Kidney transplantation in Icelandic patients, 2000-2019: are outcomes affected by low volume?

Background: In Iceland, a small number of kidney transplants from living donors (LDs) are performed at Landspitali University Hospital (LUH) in Reykjavik, while deceased donor transplants have until recently invariably been carried out abroad. In this study, we evaluated the outcome of kidney transplantation in Icelandic patients. Methods: This was a retrospective study that included all Icelandic residents who underwent kidney transplantation between 1 January 2000 and 31 December 2019. Data were obtained from the Icelandic End-Stage Kidney Disease Registry, medical records at LUH, and the Scandiatransplant database. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate from serum creatinine for recipients and donors aged >18 years, and the modified Schwartz equation for those aged ≤18 years. Survival was estimated using the Kaplan-Meier method, and the log-rank test was employed for group comparisons. Results: A total of 229 kidney transplants in 221 patients were performed during the 20-year period, of which 135 (58.9%) were from LDs. Transplants carried out at LUH were 118 (51.5%), of which 116 were from LDs. During a median follow-up of 7.4 years (range 0.1-20), 27 (12.2%) patients died, 20 (74%) of whom had a functioning graft. One-year patient survival was 99.1% [95% confidence interval (CI), 97.9-100], 5-year survival was 95.7% (95% CI, 92.7-98.7), and 10-year survival was 87.7% (95% CI, 82.4-93.4). Death-censored graft survival was 98.3% (95% CI, 96.6-100), 96.8% (95% CI, 94.4-99.2), and 89.2% (95% CI, 84.1-94.7) at 1, 5, and 10 years, respectively. Conclusions: Patient and graft survival are comparable with those of large transplant centers, demonstrating the feasibility of running a quality kidney transplant program in a small nation in collaboration with a larger center abroad.

Renal cell carcinoma in a transplanted kidney: a retrospective evaluation.

INTRODUCTION: Kidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48-82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10-30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature. OBJECTIVE: To determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development. MATERIALS AND METHODS: A retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm. RESULTS: The incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient. CONCLUSION: Laparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease.

Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases.

C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 "real-world" cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).

Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Long-term changes in cardiac remodelling in prevalent kidney graft recipients.

BACKGROUND: Approximately 15% of kidney transplant (KT) recipients develop de novo heart failure after KT. There are scarce data reporting the long-term changes in cardiac structure and function among KT recipients. Despite the improvement in renal function, transplant-related complications as well as immunosuppressive therapy could have an impact on cardiac remodelling during follow-up. We aimed to describe the long-term changes in echocardiographic parameters in prevalent KT recipients and identify the clinical and laboratory factors associated with these changes. METHODS: A centralised blinded review of two echocardiographic examinations after KT (on average after 17 and 39 months post-KT respectively) was performed among 80 patients (age 50.4 ± 16.2, diabetes 13.8% pre-KT), followed by linear regression to identify clinico-biological factors related to echocardiographic changes. RESULTS: Left atrial volume index (LAVI) increased significantly (34.2 ± 10.8 mL/m2vs. 37.6 ± 15.0 mL/m2, annualised delta 3.1 ± 11.4 mL/m2/year; p = 0.034) while left ventricular ejection fraction (LVEF) decreased (62.1 ± 9.0% vs. 59.7 ± 9.9%, annualised delta -2.7 ± 13.6%/year; p = 0.04). Male sex (ß = 8.112 ± 2.747; p < 0.01), pre-KT hypertension (ß = 9.725 ± 4.156; p < 0.05), graft from expanded criteria donor (ß = 3.791 ± 3.587; p < 0.05), and induction by anti-thymocyte globulin (ß = 7.920 ± 2.974; p = 0.01) were associated with an increase in LAVI during follow-up. Higher haemoglobin (>12.9 g/dL) at the time of the first echocardiography (ß = 6.029 ± 2.967; p < 0.05) and ACEi/ARB therapy (ß = 8.306 ± 3.161; p < 0.05) were associated with an increase in LVEF during follow-up. CONCLUSION: This study confirms the existence of long-term cardiac remodelling after KT despite dialysis cessation, characterised by an increase in LAVI and a decrease in LVEF. A better management of anaemia and using ACEi/ARB therapy may prevent such remodelling.

Evolution of HLA-sensitization according to immunosuppressive therapy management among kidney transplant patients returning to dialysis between 2008 and 2019: A French retrospective study.

BACKGROUND: The optimal management of immunosuppressive therapy (IT) after kidney allograft failure (KAF) remains controversial. Although maintaining IT may reduce HLA-sensitization and improve access to retransplantation, it may also increase the rate of immunosuppression-related complications. The overall impact on patient mortality is unknown. The main objective of this study was to compare the evolution of HLA-sensitization 6 months after KAF according to IT management. METHODS: Individual clinical and health care data were extracted from the French national end-stage kidney disease registry (Renal Epidemiology and Information Network [REIN]) and the French National Health Data system (SNDS), respectively. Patients aged > 18 years returning to dialysis after KAF between January 2008 and December 2019 in Lorraine were included. Patients were classified into two groups, IT continuation or IT discontinuation. HLA-sensitization was defined as an increase in incompatible graft rate (IGR) between KAF and 6 months post-KAF (change to a higher predefined category (0%-5%), (5%-20%), (20%-50%), (50%-85%), (85%-95%), (95%-98%), (98%-100%)). Secondary outcome was patient survival according to IT management. RESULTS: A total of 121 patients were included, 35 (29%) of whom continued IT. HLA-sensitization after KAF tended to be higher in the "IT discontinuation" group (57% vs. 38% in the "IT continuation" group, p = .07). In multivariate analysis, IT continuation was associated with a lower increase in IGR (OR .37, 95% CI [.14; .93]). IT management was not associated with patient mortality. CONCLUSIONS: Continuation of IT after KAF was associated with less change in IGR and was not associated with excess mortality.

Kidney retransplantation outcomes in adults aged 70 and older: Analysis of risk factors and survival.

BACKGROUND: An increasing number of older patients are undergoing kidney transplant. Because of a finite longevity, more patients will be faced with failing allografts. At present there is a limited understanding of the benefits and risks associated with kidney retransplantation in this challenging population. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network database of all adults ≥70 undergoing kidney retransplant from January 1, 2014 to December 31, 2022. We examined patient and graft survival of retransplanted patients compared to first time transplants. We also analyzed the risk factors that impacted the survival. RESULTS: During the study period there has been a significant rise in the number of retransplants performed, with 631 patients undergoing the procedure. Although clinically insignificant, overall graft, and patient survival rates were slightly lower in the retransplant group compared to the primary transplant group. With retransplant, patient survival was 91.3%, 75.6%, and 56.9% compared to 93.4%, 81.4%, and 64.4% with primary transplant at 1, 3, and 5 years, respectively. With retransplant, graft survival was 89.5%, 73.5%, 57.4% compared to 91.5%, 79.0%, and 63.6% in a primary transplant group at 1, 3, and 5 years, respectively. Multivariable analysis showed that factors predicting poor survival included longer time on dialysis before retransplantation and decreased functional capacity. No survival difference was noted between recipients of deceased versus living donor kidneys. Patients who underwent retransplantation before initiating dialysis had better patient and graft survival. CONCLUSION: Patients aged ≥70 achieve satisfactory outcomes following kidney retransplantation, highlighting that chronologic age should not preclude this medically complex population from this life-saving procedure. Improvement in functional status and timely retransplantation are the key factors to successful outcome.

Kidney donor age of 50 years or above is a risk factor for calcineurin inhibitor-induced nephrotoxicity.

INTRODUCTION: Calcineurin inhibitor (CNI)-induced nephrotoxicity (CNI-T) is a post-transplantation complication that leads to graft dysfunction. Older-donor kidney grafts may be susceptible to chronic CNI exposure because of long-term arteriolar damage. The primary aim of this study was to examine the CNI-T incidence and time-course changes in the graft function according to donor age. METHODS: We included 334 kidney transplant recipients. CNI-T was defined by Banff arteriolar hyaline thickening scores of ≥2 based on allograft protocol biopsy. Depending on donor age, participants were divided into the D > 70 (≥70 years), D60 (60-69 years), D50 (50-59 years), and D < 49: (≤49 years) groups. We investigated the extent to which CNI-T affected the transplanted kidney function. Patients who did not develop CNI-T during the study period were included in the non-CNI-T group; the remaining were grouped into the CNI-T group. RESULTS: The CNI-T incidence was higher in donors aged >50 years. Compared to D < 49, the CNI-T risk was 1.86 times higher in D50 and 2.9 times higher in D > 70. Furthermore, the CNI-T group exhibited a significantly lower graft function 10 years after transplantation. CONCLUSION: CNI-T incidence increases in donors aged ≥50 years and affects renal function after 10 years.

Influence of donor sex and age on graft outcome in kidney transplantation.

BACKGROUND: There is a known recipient sex-dependent association between donor sex and kidney transplant survival. We hypothesized that donor age also modifies the association between donor sex and graft survival. METHODS: First, deceased donor kidney transplant recipients (1988-2019, n = 461 364) recorded in the Scientific Registry of Transplant Recipients, the Australia and New Zealand Dialysis and Transplant Registry and the Collaborative Transplant Study were analyzed. We used multivariable Cox regression models to estimate the association between donor sex and death censored graft loss, accounting for the modifying effects of recipient sex and donor age; donor age was categorized as 5-19, 20-34, 35-49, 50-59 and ≥60 years. Results from cohort-specific Cox models were combined using individual patient data meta-analysis. RESULTS: Among female recipients of donors aged <60 years, graft loss hazards did not differ by donor sex; recipients of female donors ≥60 years showed significantly lower graft loss hazards than recipients of male donors of the same age [combined adjusted hazard ratio (aHR) 0.90, 95% CI 0.86-0.94]. Among male recipients, female donors aged <50 years were associated with significantly higher graft loss hazards than same-aged male donors (5-19 years: aHR 1.11, 95% CI 1.02-1.21; 20-34 years: aHR 1.08, 95% CI 1.02-1.15; 35-49 years: aHR 1.07, 95% CI 1.04-1.10). There were no significant differences in graft loss by donor sex among male recipients of donors aged ≥50 years. CONCLUSION: Donor age modifies the association between donor sex and graft survival. Older female donors were associated with similar or lower hazards of graft failure than older male donors in both male and female recipients, suggesting a better functional reserve of older female donor kidneys.

Sex-specific time trends of long-term graft survival after kidney transplantation - a registry-based study.

BACKGROUND: Sex-specific trends over time with respect to kidney graft survival have scarcely been described in earlier studies. The present study aimed to examine whether kidney graft survival differs between women and men over time. METHODS: This study was based on prospectively collected data extracted from a quality registry including all kidney transplant patients between January 1965 and September 2017 at the transplantation center of a university hospital in Sweden. The transplantation center serves a population of approximately 3.5 million inhabitants. Only the first graft for each patient was included in the study resulting in 4698 transplantations from unique patients (37% women, 63% men). Patients were followed-up until graft failure, death, or the end of the study. Death-censored graft survival analysis after kidney transplantation (KT) was performed using Kaplan-Meier analysis with log-rank test, and analysis adjusted for confounders was performed using multivariable Cox regression analysis. RESULTS: Median age at transplantation was 48 years (quartiles 36-57 years) and was similar for women and men. Graft survival was analyzed separately in four transplantation periods that represented various immunosuppressive regimes (1965-1985, 1986-1995, 1996-2005, and 2006-2017). Sex differences in graft survival varied over time (sex-by-period interaction, p = 0.026). During the three first periods, there were no significant sex differences in graft survival. However, during the last period, women had shorter graft survival (p = 0.022, hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.1-2.7, adjusted for covariates). Biopsy-proven rejections were more common in women. CONCLUSIONS: In this registry-based study, women had shorter graft survival than men during the last observation period (years 2006-2017).

Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model.

Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia-reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an 'on pump' therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.

Delayed Graft Function in Kidney Retransplantation: United Network for Organ Sharing Data With Linked Primary and Retransplant.

INTRODUCTION: There are several articles exploring the risk factors for primary delayed graft function (DGF). However, current literature does not include many resources on the risk factors for DGF when it is a recipient's second kidney transplant or look at short-term graft and patient survival of DGF retransplants. METHODS: United Network for Organ Sharing data from January 2008 to June 2021 were analyzed. Pancreas transplants, multi-organ transplants, and lost to follow-up transplants were excluded. Second transplant patients with DGF were identified. Multivariate logistic regression models based on the primary and second transplant characteristics were created. Survival analysis was performed with Kaplan-Meier methodology and assessed with log-rank test. RESULTS: A total of 2964 second kidney transplants were identified. Rate of DGF in the second transplant was 28.4% (843/2964) and 49.2% of them had a prior DGF in their first transplant (P < 0.001). Multivariate analysis confirmed that occurrence of DGF (odds ratio [OR] 1.5, P < 0.001) and graft loss due to acute rejection (OR 1.2, P < 0.005) in the primary transplant were predictors of reappearing DGF in the second transplant. Dialysis at transplant was the greatest risk factor from the second transplant (OR 3.539, P < 0.001). There was a decreased graft survival after 12 mo (77% versus 49% with log t-test <0.001) in the second transplant. However, DGF was not significantly associated with patient survival. CONCLUSIONS: This study shows the interaction between primary and second transplant in developing DGF. Survival analysis shows lower graft survival for retransplants in the case of DGF. This study opens the possibility of identifying additional risk factors for patients undergoing retransplant surgeries.

Novel transcriptomic signatures associated with premature kidney allograft failure.

BACKGROUND: The power to predict kidney allograft outcomes based on non-invasive assays is limited. Assessment of operational tolerance (OT) patients allows us to identify transcriptomic signatures of true non-responders for construction of predictive models. METHODS: In this observational retrospective study, RNA sequencing of peripheral blood was used in a derivation cohort to identify a protective set of transcripts by comparing 15 OT patients (40% females), from the TOMOGRAM Study (NCT05124444), 14 chronic active antibody-mediated rejection (CABMR) and 23 stable graft function patients ≥15 years (STA). The selected differentially expressed transcripts between OT and CABMR were used in a validation cohort (n = 396) to predict 3-year kidney allograft loss at 3 time-points using RT-qPCR. FINDINGS: Archetypal analysis and classifier performance of RNA sequencing data showed that OT is clearly distinguishable from CABMR, but similar to STA. Based on significant transcripts from the validation cohort in univariable analysis, 2 multivariable Cox models were created. A 3-transcript (ADGRG3, ATG2A, and GNLY) model from POD 7 predicted graft loss with C-statistics (C) 0.727 (95% CI, 0.638-0.820). Another 3-transcript (IGHM, CD5, GNLY) model from M3 predicted graft loss with C 0.786 (95% CI, 0.785-0.865). Combining 3-transcripts models with eGFR at POD 7 and M3 improved C-statistics to 0.860 (95% CI, 0.778-0.944) and 0.868 (95% CI, 0.790-0.944), respectively. INTERPRETATION: Identification of transcripts distinguishing OT from CABMR allowed us to construct models predicting premature graft loss. Identified transcripts reflect mechanisms of injury/repair and alloimmune response when assessed at day 7 or with a loss of protective phenotype when assessed at month 3. FUNDING: Supported by the Ministry of Health of the Czech Republic under grant NV19-06-00031.

Emerging Therapies for Antibody-Mediated Rejection in Kidney Transplantation.

Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing both active and chronic active AMR and highlight the ongoing clinical trials.

Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft.

Transmission of a malignancy from a donor's organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. However, treatment of patients with the disseminated cancers implies that after the graft removal and cessation of the immunosuppression, radiotherapy, chemotherapy, or immunotherapy with alpha-interferon (INF-α) or interleukin-2 (IL-2) are required. The case report presents a clinical case of a transmitted kidney graft with multiple metastases (MTS) in a 31-year-old woman with the spontaneous regression of the metastatic cancer after transplantectomy and cancellation of the immunosuppressive therapy. Obviously, the determining factor is the recognition of the tumor by the effectors of the antitumor immunity due to the human leukocyte antigen (HLA) mismatch between the donor and the recipient. Therefore, cancellation of the immunosuppressive therapy in cases of transferal of a malignancy with a transplanted organ allows the effectors of the immune system to distinguish the tumor as a foreign tissue and effectively eliminate this neoplasm.

Can We Predict Graft Intolerance Syndrome After Kidney Transplant Failure? External Validation of a Previously Developed Model.

Previously we established a prediction model for graft intolerance syndrome requiring graft nephrectomy in patients with late kidney graft failure. The aim of this study is to determine generalizability of this model in an independent cohort. The validation cohort included patients with late kidney graft failure between 2008 and 2018. Primary outcome is the prognostic performance of our model, expressed as the area under the receiver operating characteristic curve (ROC-AUC), in the validation cohort. In 63 of 580 patients (10.9%) a graft nephrectomy was performed because of graft intolerance. The original model, which included donor age, graft survival and number of acute rejections, performed poorly in the validation cohort (ROC-AUC 0.61). After retraining of the model using recipient age at graft failure instead of donor age, the model had an average ROC-AUC of 0.70 in the original cohort and of 0.69 in the validation cohort. Our original model did not accurately predict the graft intolerance syndrome in a validation cohort. However, a retrained model including recipient age at graft failure instead of donor age performed moderately well in both the development and validation cohort enabling identification of patients with the highest and lowest risk of graft intolerance syndrome.

A Universal Bleeding Risk Score in Native and Allograft Kidney Biopsies: A French Nationwide Cohort Study.

BACKGROUND: The risk of bleeding after percutaneous biopsy in kidney transplant recipients is usually low but may vary. A pre-procedure bleeding risk score in this population is lacking. METHODS: We assessed the major bleeding rate (transfusion, angiographic intervention, nephrectomy, hemorrhage/hematoma) at 8 days in 28,034 kidney transplant recipients with a kidney biopsy during the 2010-2019 period in France and compared them to 55,026 patients with a native kidney biopsy as controls. RESULTS: The rate of major bleeding was low (angiographic intervention: 0.2%, hemorrhage/hematoma: 0.4%, nephrectomy: 0.02%, blood transfusion: 4.0%). A new bleeding risk score was developed (anemia = 1, female gender = 1, heart failure = 1, acute kidney failure = 2 points). The rate of bleeding varied: 1.6%, 2.9%, 3.7%, 6.0%, 8.0%, and 9.2% for scores 0 to 5, respectively, in kidney transplant recipients. The ROC AUC was 0.649 (0.634-0.664) in kidney transplant recipients and 0.755 (0.746-0.763) in patients who had a native kidney biopsy (rate of bleeding: from 1.2% for score = 0 to 19.2% for score = 5). CONCLUSIONS: The risk of major bleeding is low in most patients but indeed variable. A new universal risk score can be helpful to guide the decision concerning kidney biopsy and the choice of inpatient vs. outpatient procedure both in native and allograft kidney recipients.

Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation.

BACKGROUND: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. METHODS: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. RESULTS: dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. CONCLUSIONS: Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.

H2S-Enriched Flush out Does Not Increase Donor Organ Quality in a Porcine Kidney Perfusion Model.

Kidney extraction time has a detrimental effect on post-transplantation outcome. This study aims to improve the flush-out and potentially decrease ischemic injury by the addition of hydrogen sulphide (H2S) to the flush medium. Porcine kidneys (n = 22) were extracted during organ recovery surgery. Pigs underwent brain death induction or a Sham operation, resulting in four groups: donation after brain death (DBD) control, DBD H2S, non-DBD control, and non-DBD H2S. Directly after the abdominal flush, kidneys were extracted and flushed with or without H2S and stored for 13 h via static cold storage (SCS) +/- H2S before reperfusion on normothermic machine perfusion. Pro-inflammatory cytokines IL-1b and IL-8 were significantly lower in H2S treated DBD kidneys during NMP (p = 0.03). The non-DBD kidneys show superiority in renal function (creatinine clearance and FENa) compared to the DBD control group (p = 0.03 and p = 0.004). No differences were seen in perfusion parameters, injury markers and histological appearance. We found an overall trend of better renal function in the non-DBD kidneys compared to the DBD kidneys. The addition of H2S during the flush out and SCS resulted in a reduction in pro-inflammatory cytokines without affecting renal function or injury markers.