Urinary Dickkopf 3 Is Not an Independent Risk Factor in a Cohort of Kidney Transplant Recipients and Living Donors.

Urinary dickkopf 3 (uDKK3) is a marker released by kidney tubular epithelial cells that is associated with the progression of chronic kidney disease (CKD) and may cause interstitial fibrosis and tubular atrophy. Recent evidence suggests that uDKK3 can also predict the loss of kidney function in CKD patients and kidney transplant recipients, regardless of their current renal function. We conducted a prospective study on 181 kidney transplant (KTx) recipients who underwent allograft biopsy to determine the cause, analyzing the relationship between uDKK3 levels in urine, histological findings, and future allograft function progression. Additionally, we studied 82 living kidney donors before unilateral nephrectomy (Nx), 1-3 days after surgery, and 1 year post-surgery to observe the effects of rapid kidney function loss. In living donors, the uDKK3/creatinine ratio significantly increased 5.3-fold 1-3 days after Nx. However, it decreased significantly to a median level of 620 pg/mg after one year, despite the absence of underlying primary kidney pathology. The estimated glomerular filtration rate (eGFR) decreased by an average of 29.3% to approximately 66.5 (±13.5) mL/min/1.73 m2 after one year, with no further decline in the subsequent years. uDKK3 levels increased in line with eGFR loss after Nx, followed by a decrease as the eGFR partially recovered within the following year. However, uDKK3 did not correlate with the eGFR at the single time points in living donors. In KTx recipients, the uDKK3/creatinine ratio was significantly elevated with a median of 1550 pg/mg compared to healthy individuals or donors after Nx. The mean eGFR in the recipient group was 35.5 mL/min/1.73 m2. The uDKK3/creatinine ratio was statistically associated with the eGFR at biopsy but was not independently associated with the eGFR one year after biopsy or allograft loss. In conclusion, uDKK3 correlates with recent and future kidney function and kidney allograft survival in the renal transplant cohort. Nevertheless, our findings indicate that the uDKK3/creatinine ratio has no prognostic influence on future renal outcome in living donors and kidney recipients beyond the eGFR, independent of the presence of acute renal graft pathology, as correlations are GFR-dependent.

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra.

Thrombotic microangiopathy (TMA) is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys. This review is specifically focused on post-transplant TMA (PT-TMA) involving kidney transplant recipients. Its reported prevalence in the latter population varies from 0.8% to 14% with adverse impacts on both graft and patient survival. It has many causes and associations, and the list of etiologic agents and associations is growing constantly. The pathogenesis is equally varied and a variety of patho genetic pathways lead to the development of microvascular injury as the final common pathway. PT-TMA is categorized in many ways in order to facilitate its management. Ironically, more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case. Pathologically, the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature. Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists. The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase. Management of the condition is also challenging and still largely empirical. It varies from simple maneuvers, such as plasmapheresis, drug withdrawal or modification, or dose reduction, to lifelong complement blockade, which is very expensive. A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective. This review aims to increase the awareness of relevant stakeholders regarding this important, potentially treatable but under-recognized cause of kidney allograft dysfunction.

Serum IL-6 predicts risk of kidney transplant failure independently of immunological risk.

Interleukin-6 (IL-6) is an important immune mediator and a target for novel antibody therapies. In this study, we aimed to determine whether serum IL-6 levels are associated with immunological risk, allograft rejection and outcomes in kidney transplant (Ktx) patients. We retrospectively analyzed the data of 104 patients who underwent Ktx at our center between 2011 and 2015. The patients were divided into high- and low-risk groups (n = 52 per group) based on panel reactive antibody (PRA) percentage ≥ 35%, the existence of pre-Ktx donor-specific antibodies (DSA), or a previous transplant. IL-6 concentrations were measured before and at 3 months, 12 months, and 3 years after Ktx. Serum IL-6 levels tended to be higher in high-risk patients than in low-risk patients prior to Ktx and at 12 months after Ktx; however, the difference did not reach statistical significance (pre-Ktx, high-risk: 1.995 ± 2.79 pg/ml vs. low-risk: 1.43 ± 1.76 pg/ml, p = 0.051; 12 mo. high-risk: 1.16 ± 1.87 pg/ml vs. low-risk: 0.78 ± 1.13 pg/ml, p = 0.067). IL-6 levels were correlated with the types (no rejection, T cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), or both) and time (<1 year vs. >1 year after Ktx) of rejection, as well as patient and graft survival. Patients with both TCMR and ABMR had significantly higher IL-6 levels at 3 months (14.1 ± 25.2 pg/ml) than patients with ABMR (3.4 ± 4.8 pg/ml, p = 0.017), with TCMR (1.7 ± 1.3 pg/ml, p < 0.001), and without rejection (1.7 ± 1.4 pg/ml, p < 0.001). Three years after Ktx, patients with AMBR had significantly higher IL-6 levels (5.30 ± 7.66 pg/ml) than patients with TCMR (1.81 ± 1.61 pg/ml, p = 0.009) and patients without rejection (1.19 ± 0.95 pg/ml; p = 0.001). Moreover, three years after Ktx IL-6 levels were significantly higher in patients with late rejections (3.5 ± 5.4 pg/ml) than those without rejections (1.2 ± 1.0 pg/ml) (p = 0.006). The risk of death-censored graft failure was significantly increased in patients with elevated IL-6 levels at 12 months (IL-6 level > 1.396 pg/ml, HR 4.61, p = 0.007) and 3 years (IL-6 level > 1.976 pg/ml, HR 6.75, p = 0.003), but elevated IL-6 levels were not associated with a higher risk of death. Overall, our study highlights IL-6 as a risk factor for allograft failure and confirms that IL-6 levels are higher in patients developing ABMR compared to TCMR alone or no rejection.

The Burden and Impact of Early Post-transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005-2021.

Background: Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods: We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score-weighted sensitivity, and subgroup analyses were performed. Results: Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%-1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31-0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21-8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92-55.5; subdistribution aHR, 7.15; 95% CI, 0.95-53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions: MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.

Genetic versus self-reported African ancestry of the recipient and neighborhood predictors of kidney transplantation outcomes in 2 multiethnic urban cohorts.

African American (AA) kidney recipients have a higher risk of allograft rejection and failure compared to non-AAs, but to what extent these outcomes are due to genetic versus environmental effects is currently unknown. Herein, we tested the effects of recipient self-reported race versus genetic proportion of African ancestry (pAFR), and neighborhood socioeconomic status (SES) on kidney allograft outcomes in multiethnic kidney transplant recipients from Columbia University (N = 1083) and the University of Pennsylvania (N = 738). All participants were genotyped with SNP arrays to estimate genetic admixture proportions. US census tract variables were used to analyze the effect of neighborhood factors. In both cohorts, self-reported recipient AA race and pAFR were individually associated with increased risk of rejection and failure after adjustment for known clinical risk factors and neighborhood SES factors. Joint analysis confirmed that self-reported recipient AA race and pAFR were both associated with a higher risk of allograft rejection (AA: HR 1.61 (1.31-1.96), P = 4.05E-06; pAFR: HR 1.90 (1.46-2.48), P = 2.40E-06) and allograft failure (AA: HR 1.52 (1.18-1.97), P = .001; pAFR: HR 1.70 (1.22-2.35), P = .002). Further research is needed to disentangle the role of genetics versus environmental, social, and structural factors contributing to poor transplantation outcomes in kidney recipients of African ancestry.

L-GrAFT7 has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China.

Background and Aims: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. Methods: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group. Results: L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group. Conclusions: The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.

INTRODUCTION: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). METHODS: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. RESULTS: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). CONCLUSION: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.

Donors With a Prior History of Cancer: Factors of Non-Utilization of Kidneys for Transplantation.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68-3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58-3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

18 years of face transplantation: Adverse outcomes and challenges.

BACKGROUND: Since the first procedure performed in 2005, face transplantation has been debated as viable approach for the treatment of severe craniofacial defects. Despite the benefits provided, the experience in face allotransplantation has brought to light a significant risk of complications, including allograft removal or loss, and mortality. The present study is intended to provide an updated review on complications and major challenges witnessed over 18 years of experience in the field. METHODS: A systematic review of PubMed, MEDLINE, Cochrane, Google, and Google Scholar databases on face transplantation was conducted according to PRISMA guidelines up to April 2023. Articles providing details on cases of face allograft loss, removal, and patient death were included. Online articles and media reports were assessed to include information not disclosed in peer-reviewed literature. Face transplant centers were contacted to have updated follow-up information on single-face transplant cases. RESULTS: The search yielded 1006 reports, of which 28 were included. On a total of 48 procedures performed in 46 patients, adverse outcomes were gleaned in 14 cases (29%), including seven allograft losses (14.6%), and the death of ten patients (21.7%). Chronic rejection was the leading cause of allograft loss, with a median time from transplant to irreversible rejection of 90 months (IQR 88.5-102). The main causes of death were infectious complications, followed by malignancies, non-compliance to immunosuppression, and suicide. The median time to death was 48.5 months (IQR 19-122). CONCLUSIONS: To the best of our knowledge, this is the first study providing a comprehensive review of adverse outcomes in face transplantation. Considering the high rate of major complications, the heterogeneity of cases and single-center approaches, and the absence of published standards of care, the development of a consensus by face transplant teams holds the key to the field's advancement.

Risk factors for infection in patients with a failed kidney allograft on immunosuppressive medications.

Patients with a failing kidney allograft are often continued on immunosuppression (IS) to preserve residual kidney function and prevent allosensitization. It has been previously accepted that maintaining patients on immunosuppressive therapy results in an increased risk of infection, hospitalization, and mortality. However, as the management of IS in patients with a failed kidney allograft continues to evolve, it is important to review the data regarding associations between infection and specific immunosuppression regimens. We present a review of the literature of failed kidney allograft management and infection risk, and discuss practices for infection prevention. Fifteen studies, published from 1995 to 2022, which investigated the experience of patients with failed allograft and infection, were identified. Infection was most commonly documented as a general event, but when specified, included infections caused by Candida, Mycobacterium tuberculosis, and Aspergillus. In addition, the definition of reduced "IS" varied from decreased doses of a triple drug regimen to monotherapy, whereas others did not specify which medications patients were receiving. Despite attempts at lowering net immunosuppression, patients with failed allografts remain at risk of acquiring opportunistic and non-opportunistic infections. Although opportunistic infections secondary to IS are expected, somewhat surprisingly, it appears that the greatest risk of infection may be related to complications of dialysis. Therefore, mitigating strategies, such as planning for an arteriovenous (AV) fistula over a hemodialysis catheter placement, may reduce infection risk. Additional studies are needed to provide more information regarding the types and timing of infection in the setting of a failed kidney allograft. In addition, more data are needed regarding specific medications, doses, and timing of taper of IS to guide future patient management and inform strategies for infection surveillance and prophylaxis.

BK polyomavirus DNAemia in pancreas transplant recipients compared to pancreas-kidney recipients.

BACKGROUND: BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients. METHODS: We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized. RESULTS: Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m2 . CONCLUSIONS: BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation.

BACKGROUND: Primary non-function (PNF) and early allograft failure (EAF) after liver transplantation (LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function (MEAF), PNF score by King's College (King-PNF) and Balance-and-Risk-Lactate (BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. METHODS: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic (ROC) and the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses. RESULTS: Of all 720 patients, 28 (3.9%) developed PNF and 67 (9.3%) developed EAF in 3 months. The overall early allograft dysfunction (EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0 (3.5-6.3), -2.1 (-2.6 to -1.2), and 5.0 (2.0-11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves (AUCs) of 0.871 and 0.891, superior to BAR-Lac (AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. CONCLUSIONS: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Validation of a prediction system for risk of kidney allograft failure in pediatric kidney transplant recipients: An international observational study.

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included. Allograft assessment included estimated glomerular filtration rate, urine protein-to-creatinine ratio, circulating antihuman leukocyte antigen donor-specific antibody, and kidney allograft histology. Individual predictions of allograft failure were calculated using the integrative box (iBox) system. Prediction performances were assessed using discrimination and calibration. The allograft evaluations were performed in 706 kidney transplant recipients at a median time of 9.1 (interquartile range, 3.3-19.2) months posttransplant; mean estimated glomerular filtration rate was 68.7 ± 28.1 mL/min/1.73 m2, and median urine protein-to-creatinine ratio was 0.1 (0.0-0.4) g/g, and 134 (19.0%) patients had antihuman leukocyte antigen donor-specific antibodies. The iBox exhibited accurate calibration and discrimination for predicting the outcomes up to 10 years after evaluation, with a C-index of 0.81 (95% confidence interval, 0.75-0.87). This study confirms the generalizability of the iBox to predict long-term kidney allograft failure in children, with performances similar to those reported in adults. These results support the use of the iBox to improve patient monitoring and facilitate clinical trials in children.

Conservative Kidney Management in Kidney Transplant Populations.

Conservative kidney management (CKM) has been increasingly accepted as a therapeutic option for seriously ill patients with advanced chronic kidney disease. CKM is active medical management of advanced chronic kidney disease without dialysis, with a focus on delaying the worsening of kidney disease and minimizing symptom burden. CKM may be considered a suitable option for kidney transplant recipients with poorly functioning and declining allografts, defined as patients with low estimated glomerular filtration rate (<20 mL/min per 1.73 m2) who are approaching allograft failure. CKM may be a fitting option for transplant patients facing high morbidity and mortality with or without dialysis resumption, and it should be offered as a choice for this patient population. In this review, we describe clinical considerations in caring for patients with poorly functioning and declining kidney allografts, especially the unique decision-making process around kidney replacement therapies. We discuss ways to incorporate CKM as an option for these patients. We also discuss financial and policy considerations in providing CKM for this population. Patients with poorly functioning and declining kidney allografts should be supported throughout transitions of care by an interprofessional and multidisciplinary team attuned to their unique challenges. Further research on when, who, and how to integrate CKM into existing care structures for patients with poorly functioning and declining kidney allografts is needed.

The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation.

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.

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year.

BACKGROUND: Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated. METHODS: We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression. RESULTS: A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64). CONCLUSIONS: This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.

Current Status and Perspectives on Recurrent IgA Nephropathy after Kidney Transplantation.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. IgAN progresses to end-stage kidney disease in 20-40% of patients within 20 years of diagnosis. Kidney transplantation is the most effective option for patients with end-stage kidney disease caused by IgAN, but recurrence can occur in the transplanted kidney. The IgAN recurrence rate varies from 1% to 10% per year and varies according to the follow-up period, diagnostic modality, and biopsy criteria. Of note, studies based on protocol biopsies have reported a higher incidence of recurrence, which also occurred earlier after transplantation. In addition, recent data show that recurrence of IgAN is a more significant cause of allograft failure than previously believed. Little is known about the pathophysiology of IgAN recurrence, but several potential biomarkers have been investigated. Among them, galactose-deficient IgA1 (Gd-IgA1), IgG anti-Gd-IgA1 antibodies, and soluble CD89 could play a pivotal role in disease activity. This review aims to describe the current status of recurrent IgAN, including the incidence, clinical characteristics, risk factors, and future perspectives, with a focus on the available therapeutic approaches.

Outcomes of Simultaneous Heart and Kidney Transplantation.

BACKGROUND: Simultaneous heart-kidney transplantation has been increasingly performed in end-stage heart failure patients with concurrent kidney dysfunction despite limited evidence supporting its indications and utility. OBJECTIVES: The purpose of this study was to investigate the effects and utility of simultaneously implanted kidney allografts with various degrees of kidney dysfunction during heart transplantation. METHODS: Using the United Network for Organ Sharing registry, long-term mortality was compared in recipients with kidney dysfunction who underwent heart-kidney transplantation (n = 1,124) vs isolated heart transplantation (n = 12,415) in the United States between 2005 and 2018. In heart-kidney recipients, contralateral kidney recipients were compared for allograft loss. Multivariable Cox regression was used for risk adjustment. RESULTS: Long-term mortality was lower among heart-kidney recipients than among heart-alone recipients when recipients were on dialysis (26.7% vs 38.6% at 5 years; HR: 0.72; 95% CI: 0.58-0.89) or had a glomerular filtration rate (GFR) of <30 mL/min/1.73 m2 (19.3% vs 32.4%; HR: 0.62; 95% CI: 0.46-0.82) and GFR of 30 to 45 mL/min/1.73 m2 (16.2% vs 24.3%; HR: 0.68; 95% CI: 0.48-0.97) but not in GFR of 45 to 60 mL/min/1.73 m2. Interaction analysis showed that the mortality benefit of heart-kidney transplantation continued up to GFR 40 mL/min/1.73 m2. The incidence of kidney allograft loss was higher among heart-kidney recipients than among contralateral kidney recipients (14.7% vs 4.5% at 1 year; HR: 1.7; 95% CI: 1.4-2.1). CONCLUSIONS: Heart-kidney transplantation relative to heart transplantation alone provided superior survival for dialysis-dependent recipients and non-dialysis-dependent recipients up to a GFR of approximately 40 mL/min/1.73 m2 but at the cost of almost twice the risk of kidney allograft loss than contralateral kidney allograft recipients.