–25) and 13% (10–16) at one year post-KT, respectively. Recipient age > 50 years (aHR, 1.72; 95% CI 1.00–2.94; p = 0.049), male sex (aHR, 1.96; 95% CI 1.17–3.29; p = 0.011), living donors (aHR, 1.65; 95% CI 1.03–2.74; p = 0.045), and >3 HLA-ABDR mismatches (aHR, 1.72; 95% CI 1.01–2.94; p = 0.046) increased the risk of severe BKPyV DNAemia. Any BKPyV DNAemia was associated with an increased risk of graft function decline (aHR, 2.26; 95% CI 1.00–5.12; p = 0.049), and severe BKPyV DNAemia was associated with an increased risk of graft loss (aHR, 3.18; 95% CI 1.06–9.58; p = 0.039). These findings highlight the importance of BKPyV monitoring post-KT. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion after kidney transplantation may increase the risk of sensitization and development of de novo human leukocyte antigen (HLA) donor-specific antibodies (DSAs). This study aimed to evaluate whether blood transfusion during the first year after kidney transplantation influences the development of de novo DSAs and clinical outcomes of kidney transplantation recipients. Methods: This retrospective cohort study included nonsensitized first-time kidney transplantation recipients at Tianjin First Central Hospital from 2010 to 2022. The incidence of de novo DSA development and clinical outcomes between the groups were compared. Luminex single antigen beads were used to monitor DSAs. Results: Of the 538 non-HLA-sensitized kidney transplantation recipients included in the study, 164 patients who received at least one unit of leukoreduced red blood cell transfusion within the first year (the transfused group), whereas the remaining 374 patients received no blood transfusion (the non-transfused group). Our analysis showed that there was a significant difference in the development of de novo DSAs and de novo anti-class I HLAAb between the two groups. Indeed, the transfused recipients had a higher serum creatinine and lower estimated glomerular filtration rate (eGFR) at 1-, 6-, and 12-month (all p > 0.05) after transplantation. Futhermore, a higher incidence of CMV infection, antibody-mediated rejection (AMR), hyper acute rejection (HAR), and delayed graft function (DGF) was identified in the transfused group (all p < 0.05). The graft survival was lower in the transfused group compared with patients in the non-transfused group (P 0.002). Blood transfusion posttransplantation was a risk factor for de novo DSAs development but not an independent predictive factor for AMR and graft loss (odds ratio = 2.064 [1.243-3.429], p = 0.005). Conclusions: Our study showed that blood transfusion after transplantation is associated with the occurrence of de novo DSAs increasing an immunological risk for poor clinical outcomes for kidney transplantation recipients. [ABSTRACT FROM AUTHOR]

Background Metabolic syndrome (MetS) is prevalent in patients with end-stage kidney disease, and kidney transplantation is expected to modify the metabolic status. However, whether changes in metabolic status at the time of transplantation affect recipient outcomes remains unclear. Methods We analyzed 4187 recipients registered in a nationwide prospective cohort from 2014 to 2020. MetS was defined as the presence of three or more components of the metabolic syndrome. Patients were classified based on the pre- and post-transplant MetS status: MetS-free, MetS-developed, MetS-recovered and MetS-persistent. Study outcomes were occurrence of death-censored graft loss and a composite of cardiovascular events and death. Results Among recipients without pre-transplant MetS, 19.6% (419/2135) developed post-transplant MetS, and MetS disappeared in 38.7% (794/2052) of the recipients with pre-transplant MetS. Among the four groups, the MetS-developed group showed the worst graft survival rate, and the MetS-persistent group had a poorer composite event-free survival rate. Compared with the MetS-free group, the MetS-developed group was associated with an increased risk of graft loss [adjusted hazard ratio (aHR) 2.35; 95% confidence interval (CI) 1.17–4.98] and the risk of graft loss increased with increasing numbers of dysfunctional MetS components. MetS-persistent was associated with increased risks of cardiovascular events and death (aHR 2.46; 95% CI 1.12–5.63), but changes in the number of dysfunctional MetS components was not. Conclusion Kidney transplantation significantly alters the metabolic status. Newly developed MetS after transplantation was associated with an increased risk of graft loss, whereas persistent MetS exposure before and after transplantation was associated with increased risks cardiovascular events and patient survival. [ABSTRACT FROM AUTHOR]

Background: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. Patients and methods: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. Results: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). Conclusion: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course. [ABSTRACT FROM AUTHOR]

Background: Early graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 weeks and 1 year after kidney transplantation. Methods: We measured 21 inflammatory biomarkers 10 weeks after transplantation in 699 patients who were transplanted between 2009 and 2012 at Oslo University Hospital, Rikshospitalet, Norway. Low-grade inflammation was assessed with predefined inflammation scores based on specific biomarkers: one overall inflammation score and five pathway-specific scores. Surveillance or indication biopsies were performed in all patients 6 weeks after transplantation. The scores were tested in Cox regression models. Results: Median follow-up time was 9.1 years (interquartile range 7.6-10.7 years). During the study period, there were 84 (12.2%) death-censored graft losses. The overall inflammation score was associated with long-term kidney graft loss both when assessed as a continuous variable (hazard ratio 1.03, 95% CI 1.01-1.06, P = 0.005) and as a categorical variable (4th quartile: hazard ratio 3.19, 95% CI 1.43- 7.10, P = 0.005). In the pathway-specific analyses, fibrogenesis activity and vascular inflammation stood out. The vascular inflammation score was associated with inflammation in biopsies 6 weeks and 1 year after transplantation, while the fibrinogenesis score was associated with interstitial fibrosis and tubular atrophy. Conclusion: In conclusion, a systemic inflammatory environment early after kidney transplantation was associated with biopsy-confirmed kidney graft pathology and long-term kidney graft loss. The systemic vascular inflammation score correlated with inflammatory findings in biopsies 6 weeks and 1 year after transplantation. [ABSTRACT FROM AUTHOR]

Background: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV. Aims: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR). Methods: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non‐invasive imaging. Results: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR =.11, p <.001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p <.001) whereas Group B showed minimal change on protocol annual biopsy (−.02, p =.80). After SVR, most patients were followed non‐invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (−.19, p <.001). Conclusion: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR. [ABSTRACT FROM AUTHOR]

Background: Antibody-mediated rejection (ABMR) significantly affects transplanted kidney survival, yet the macrophage phenotype, ontogeny, and mechanisms in ABMR remain unclear. Method: We analyzed post-transplant sequencing and clinical data from GEO and ArrayExpress. Using dimensionality reduction and clustering on scRNA-seq data, we identified macrophage subpopulations and compared their infiltration in ABMR and non-rejection cases. Cibersort quantified these subpopulations in bulk samples. Cellchat, SCENIC, monocle2, and monocle3 helped explore intercellular interactions, predict transcription factors, and simulate differentiation of cell subsets. The Scissor method linked macrophage subgroups with transplant prognosis. Furthermore, hdWGCNA, nichnet, and lasso regression identified key genes associated with core transcription factors in selected macrophages, validated by external datasets. Results: Six macrophage subgroups were identified in five post-transplant kidney biopsies. M1-like infiltrating macrophages, prevalent in ABMR, correlated with pathological injury severity. MIF acted as a primary intercellular signal in these macrophages. STAT1 regulated monocyte-to-M1-like phenotype transformation, impacting transplant prognosis via the IFNγ pathway. The prognostic models built on the upstream and downstream genes of STAT1 effectively predicted transplant survival. The TLR4-STAT1-PARP9 axis may regulate the pro-inflammatory phenotype of M1-like infiltrating macrophages, identifying PARP9 as a potential target for mitigating ABMR inflammation. Conclusion: Our study delineates the macrophage landscape in ABMR post-kidney transplantation, underscoring the detrimental impact of M1-like infiltrating macrophages on ABMR pathology and prognosis.

BackgroundThe routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging.MethodsWe investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.ResultsThe assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%–0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.ConclusionThis is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.

Background. Sinus floor elevation is considered a safe procedure to properly augment the height of the edentulous crest. Often, complications may arise due to multiple causes and can lead to a poor outcome of the graft and implant’s osseointegration. A careful surgical approach, a good knowledge of possible obstacles, and careful treatment planning can reduce the risks of complications, as well as their impact on the surgical outcome. This study aims to make a literature review of 40 articles, analyzing the incidence and type of complications related to maxillary sinus graft surgeries and graft materials. Material and methods. A total of 40 articles published between 2015 and 2021 were selected for a systematic literature review on maxillary sinus floor complications. The studies were selected from 2 different internet databases: PubMed and Science Direct. The sinus lift complications were counted and their incidence was organized upon the surgical technique and the timing of occurrence (intraoperative, postoperative). It was also analyzed if the graft material influences the complication rate. Results. In a group of 1757 sinus augmentation surgeries performed on 1605 patients, 363 complications were found. Sinus membrane perforation occurred in 242 cases, 29 procedures resulted in partial or total graft loss, there were 26 postoperative cases of sinusitis, 24 sinus infections, 16 wound dehiscence, 6 bleeding complications, 5 lost implants, and 2 oro-antral fistulas. Conclusion. Sinus lift complications are sometimes inherent circumstances of the procedures, but they can also be prevented through an accurate technique and preoperative plan. The type of bone graft does not influence the incidence of surgical complications.

BackgroundEarly graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 weeks and 1 year after kidney transplantation.MethodsWe measured 21 inflammatory biomarkers 10 weeks after transplantation in 699 patients who were transplanted between 2009 and 2012 at Oslo University Hospital, Rikshospitalet, Norway. Low-grade inflammation was assessed with predefined inflammation scores based on specific biomarkers: one overall inflammation score and five pathway-specific scores. Surveillance or indication biopsies were performed in all patients 6 weeks after transplantation. The scores were tested in Cox regression models.ResultsMedian follow-up time was 9.1 years (interquartile range 7.6-10.7 years). During the study period, there were 84 (12.2%) death-censored graft losses. The overall inflammation score was associated with long-term kidney graft loss both when assessed as a continuous variable (hazard ratio 1.03, 95% CI 1.01-1.06, P = 0.005) and as a categorical variable (4th quartile: hazard ratio 3.19, 95% CI 1.43-7.10, P = 0.005). In the pathway-specific analyses, fibrogenesis activity and vascular inflammation stood out. The vascular inflammation score was associated with inflammation in biopsies 6 weeks and 1 year after transplantation, while the fibrinogenesis score was associated with interstitial fibrosis and tubular atrophy.ConclusionIn conclusion, a systemic inflammatory environment early after kidney transplantation was associated with biopsy-confirmed kidney graft pathology and long-term kidney graft loss. The systemic vascular inflammation score correlated with inflammatory findings in biopsies 6 weeks and 1 year after transplantation.

Background: Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. Methods: This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. Results: Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03–2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20–3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. Conclusions: Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic. [ABSTRACT FROM AUTHOR]

Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019. Luminex IgG single antigen beads (SAB)and C1q-SAB assays (One Lambda) were used. C1q-binding dnDSA was identified in 32/69 (46.4%) of the patients. Significantly higher MFI values were observed in C1q-positive DSA (18,978 versus 5840, p < 0.001). Renal graft biopsies were performed in 43 of the kidney transplant recipients (62.3%) with allograft dysfunction. Antibody-mediated rejection (ABMR) was detected in 29/43 (67.4%) of the patients. The incidence of ABMR was similar among patients with C1q-binding and non-C1q-binding DSA (51.7% vs. 48.3%, p = 0.523). Graft loss occurred in 30/69 (43.5%) of the patients at a median time of 82.5 months (IQR 45–135) from DSA detection. C1q-binding DSA was present in more patients who experienced graft loss (53.1% vs. 35.1%, p = 0.152). Higher MFI values and inferior clinical outcomes occurred in most of the kidney transplant recipients with C1q-binding dnDSA. [ABSTRACT FROM AUTHOR]

Abstract Background Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). Case presentation A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. Conclusions Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Abstract Background In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. Methods We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000–2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC + . Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. Results Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03–1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01–14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. Conclusions Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT.

The relationship between blood transfusion following kidney transplantation (KT) and the development of de novo donor-specific antibodies (dnDSA) is controversial. This was investigated by conducting a meta-analysis of studies on patients who underwent KT with or without blood transfusion, and by evaluating the effect of post-KT blood transfusion on clinical outcomes of kidney transplant recipients. Relevant studies in the PubMed, EMBASE, and Cochrane Library databases were identified from inception to July 1, 2022. Two reviewers independently extracted data from the selected articles and estimated study quality. A fixed effects or random effects model was used to pool data according to the heterogeneity among studies. Data included in the meta-analysis were derived from 11 studies with a total of 19,543 patients including 6191 with and 13,352 without blood transfusion postKT. We assessed the pooled associations between blood transfusion and occurrence of dnDSA and clinical outcomes of transplant recipients. Blood transfusion was strongly correlated with the development of dnDSA (relative risk [RR] 1.40, 95% confidence interval [CI]: 1.17-1.67; P < 0.05). Patients with blood transfusion had a higher risk of developing anti-human leukocyte antigen (HLA) class I dnDSA than non-transfused patients (RR = 1.75, 95% CI: 1.14-2.69; P < 0.05) as well as significantly higher rates of antibody-mediated rejection (AMR) (RR = 1.41, 95% CI: 1.21-2.35; P < 0.05) and graft loss (RR = 1.75, 95% CI: 1.30-2.35; P < 0.05). There were no statistically significant differences between the two groups in the development of anti-HLA antibodies, anti-HLA class II dnDSA, and anti-HLA class I and II dnDSA; delayed graft function; T cell-mediated rejection; acute rejection; borderline rejection; or patient death. Our results suggest that blood transfusion was associated with dnDSA development in KT recipients. The findings of this systematic review also suggest that post-KT blood transfusion recipients have a higher risk of AMR, and graft loss compared with non-transfused patients. Evidence from this meta-analysis indicates that the use of blood transfusion post-KT is associated with a significantly higher risk of immunological sensitization. More and higher quality results from large randomized controlled trials are still needed to inform clinical practice. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections and the resulting disease, coronavirus disease 2019 (COVID‐19), have spread to millions of persons worldwide. Many vaccines have been developed; however, their efficacy in pediatric solid organ transplant recipients is yet to be determined. Methods: This is a prospective observational, non‐interventional single‐center study on the safety and efficacy of a COVID‐19 vaccine (BNT162b2) in pediatric kidney transplant recipients. The primary aim of this study was to evaluate immunogenicity according to SARS‐CoV‐2‐specific neutralizing antibody titer after two vaccine doses. The secondary aims were to investigate the safety of the vaccines, solicited local and systemic adverse reactions, incidence of COVID‐19 post‐vaccination, and effects on transplant graft function. Baseline investigations were conducted on pediatric renal transplant recipients, and recruited participants were advised to have the Comirnaty® mRNA vaccine according to protocol. Results: A total of 48 patients (male, n = 31, 64.6%; female, n = 17, 35.4%), median age 14 [12–16] years were included, and all received two doses of the vaccine. The vaccine had a favorable safety and side‐effect profile. The S‐antibody titer of all patients ranged between.4 and 2,500 U/ml and was > 50 U/ml in 89% of the patients. No difference in the measured antibody immune response was noted between infected and uninfected children. No major side effects were reported. Conclusion: The vaccine had a favorable safety profile in 12‐ to 15‐year‐old kidney transplant recipients, producing a greater measured antibody response than that in older transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Early post‐kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all‐cause graft loss and mortality. Methods: We estimated 5‐year post‐KT (n = 151 170; SRTR) BMI trajectories using an adjusted mixed effects model. We estimated long‐term mortality and graft loss risks by 1‐year BMI change quartile (decrease [1st quartile]: change < −.07 kg/m2/month; stable [2nd quartile]: −.07 ≤ change ≤.09 kg/m2/month; increase [3rd, 4th quartile]: change >.09 kg/m2/month) using adjusted Cox proportional hazards models. Results: BMI increased in the 3 years post‐KT (.64 kg/m2/year, 95% CI:.63,.64) and decreased in years 3–5 (−.24 kg/m2/year, 95% CI: −.26, −.22). 1‐year post‐KT BMI decrease was associated with elevated risks of all‐cause mortality (aHR = 1.13, 95% CI: 1.10–1.16), all‐cause graft loss (aHR = 1.13, 95% CI: 1.10–1.15), death‐censored graft loss (aHR = 1.15, 95% CI: 1.11–1.19), and mortality with functioning graft (aHR = 1.11, 95% CI: 1.08–1.14). Among recipients with obesity (pre‐KT BMI≥30 kg/m2), BMI increase was associated with higher all‐cause mortality (aHR = 1.09, 95% CI: 1.05–1.14), all‐cause graft loss (aHR = 1.05, 95% CI: 1.01–1.09), and mortality with functioning graft (aHR = 1.10, 95% CI: 1.05–1.15) risks, but not death‐censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all‐cause graft loss (aHR =.97, 95% CI:.95–.99) and death‐censored graft loss (aHR =.93, 95% CI:.90–.96) risks, but not all‐cause mortality or mortality with functioning graft risks. Conclusions: BMI increases in the 3 years post‐KT, then decreases in years 3–5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post‐KT. [ABSTRACT FROM AUTHOR]

Background. Sinus floor elevation is considered a safe procedure to properly augment the height of the edentulous crest. Often, complications may arise due to multiple causes and can lead to a poor outcome of the graft and implant’s osseointegration. A careful surgical approach, a good knowledge of possible obstacles, and careful treatment planning can reduce the risks of complications, as well as their impact on the surgical outcome. This study aims to make a literature review of 40 articles, analyzing the incidence and type of complications related to maxillary sinus graft surgeries and graft materials. Material and methods. A total of 40 articles published between 2015 and 2021 were selected for a systematic literature review on maxillary sinus floor complications. The studies were selected from 2 different internet databases: PubMed and Science Direct. The sinus lift complications were counted and their incidence was organized upon the surgical technique and the timing of occurrence (intraoperative, postoperative). It was also analyzed if the graft material influences the complication rate. Results. In a group of 1757 sinus augmentation surgeries performed on 1605 patients, 363 complications were found. Sinus membrane perforation occurred in 242 cases, 29 procedures resulted in partial or total graft loss, there were 26 postoperative cases of sinusitis, 24 sinus infections, 16 wound dehiscence, 6 bleeding complications, 5 lost implants, and 2 oro-antral fistulas. Conclusion. Sinus lift complications are sometimes inherent circumstances of the procedures, but they can also be prevented through an accurate technique and preoperative plan. The type of bone graft does not influence the incidence of surgical complications. [ABSTRACT FROM AUTHOR]

Introduction: Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods: Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results: Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14–3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29–5.43, P 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41–7.38; P 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

Background: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). Case presentation: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. Conclusions: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. [ABSTRACT FROM AUTHOR]

Background: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. Methods: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000–2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC +. Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. Results: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03–1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01–14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. Conclusions: Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT. [ABSTRACT FROM AUTHOR]

Background/aim: We compared long-term outcomes after kidney transplantation (KTx) in patients with and without congenital anomalies of the kidney and urinary tract (CAKUT). Materials and methods: KTx recipients (KTRs) with CAKUT in 1980-2016 were identified; their hard copy and electronic medical records were reviewed and compared to a propensity-score-matched control group (non-CAKUT) from the same period. The primary outcomes were graft loss or death with a functioning graft; secondary outcomes included posttransplant urinary tract infections (UTIs) and biopsy-proven rejection (BPR). Results: We identified 169 KTRs with CAKUT and 169 matched controls. Median follow-up was 132 (IQR: 75.0-170.0) months. UTIs were more common in CAKUT patients compared to non-CAKUT group (20.7% vs 10.7%; p = 0.01). Rates of BPR were similar between the two groups. In Kaplan-Meier analysis, 10-year graft survival rates were significantly higher in the CAKUT group than in the non-CAKUT group (87.6% vs 69.2%; p < 0.001), while patient survival rates were similar. In multivariate Cox regression analyses, CAKUT (HR: 0.469; 95% CI: 0.320-0.687; p < 0.001) and PRA positivity before transplantation (HR: 3.756; 95% CI: 1.507-9.364; p = 0.005) predicted graft loss. Conclusions: Graft survival in KTRs with CAKUT appears superior to KTRs without CAKUT. Transplant centers should develop multidisciplinary educational and social working groups to support and encourage CAKUT patients with kidney failure to seek for transplants. [ABSTRACT FROM AUTHOR]

Introduction: The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome. Methods: We investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants. Results: There was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (<6.5k), graft survival was not significantly different. Discussion: Our results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation. [ABSTRACT FROM AUTHOR]

The impact of preformed and de novo HLA‐DP antibodies after renal transplantation remains controversial and unclear. To address the clinical relevance of HLA‐DP antibodies on the outcomes in renal transplantation, we performed a random effect model meta‐analysis through a systematic review from inception to December 31, 2021. The outcome was graft loss or acute rejection. Finally five articles were identified as our inclusion criteria. The study which reported 1166 patients included in the final meta‐analysis of de novo HLA‐DP antibodies after transplantation showed an increased risk of graft loss or acute rejection (OR = 3.6, 95% CI = 1.6–8.10, P = 0.002, I2 = 52%). In the subgroup study, we established that patients with HLA‐DP DSA after renal transplantation had a 8.85‐fold increased risk of graft loss or acute rejection compared with patients without HLA‐DP DSA (p = 0.003).While as for HLA‐DP NDSA after renal transplantation, 2.73‐fold increased risk of graft loss or acute rejection compared with patients without HLA‐DP antibodies (p = 0.04). Besides, the studies which reported 487 patients included in the final meta‐analysis of preformed HLA‐DP antibodies did not show an increased risk of graft loss or acute rejection (OR = 4.55, 95% CI = 0.79–26.16, P = 0.09, I2 = 57%). The results of our meta‐analysis suggested that de novo HLA‐DP antibodies especially de novo HLA‐DP DSA had a significant deleterious impact on the renal transplant risk of graft loss or acute rejection, while preformed HLA‐DP antibodies had a no significant deleterious impact on the risk. The routine detection of HLA‐DP antibodies after renal transplantation seems to be very important and may be as one of noninvasive biomarker‐guided risk stratification. [ABSTRACT FROM AUTHOR]

Utilizing data from the largest European organ transplantation organization, we developed KTOP, the first European online risk tool for predicting kidney transplantation outcomes. The tool provides comprehensive guidance for patient and clinician decision-making regarding transplantation both before and after a donor is identified. European kidney donation shortages mandate efficient organ allocation by optimizing the prediction of success for individual recipients. To develop the first European online risk tool for kidney transplant outcomes on the basis of recipient-only and recipient plus donor characteristics. We used individual recipient and donor risk factors and three outcomes (death, death with functioning graft [DWFG], and graft loss) for 32 958 transplants within the Eurotransplant kidney allocation system and the Eurotransplant senior program between January 2006 and May 2018 in eight European countries to develop and validate a risk tool. Cox proportional-hazards models were used to analyze the association of risk factors with overall patient mortality, and proportional subdistribution hazard regression models for their association with graft loss and DWFG. Prediction models were developed with recipient-only and recipient-donor risk factors. Sensitivity analyses based on time-specific area under the receiver operating characteristic curve (AUC) with leave-one-country-out validation were performed and calibration plots were generated. The 10-yr cumulative incidence rate was 37% for mortality, 12% for DWFG, and 41% for graft loss. In recipient-donor models the leading risk factors for mortality were recipient diabetes (hazard ratio [HR] 10.73), retransplantation (HR 3.08 per transplant), and recipient age (HR 1.08). Effects were similar for DWFG. For graft loss, diabetes (subdistributional HR [SHR] 1.32), increased donor age (SHR 1.02), and prolonged cold ischemia time (SHR 1.02) had increased SHRs. All p values were <0.001. Previously identified risk factors for outcomes following kidney transplants allow for outcome prediction with 10-yr AUC values of up to 0.81. Using European data, we estimated individual risks to predict the success of kidney transplants and support physicians in decision-making. An online tool is now available (https://riskcalc.org/ktop/) for predicting kidney transplant outcomes both before and after a donor has been identified. [ABSTRACT FROM AUTHOR]

BackgroundVitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far.MethodsWe conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs.ResultsCompared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912−0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977−1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01−1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98−1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99−1.02) and mortality (OR = 1.01, 95% CI: 0.99−1.02).ConclusionBaseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs.

Background: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. Patients and methods: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. Results: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). Conclusion: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.

Focal segmental glomerular sclerosis is a pattern of histological damage of the kidney. The most common clinical manifestation is proteinuria, however, it can frequently progress to full nephrotic syndrome. Glucocorticosteroids are the first line of treatment and, in case of resistance, calcineurin inhibitors are used. In some patients, despite treatment, focal segmental glomerular sclerosis leads to end-stage renal disease, in which organ transplantation is the only therapeutic option. In several cases, relapse occurs in the transplanted organ. The following paper presents a case report of a patient treated for focal segmental glomerular sclerosis since the age of 21, who developed end-stage renal failure after seven years of disease despite immunosuppressive treatment. Although there was a significant risk of recurrence, it was decided to transplant a kidney from a family donor -- the patient's mother. From about one week after transplantation, progressive deterioration of graft function was observed. [ABSTRACT FROM AUTHOR]

IntroductionThe type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.MethodsWe investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants.ResultsThere was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (

Abstract Background Frailty predicts adverse post-kidney transplant (KT) outcomes, yet the impact of frailty assessment on center-level outcomes remains unclear. We sought to test whether transplant centers assessing frailty as part of clinical practice have better pre- and post-KT outcomes in all adult patients (≥18 years) and older patients (≥65 years). Methods In a survey of US transplant centers (11/2017–4/2018), 132 (response rate = 65.3%) centers reported their frailty assessment practices (frequency and specific tool) at KT evaluation and admission. Assessment frequency was categorized as never, sometime, and always; type of assessment tool was categorized as none, validated (for post-KT risk prediction), and any other tool. Center characteristics and clinical outcomes for adult patients during 2017–2019 were gleaned from the transplant national registry (Scientific Registry of Transplant Recipients). Poisson regression was used to estimate incidence rate ratios (IRRs) of waitlist outcomes (waitlist mortality, transplantation) in candidates and IRRs of post-KT outcomes (all-cause mortality, death-censored graft loss) in recipients by frailty assessment frequency. We also estimated IRRs of waitlist outcomes by type of assessment tool at evaluation. All models were adjusted for case mix and center characteristics. Results Assessing frailty at evaluation was associated with lower waitlist mortality rate (always IRR = 0.91,95%CI:0.84–0.99; sometimes = 0.89,95%CI:0.83–0.96) and KT rate (always = 0.94,95%CI:0.91–0.97; sometimes = 0.88,95%CI:0.85–0.90); the associations with waitlist mortality rate (always = 0.86,95%CI:0.74–0.99; sometimes = 0.83,95%CI:0.73–0.94) and KT rate (always = 0.82,95%CI:0.77–0.88; sometimes = 0.92,95%CI:0.87–0.98) were stronger in older patients. Furthermore, using validated (IRR = 0.90,95%CI:0.88–0.92) or any other tool (IRR = 0.90,95%CI:0.87–0.93) at evaluation was associated lower KT rate, while only using a validated tool was associated with lower waitlist mortality rate (IRR = 0.89,95%CI:0.83–0.96), especially in older patients (IRR = 0.82,95%CI:0.72–0.93). At admission for KT, always assessing frailty was associated with a lower graft loss rate (IRR = 0.71,95%CI:0.54–0.92) but not with mortality (IRR = 0.93,95%CI:0.76–1.13). Conclusions Assessing frailty at evaluation is associated with lower KT rate, while only using a validated frailty assessment tool is associated with better survival, particularly in older candidates. Centers always assessing frailty at admission are likely to have better graft survival rates. Transplant centers may utilize validated frailty assessment tools to secure KT access for appropriate candidates and to better allocate health care resources for patients identified as frail, particularly for older patients.

Background: Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. Methods: This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. Results: Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03–2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20–3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. Conclusions: Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.

Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019. Luminex IgG single antigen beads (SAB)and C1q-SAB assays (One Lambda) were used. C1q-binding dnDSA was identified in 32/69 (46.4%) of the patients. Significantly higher MFI values were observed in C1q-positive DSA (18,978 versus 5840, p < 0.001). Renal graft biopsies were performed in 43 of the kidney transplant recipients (62.3%) with allograft dysfunction. Antibody-mediated rejection (ABMR) was detected in 29/43 (67.4%) of the patients. The incidence of ABMR was similar among patients with C1q-binding and non-C1q-binding DSA (51.7% vs. 48.3%, p = 0.523). Graft loss occurred in 30/69 (43.5%) of the patients at a median time of 82.5 months (IQR 45–135) from DSA detection. C1q-binding DSA was present in more patients who experienced graft loss (53.1% vs. 35.1%, p = 0.152). Higher MFI values and inferior clinical outcomes occurred in most of the kidney transplant recipients with C1q-binding dnDSA.

Electrical burns are considered as the most devastating and one of the most common causes of burn admissions worldwide. It is cited as the 4th most frequent cause of admission among burn units worldwide. Approximately 1–20% of admission in the Philippine General Hospital Alfredo T. Ramirez Burn center is secondary to electrical burn. This is an analytic retrospective cohort study identifying factors associated with mortality, pneumonia, skin graft loss, and amputation among electrical burn patients admitted to the PGH ATR Burn Center from January 2013 to December 2019. Survival analysis was performed using Log Rank test and Cox proportional hazard regression model. Data analysis was performed using STATA 14. In this study, significant predictors of amputation identified are the following: compartment syndrome, fasciotomy, number of operations, and involvement of trunk and perineum. Significant predictors of mortality include use of metal rod, compartment syndrome, fasciotomy, total body surface area (TBSA), number of operations and age. The use of metal rod pertains to a patient holding a metal conductor near the power line. Significant predictors of pneumonia include the use of metal rod, time of injury, compartment syndrome, fasciotomy, TBSA, number of operations and time of injury to admission/referral and age. Compartment syndrome secondary to high voltage electrical burn injury is strongly associated with amputation by as much 2.13 fold. Patients who have compartment syndrome have 84.5 fold risk of mortality compared to those patients without compartment syndrome. Every day which passes from time of injury to admission predispose patients to develop pneumonia by 0.42 times. Incidence of electrical burns remain to be high in the Philippines due to the country’s rapid rate of industrialization. Preventive measures such as use of proper protective equipment and public health campaigns should be done to reduce the incidence of electrical burns.

ObjectiveThe role of m6A modification in kidney transplant-associated immunity, especially in alloimmunity, still remains unknown. This study aims to explore the potential value of m6A-related immune genes in predicting graft loss and diagnosing T cell mediated rejection (TCMR), as well as the possible role they play in renal graft dysfunction.MethodsRenal transplant-related cohorts and transcript expression data were obtained from the GEO database. First, we conducted correlation analysis in the discovery cohort to identify the m6A-related immune genes. Then, lasso regression and random forest were used respectively to build prediction models in the prognosis and diagnosis cohort, to predict graft loss and discriminate TCMR in dysfunctional renal grafts. Connectivity map (CMap) analysis was applied to identify potential therapeutic compounds for TCMR.ResultsThe prognostic prediction model effectively predicts the prognosis and survival of renal grafts with clinical indications (P< 0.001) and applies to both rejection and non-rejection situations. The diagnostic prediction model discriminates TCMR in dysfunctional renal grafts with high accuracy (area under curve = 0.891). Meanwhile, the classifier score of the diagnostic model, as a continuity index, is positively correlated with the severity of main pathological injuries of TCMR. Furthermore, it is found that METTL3, FTO, WATP, and RBM15 are likely to play a pivotal part in the regulation of immune response in TCMR. By CMap analysis, several small molecular compounds are found to be able to reverse TCMR including fenoldopam, dextromethorphan, and so on.ConclusionsTogether, our findings explore the value of m6A-related immune genes in predicting the prognosis of renal grafts and diagnosis of TCMR.

Background: As the prevalence of obesity increases globally, appreciating the effect of donor and recipient (DR) obesity on graft outcomes is of increasing importance. Methods: In a cohort of adult, kidney transplant recipients (2000–2017) identified using the SRTR, we used Cox proportional hazards models to examine the association between DR obesity pairing (body mass index (BMI) >30 kg/m² ), and death-censored graft loss (DCGL) or all-cause graft loss, and logistic regression to examine risk of delayed graft function (DGF) and ≤30 days graft loss. We also explored the association of DR weight mismatch (>30 kg, 10-30 kg (D>R; D