Kidney Graft Research Articles

SGLT2 inhibitors in diabetic and non-diabetic kidney transplant recipients: current knowledge and expectations.

The beneficial effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown recently in numerous randomized controlled trials (RCT) and systematic reviews. According to KDIGO guidelines, SGLT2i currently represent a first choice for diabetic patients with chronic kidney disease (CKD). In addition, a recent meta-analysis of 13 large led by the 'SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium' (SMART-C) provided solid evidence of SGLT2i beneficial effects in CKD or in patients with heart failure, with and without diabetes. Collectively, the patients treated with SGLT2i had a decreased risk of CKD progression, acute kidney injury (AKI), end-stage kidney disease (ESKD) or death from heart failure. Whether these cardio-renal benefits should be extrapolated to kidney transplant recipients (KTR) needs to be assessed in further studies. In this article, we report recent data accumulated so far in the literature, looking at the efficacy and safety of SGLT2i in diabetic and non-diabetic KTR. We found encouraging data regarding the use of SGLT2i in KTR with diabetes. These agents appeared to be safe, and they reduced body weight and blood pressure in this group of patients. Potential effects on kidney graft function and survival are yet to be investigated.

Enhancing Kidney Transplant Outcomes: The Impact of Living Donor Programs.

The protocol for deceased donor kidney transplants has been standardised. The procedure for a living donor has peculiarities derived from the differences in the graft. When a living kidney donor program is implemented, changes occur in both the profile of the kidney transplant candidate and in the postoperative treatments. To discover whether a living donor program influences the functional outcomes of kidney grafts in a longstanding classical deceased donor kidney transplant program and to identify the factors associated with transplant outcomes. Retrospective observational multicentre study. Kidney transplant patients in two urology referral centres for renal transplant in Spain between 1994 and 2019. Groups: TV (living transplant): patients given kidney transplants from living donors (n = 150); TCpre11 (deceased transplant previous to 2011): patients given kidney transplants from deceased donors before the living donor program was implemented (n = 650); and TCpost11 (deceased transplant after 2011): patients given kidney transplants from deceased donors after the living donor program was implemented (n = 500). Mean age was 55.75 years (18-80 years), higher in TCpre11. There were 493 female patients (37.92%) and 1007 male patients (62.08%). Mean body mass index (BMI) was 26.69 kg/m2 (17.50-42.78 kg/m2), higher in TCpre11. Mean ischemia time was 17.97 h (6-29 h), higher in TCpost11. Median duration of urethral catheter: 8 days (6-98 days), higher in TCpost11. Median duration of double-J ureteral stent: 58 days (24-180 days), higher in TCpost11. Pretransplant UTIs: 17.77%, higher in TCpre11 (25.69%) than in TV (12%), higher in TV (12%) than TCpost11 (9.2%), and higher in TCpre11 (25.69%) than TCpost11 (9.2%). Acute renal rejection in 9.33% of TV, 14.77% of TCpre11, and 9.8% of TCpost11. Multivariate analysis: TCpost11 featured higher BMI, more smoking, and chronic renal failure progression time. Lower use of nonantibiotic prophylaxis to prevent recurrent urinary tract infections, increased duration of urethral catheters due to obstructive problems, and favoured deterioration of kidney function was observed in the deceased donor program. The living donor (LD) program had a strong influence on deceased donor transplants in the prelysis phase. Implementation of a LD program was associated with a decrease in the likelihood of acute rejection in TCpost11 and an increase in the tendency towards normal kidney function. Implementing living donor transplant programs affects functional outcomes in deceased donor transplants, reducing the probability of acute rejection and increasing the tendency towards normal kidney function. Preventing recurrent urinary tract infections with measures other than antibiotics, smoking cessation, delaying the removal of the double-J stent from the graft, and pre-emptive transplant (transplant prior to dialysis) are associated with improved renal function of the graft.

Roles of Akirin1 in early prediction and treatment of graft kidney ischemia‒reperfusion injury.

Ferroptosis is a predominant contributor to graft kidney ischemia‒reperfusion injury (IRI), resulting in delayed graft function (DGF). However, much less is known about the early predicting biomarkers and therapeutic targets of DGF, especially aiming at ferroptosis. Here, we propose a precise predicting model for DGF, relying on the Akirin1 level in extracellular vesicles (EVs) derived from recipient urine 48h after kidney transplant. In addition, we decipher a new molecular mechanism whereby Akirin1 induces ferroptosis by strengthening TP53-mediated suppression of SLC7A11 during the graft kidney IRI process, that is, Akirin1 activates the EGR1/TP53 axis and inhibits MDM2-mediated TP53 ubiquitination, accordingly upregulating TP53 in two ways. Meanwhile, we present the first evidence that miR-136-5p enriched in EVs secreted by human umbilical cord mesenchymal stem cells (UM-EVs) confers robust protection against ferroptosis and graft kidney IRI by targeted inhibition of Akirin1 but knockout of miR-136-5p in UM sharply mitigates the protection of UM-EVs. The functional and mechanistic regulation of Akirin1 is further corroborated in an allograft kidney transplant model in wild-type and Akirin1-knockout mice. In summary, these findings suggest that Akirin1, which prominently induces ferroptosis, is a pivotal biomarker and target for early diagnosis and treatment of graft kidney IRI and DGF after kidney transplant.

Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Pediatric Transplant Experience from a Single Center in South India

Background and Objective: Pediatric renal transplantation is a life-saving procedure for children with end-stage renal disease. This study aims to analyze the outcomes of pediatric renal transplants at our center, focusing on patient demographics, donor sources, surgical techniques, posttransplant complications, graft survival, and rejection rates. Methodology: A retrospective analysis was conducted on 43 pediatric kidney transplant recipients. Data on recipient age, gender, donor type, pretransplant dialysis, donor characteristics, surgical techniques, native kidney disease, induction therapy, maintenance immunosuppression, posttransplant infections, graft survival, and rejection episodes were collected and analyzed. Results: We performed 43 pediatric kidney transplants in total. The average age was 13.7 years (±3.81), with 8 (18.6%) being under the age of ten, 11 (25.6%) being between the ages of eleven and fourteen, and 24 (55.8%) being between the ages of fifteen and eighteen. There were 43 recipients: 27 males and 16 females. There were four (9.3%) deceased donor renal transplants and 39 (90.7%) live-related kidney transplants. Right internal iliac artery and right external iliac vein anastomosis were found in 32 (74.4%) cases, right external iliac artery and right external iliac vein in 9 (20.9%), right common iliac artery and right common iliac vein in 1 (2.3%), and right common iliac and right internal iliac in 1 (2.3%). Induction was used in 27 recipients (62.8%). Graft survival was seen at 1 year in 42 (97.7%) patients and at 5 years in 34 (81%). Biopsy-proven rejection occurred in 22 (51.2%) of the recipients, with antibody-mediated rejection occurring in 8 (18.6%) and cellular rejection occurring in 22 (51.2%). Graft loss was caused by acute cellular rejection in three (23.1%) cases, graft pyelonephritis in 2 (15.4%), and an unknown cause in 2 (15.4%). There were no significant connections with antibody-mediated rejection. Conclusion: Our study provides valuable insights into the outcomes of pediatric renal transplantation at our center. Despite the challenges of graft rejection and posttransplant infections, favorable graft survival rates were achieved. Cellular rejection emerged as a significant risk factor for graft survival, highlighting the importance of effective immunosuppressive management. Our findings emphasize the need for close follow-up, infection control measures, and individualized immunosuppressive strategies to optimize long-term outcomes in pediatric renal transplant recipients. Further research is warranted to refine protocols and address the specific needs of this vulnerable patient population.

Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone.

Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates.61vs..89 and.90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

WCN24-2721 Donor-Specific Antibodies in Renal Transplantation and Their Impact on Kidney Graft Survival

WCN24-2721 Donor-Specific Antibodies in Renal Transplantation and Their Impact on Kidney Graft Survival

Pigs in Transplantation Research and Their Potential as Sources of Organs in Clinical Xenotransplantation.

The pig has long been used as a research animal and has now gained importance as a potential source of organs for clinical xenotransplantation. When an organ from a wild-type (i. e., genetically unmodified) pig is transplanted into an immunosuppressed nonhuman primate, a vigorous host immune response causes hyperacute rejection (within minutes or hours). This response has been largely overcome by 1) extensive gene editing of the organ-source pig and 2) the administration to the recipient of novel immunosuppressive therapy based on blockade of the CD40/CD154 T cell costimulation pathway. Gene editing has consisted of 1) deletion of expression of the 3 known carbohydrate xenoantigens against which humans have natural (preformed) antibodies and 2) the introduction of human 'protective' genes. The combination of gene editing and novel immunosuppressive therapy has extended life-supporting pig kidney graft survival to greater than 1 y and of pig heart survival to up to 9 mo. This review briefly describes the techniques of gene editing, the potential risks of transfer of porcine endogenous retroviruses with the organ, and the need for breeding and housing of donor pigs under biosecure conditions.

Investigating the Impact of AI on Shared Decision-Making in Post-Kidney Transplant Care (PRIMA-AI): Protocol for a Randomized Controlled Trial.

Patients after kidney transplantation eventually face the risk of graft loss with the concomitant need for dialysis or retransplantation. Choosing the right kidney replacement therapy after graft loss is an important preference-sensitive decision for kidney transplant recipients. However, the rate of conversations about treatment options after kidney graft loss has been shown to be as low as 13% in previous studies. It is unknown whether the implementation of artificial intelligence (AI)-based risk prediction models can increase the number of conversations about treatment options after graft loss and how this might influence the associated shared decision-making (SDM). This study aims to explore the impact of AI-based risk prediction for the risk of graft loss on the frequency of conversations about the treatment options after graft loss, as well as the associated SDM process. This is a 2-year, prospective, randomized, 2-armed, parallel-group, single-center trial in a German kidney transplant center. All patients will receive the same routine post-kidney transplant care that usually includes follow-up visits every 3 months at the kidney transplant center. For patients in the intervention arm, physicians will be assisted by a validated and previously published AI-based risk prediction system that estimates the risk for graft loss in the next year, starting from 3 months after randomization until 24 months after randomization. The study population will consist of 122 kidney transplant recipients >12 months after transplantation, who are at least 18 years of age, are able to communicate in German, and have an estimated glomerular filtration rate <30 mL/min/1.73 m2. Patients with multi-organ transplantation, or who are not able to communicate in German, as well as underage patients, cannot participate. For the primary end point, the proportion of patients who have had a conversation about their treatment options after graft loss is compared at 12 months after randomization. Additionally, 2 different assessment tools for SDM, the CollaboRATE mean score and the Control Preference Scale, are compared between the 2 groups at 12 months and 24 months after randomization. Furthermore, recordings of patient-physician conversations, as well as semistructured interviews with patients, support persons, and physicians, are performed to support the quantitative results. The enrollment for the study is ongoing. The first results are expected to be submitted for publication in 2025. This is the first study to examine the influence of AI-based risk prediction on physician-patient interaction in the context of kidney transplantation. We use a mixed methods approach by combining a randomized design with a simple quantitative end point (frequency of conversations), different quantitative measurements for SDM, and several qualitative research methods (eg, records of physician-patient conversations and semistructured interviews) to examine the implementation of AI-based risk prediction in the clinic. ClinicalTrials.gov NCT06056518; https://clinicaltrials.gov/study/NCT06056518. PRR1-10.2196/54857.

Comparing the prognostic performance of iBOX and biopsy-proven acute rejection for long-term kidney graft survival

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/− abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR’s prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.

Consequences of Nephrotic Proteinuria and Nephrotic Syndrome after Kidney Transplant.

Proteinuria is the main predictor of kidney graft loss. However, there is little information regarding the consequences of nephrotic proteinuria (NP) and nephrotic syndrome (NS) after a kidney transplant. We aimed to describe the clinical and histopathological characteristics of kidney recipients with nephrotic-range proteinuria and compare the graft surveillance between those who developed NS and those who did not. A total of 204 patients (18.6% of kidney transplants in the study period) developed NP, and 68.1% of them had NS. Of the 110 patients who underwent a graft biopsy, 47.3% exhibited ABMR, 21.8% the recurrence of glomerulonephritis, 9.1% IFTA, and 7.3% de novo glomerulonephritis. After a median follow-up of 97.5 months, 64.1% experienced graft loss. The graft survival after the onset of NP declined from 75.8% at 12 months to 38% at 5 years, without significant differences between those with and those without NS. Patients who developed NS fewer than 3 months after the onset of NP exhibited a significantly higher risk of death-censored graft loss (HR: 1.711, 95% CI: 1.147-2.553) than those without NS or those with late NS. In conclusion, NP and NS are frequent conditions after a kidney transplant, and they imply extremely poor graft outcomes. The time from the onset of NP to the development of NS is related to graft survival.

Deceased Kidney Donor Biomarkers: Relationship between Delayed Kidney Function and Graft Function Three Years after Transplantation.

With an increasing number of marginal donors, additional methods for the evaluation of cadaveric kidney quality are required. This study aimed to evaluate pretransplant deceased donor serum (s) and urine (u) biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18, and C-X-C motif chemokine 10 (CXCL10) for predicting early and late graft function. In total, 43 deceased kidney donors and 76 corresponding recipients were enrolled. Delayed graft function (DGF) occurred in 27.6% of cases. sIL-18, sKIM-1, uNGAL, and uKIM-1 were predictors of DGF. A model incorporating sIL-18, uKIM-1, and clinical factors was developed to predict DGF (AUROC 0.863). Univariate analysis showed a negative association between uKIM and graft eGFR at 6, 12, 24, and 36 months, but this was not confirmed in the multivariate analysis. In conclusion, we report a superior performance of donor biomarkers for predicting DGF and later graft function over serum creatinine. Higher levels of donor sIL-18 and uKIM in conjunction with expanded-criteria donors and longer cold ischemia times predicted DGF. With no renal tubular damage in zero-time donor biopsies, higher pretransplant urine and serum NGAL levels were associated with better allograft function one year after transplantation, and sNGAL with graft function three years after transplantation.

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

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. 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). 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). 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.

Gaining Deeper Insights Into Mechanisms of T Cell-mediated Acute Kidney Graft Injury.

Gaining Deeper Insights Into Mechanisms of T Cell-mediated Acute Kidney Graft Injury.

Specific features of anesthetic management in simultaneous pancreas and kidney transplantation in a recipient with morbid obesity

Introduction. Anesthetic management in simultaneous pancreas and kidney transplantation in recipients has some specific features. In addition to the presence of underlying pathology in the form of type 1 diabetes mellitus and secondary diabetic complications, pronounced comorbidities can often make some difficulties for an anesthesiologist.Aim. We have reported a clinical case showing the specific features of anesthetic support for simultaneous pancreas and kidney transplantation in a recipient with morbid obesity.Clinical Case Report. Specific features of the anesthetic management of a 42-year-old patient L. with morbid obesity (body mass index 43.3 kg/m2) and hypertension who underwent simultaneous pancreas and kidney transplantation have been described. A preoperative examination of this patient revealed predictors of difficult airways, so endoscopically assisted intubation was performed. The Trendelenburg position of the patient during surgical intervention due to an excess body weight led to the increased intrathoracic pressure intraoperatively. The pressure ventilation mode, the neutral position of the patient on the operating table, and the monitoring of ventilation efficiency made it possible to return the elevated intrathoracic pressure to normal. A preoperative examination by a cardiologist, timely diagnosis and treatment of hypertension at the stage of placing the patient on the waiting list made it possible to exclude adverse hemodynamic reactions at the main stages of the operation. The patient was extubated on surgery completion in the Operating Room. The pancreatic graft function and the kidney graft function were satisfactory.Conclusion. Our approaches ensured the safety and efficacy of anesthesiological support and contributed to the successful implementation of simultaneous pancreas and kidney transplantation in the recipient having the concomitant pathology in the form of morbid obesity.

Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study)

BackgroundChronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.DiscussionNo effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.Trial registrationClinicalTrials.gov NCT04561986. Registered on September 24, 2020

Adjuvant Chemotherapy in Patients with Locally Advanced Upper Tract Urothelial Carcinoma with or without Kidney Transplantation.

Background: The incidence of upper tract urothelial carcinoma (UTUC) is uniquely high in kidney transplant (KT) recipients in Taiwan. The evidence of adjuvant chemotherapy (AC) in UTUC is contradictory. We have sought to determine whether AC is associated with potential benefits related to locally advanced UTUC after KT. Methods: We retrospectively analyzed 134 patients with locally advanced UTUC (at least stage T2) and patients who were administrated AC after unilateral or bilateral nephroureterectomy with bladder cuff excision. Of these 134 patients, 57 patients fulfilled our inclusion criteria. We used 23 KT and 34 non-KT locally advanced UTUC patients for comparison. Results: The mean follow-up time was 52.35 ± 34.56 and 64.71 ± 42.29 months for the KT and non-KT groups, respectively. The five-year disease-free survival (DFS) and overall survival (OS) rates were 45.7% vs. 70.2% and 62.8% vs. 77.6%, for the KT and non-KT groups. The Kaplan-Meier curve and the log rank test revealed significant differences in the DFS and OS rates between the two groups, p = 0.015 and 0.036. The influence of chemotherapy on graft kidney function was mild. Only three in the KT group and two in the non-KT group developed > grade 2 nephrotoxicity. Conclusions: Our study suggested that KT patients with locally advanced UTUC who had been administered AC after surgery presented worse OS and DFS than non-KT patients. KT patients tolerated the AC course well, and their nephrotoxicity levels were mild and acceptable.

Abdominal normothermic regional perfusion in the United States: current state and future directions.

Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. Liver and kidney transplantation from thoracoabdominal NRP (TA-NRP) donors in the United States was found to have lower rates of delayed kidney graft function and similar graft and patient survival versus recipients of cardiac super rapid recovery (SRR) DCD donors. The excellent outcomes with NRP have prompted the expansion of NRP technology to abdominal transplant programs. Excellent early outcomes with liver and kidney transplantation have prompted the growth of NC-NRP procurement for abdominal-only DCD donors across the US, and now requires standardization of technical and nontechnical aspects of this procedure.

Taurine Deficiency Is a Hallmark of Injured Kidney Allografts.

Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival. We performed urine metabolomic profiling of kidney transplant recipients in the early and late phases after transplantation combined with transcriptomic analysis of human kidney allografts. Single-nucleus RNA sequencing data sets of mouse kidneys after ischemia-reperfusion injury were analyzed. We analyzed the association of urinary taurine levels and taurine metabolism genes with kidney function, histology, and graft survival. Urine taurine concentrations were significantly lower in kidney transplant recipients who experienced delayed graft function. In a mouse model of ischemia-reperfusion injury, the taurine biosynthesis gene, CSAD , but not the taurine transporter SLC6A6 , was repressed. In the late stage of transplantation, low level of taurine in urine was associated with impaired kidney function and chronic structural changes. Urine taurine level in the lowest tertile was predictive of graft loss. Expression of the taurine transporter SLC6A6 in the upper median, but not CSAD , was associated with chronic kidney injury and was predictive of graft loss. Low urine taurine level is a marker of injury in the kidney allograft, is associated with poor kidney function, is associated with chronic histological changes, and is predictive of graft survival. The differential expression of CSAD and SLC6A6 , depending on the time after transplantation and marks of injury, highlights different mechanisms affecting taurine metabolism.

Kidney Transplantation Outcomes of Patients With Chronic Hypotension in Dialysis

IntroductionPersistent chronic hypotension affects 5-10% of dialysis patients. It seems to be reversible after receiving a functioning graft, but data regarding its influence on transplant outcomes are scarce. We analyse the evolution of patients with chronic hypotension in dialysis who undergo kidney transplantation at our center. MethodsA retrospective observational study was conducted. Sixty-six patients with chronic hypotension (defined as systolic blood pressure ≤ 100 mmHg at the time of transplantation) were identified. A control group of 66 non-hypotensive patients was assigned and matched for organ source and age. The evolution of both groups was compared. ResultsHypotensive patients had higher rates of primary non-function (18.2% vs 6.1%, p= 0.03) mainly due to venous thrombosis of the allograft (15.2% vs 3%, p= 0.015), worse renal function at the end of follow-up (eGFR of 35mL/min/1.73m2 vs 48mL/min/1.73m2, p= 0.001) but there was no statistical difference in graft survival after censoring for primary non-function. After multivariable adjustment, chronic hypotension remained an independent predictor factor for kidney graft failure (adjusted HR of 2.85; 95% CI: 1.24-6.57; p= 0.014). Use of vasoactive drugs and anticoagulation in hypotensive patients was associated with 7.1% of venous graft thrombosis compared to 17.3% in those with no intervention (p= 0.68). Receiving a functioning graft implied blood pressure normalization in patients with chronic hypotension. ConclusionsChronic hypotension in dialysis has a negative impact on short-term kidney transplant outcomes but a lower impact on long-term results. It is reversible after receiving a functioning graft. Identifying this subgroup of patients seems crucial to implement measures aimed at improving transplant results.