Kidney Graft Research Articles

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier

BackgroundBK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier.Case presentationA 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of “decoy cells”. Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy.ConclusionsBKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

Known case of ESRD due to IgA nephropathy with myelodysplastic syndrome having perinephric hematoma and disseminated multi-drug resistant Klebsiella pneumonia infection in urinary tract, gastrointestinal tract and testes following living donor kidney transplantation: The strength of multidisciplinary team management

A 34 years old man, had increasing pain over grafted kidney with low urine output on post-operative ‘Day 7’ following living donor kidney transplantation. He was a known case of IgA nephropathy with end stage renal disease and Myelodysplastic Syndrome (MDS). CT abdomen revealed perinephric hematoma; cast effect on graft kidney; and the density over grafted kidney was decreased suggestive of rejection. He also had disseminated multi-drug resistant Klebsiella pneumonia infections in urinary tract, gastrointestinal tract and orchitis. Multi-disciplinary team’s management which includes nephrologists, general physicians, hematologists, uro-surgeons, vascular surgeons, radiologists, microbiologists and anesthetists saves patient’s life as well as transplant kidney.

Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

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).

Predictive Factors Associated with Delayed Graft Function Following Renal Transplantation: A Retrospective Cohort Study

Kidney transplantation has become a routine procedure for end-stage renal disease. Although improvement in short term graft patency has been achieved, delayed graft function (DGF) is one of the important complications following kidney transplantation. DGF results from ischemia-reperfusion injury and involves a multitude of contributing elements including donor characteristics and etiology of the end-stage renal disease. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are easily applicable methods for evaluation of systemic inflammation. We hypothesized that these parameters could refine the detection of the patients with DGF in post- renal transplantation and guide management. To test our hypothesis, we investigated whether the NLR, PLR, and creatinine reduction ratio CRR could serve as prognostic indicators for identifying patient cohorts at an elevated risk of negative treatment outcomes following renal transplantation. We also assessed demographic and clinical factors as an independent predictor to detect negative early graft function outcomes in patients after renal transplantation. This single center retrospective cohort trial comprising 55 patients who received a kidney graft from deceased or living donors was performed in Northern Cyprus Ministry of Health’s Dr. Burhan Nalbantoglu State Hospital, over a 6 year period. The demographic and clinical variables included age, gender, body mass index, the etiology of end-stage renal disease, kidney graft from living or deceased donors, NLR, PLR and CRR. DGF was defined as GFR<60 on the 21th day following renal transplantation. Of the patients included in this study, 26 (47.3%) and 29 (52.7%) received deceased and living donor kidney transplantation, respectively. On the 21st day following transplantation, 27 patients (49%) had an eGFR<60, whereas 28 patients (51%) had an GFR≥60. None of the patients had undergone dialysis within the first week after transplantation. There were no significant differences in demographic and clinical characteristics between the patients with eGFR 60 and eGFR 60. In logistic regression analysis, none of the predictors including etiology of the end-stage renal disease, source of donor, or demographic baseline characteristic were associated with DGF. We suggest that the NLR and PLR parameters are not associated with the presence of DGF after renal transplantation. Keywords: Renal transplantation, Delayed graft function, Renal failure, Glomerular filtration rate, End-stage renal disease.

IL-21-producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts.

Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cells marked by previous IL-21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNA-Seq revealed that these lymph node (LN) effector Tfh cells have transcriptional and clonal overlap with IL-21-producing kidney-infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21-producing effector Tfh cells in LNs and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21-producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining LN and locally within kidney grafts. Thus, IL-21-producing effector Tfh cells have multifaceted roles in Ab-mediated rejection after kidney transplantation by promoting B cell alloimmunity.

TMA in Kidney Transplantation.

Thrombotic microangiopathy (TMA) is a rare and devastating complication of kidney transplantation, which often leads to graft failure. Posttransplant TMA (PT-TMA) may occur either de novo or as a recurrence of the disease. De novo TMA can be triggered by immunosuppressant drugs, antibody-mediated rejection, viral infections, and ischemia/reperfusion injury in patients with no evidence of the disease before transplantation. Recurrent TMA may occur in the kidney grafts of patients with a history of atypical hemolytic uremic syndrome (aHUS) in the native kidneys. Studies have shown that some patients with aHUS carry genetic abnormalities that affect genes that code for complement regulators (CFH, MCP, CFI) and components (C3 and CFB), whereas in 10% of patients (mostly children), anti-FH autoantibodies have been reported. The incidence of aHUS recurrence is determined by the underlying genetic or acquired complement abnormality. Although treatment of the causative agents is usually the first line of treatment for de novo PT-TMA, this approach might be insufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve kidney function. Targeted complement inhibition is an effective treatment for recurrent TMA and may be effective in de novo PT-TMA as well, but it is necessary to establish which patients can benefit from different therapeutic options and when and how these can be applied.

The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States

New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N=2770) and post-AC (Feb-2020 to Dec-2021, N=2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P<0.001), and less percentage of MELD exception (4.6% vs 7.7%, P=0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P<0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P<0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P=0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P<0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.

Donor-derived myeloid sarcoma in a kidney transplant recipient: clinical case study and relevance of a multidisciplinary approach in therapy and diagnosis

Background. Malignant tumors are one of the main causes of unfavorable outcomes in solid organ transplant recipients in the long term after transplantation. Localization of these tumors in a transplanted organ may cause loss of graft function. After chronic graft dysfunction and infections, malignant neoplasms come next as one of the leading causes of late kidney graft loss. The incidence of different types of malignancies varies according to the transplanted organ. Knowledge of etiology, pathogenesis, peculiarities of diagnosis and treatment of malignant tumors in solid organ transplant recipients is a significant part of screening at any stage of post-transplant period. Late diagnosis of malignancies in a transplanted kidney amidst disconnected stages of treatment and follow-up leads not only to graft loss, but also jeopardizes the life of recipients.Clinical case description. The patient is a 29-year-old female. History: IgA nephropathy with nephrosclerosis. Renal replacement therapy (RRT) with long-term hemodialysis since March 2019. Kidney transplantation from a deceased donor to the right external iliac vessels on March 13, 2019. Graft function is immediate. In October 2020, a tumor in the transplanted kidney was detected for the first time. In November 2021, an emergency graft nephrectomy was performed for health reasons. Antibacterial, antifungal therapy was carried out. Results of morphological study of the removed renal graft with immunohistochemistry (IHC) were obtained. The structure and phenotype of the tumor are consistent with myeloid sarcoma. Trephine biopsy: normocellular bone marrow.Conclusion. The 29-year-old patient was diagnosed with donor-derived myeloid sarcoma in her kidney transplant with the development of paraneoplastic syndrome and multi-organ failure. Currently, the patient is receiving RRT by long-term scheduled hemodialysis. Organ recipients need to be managed by a multidisciplinary team of specialized and highly specialized specialists, taking into account comorbid status and features of the course of the underlying disease.

Repeated local ellipsoid protrusion supplements HLA surface characterization.

Allorecognition of donor HLA is a major risk factor for long-term kidney graft survival. Although several molecular matching algorithms have been proposed that compare physiochemical and structural features of the donors' and recipients' HLA proteins in order to predict their compatibility, the exact underlying mechanisms are still not fully understood. We hypothesized that the ElliPro approach of single ellipsoid fitting and protrusion ranking lacks sensitivity for the characteristic shape of HLA molecules and developed a prediction pipeline named Snowball that is fitting smaller ellipsoids iteratively to substructures. Aggregated protrusion ranks of locally fitted ellipsoids were calculated for 712 publicly available HLA structures and 78 predicted structures using AlphaFold 2. Amino-acid sequence and protrusion ranks were used to train deep neural network predictors to infer protrusion ranks for all known HLA sequences. Snowball protrusion ranks appear to be more sensitive than ElliPro scores in fine parts of the HLA such as the helix structures forming the HLA binding groove in particular when the ellipsoids are fitted to substructures considering atoms within a 15 Å radius. A cloud-based web service was implemented based on amino-acid matching considering both protein- and position-specific surface area and protrusion ranks extending the previously presented Snowflake prediction pipeline.

Tubulo-interstitial inflammation increases the risk of graft loss after the recurrence of IgA nephropathy.

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

Scandiatransplant Exchange Program (STEP): Development and Results From an International Kidney Exchange Program.

Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019. This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in ≥3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility.Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023. The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.

Multiple infusions of ex vivo-expanded regulatory T cells promote CD163+ myeloid cells and kidney allograft survival in non-lymphodepleted non-human primates

Clinical verification of adoptively transferred regulatory T cell (Treg) efficacy in transplantation remains challenging. Here, we examined the influence of autologous exvivo-expanded polyclonal Tregs on kidney graft survival in a clinically relevant non-human primate model. Peripheral blood Tregs were isolated and expanded using artificial antigen presenting cells. Immunosuppression was comprised of tapered tacrolimus and CTLA4 immunoglobulin, in five animals each without or with Treg infusions. Escalating Treg doses were administered 6, 10, 13, 16, 20, 23, 27 and 30 days after transplant. Infused Tregs were monitored for Treg signature, anti-apoptotic (Bcl-2) and proliferation (Ki67) marker expression. Treg infusions prolonged median graft survival time significantly from 35 to 70 days. Treg marker (Ki67 and Bcl-2) expression by infused Tregs diminished after their infusion but remained comparable to that of circulating native Tregs. No major changes in circulating donor-reactive T cell responses or total Treg percentages, or in graft-infiltrating T cell subsets were observed with Treg infusion. However, Treg infusion was associated with significant increases in CD163 expression by circulating HLA-DR+ myeloid cells and elevated levels of circulating soluble CD163. Further, graft-infiltrating CD163+ cells were increased with Treg infusion. Thus, multiple Treg infusions were associated with M2-like myeloid cell enhancement that may mediate immunomodulatory, anti-inflammatory and graft reparative effects.

48h Normothermic Machine Perfusion With Urine Recirculation for Discarded Human Kidney Grafts.

Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48h with all discarded kidneys. Median arterial flow ranged from 405 to 841mL/min. All kidneys excreted urine until the end of perfusion (median 0.43mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. Ex vivo normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.

Pharmarcomechanical thrombectomy combined with transluminal balloon angioplasty for treating transplant renal vein thrombosis

Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient’s renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma.

Case report on prolonged kidney graft survival without immunosuppressive therapy after allogeneic hematopoietic stem cell transplantation

Background. The possibility of inducing immunological tolerance in allogeneic organ transplant recipients is a research goal of the transplantology community, as it will ensure the likelihood of complete engraftment of a foreign organ. However, such a task presently remains difficult to accomplish.Objective: to demonstrate longterm kidney graft survival without signs of acute rejection and without immunosuppressive therapy in a patient who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a haploidentical donor for post-transplant lymphoproliferative disorder (PTLD).Methods and materials. Recipient’s graft function was assessed using clinical, laboratory, instrumental and pathomorphological examination methods. Results. With no immunosuppressive therapy for more than four years, the kidney recipient showed stable, satisfactory graft function.Conclusion. The described clinical case demonstrates the development of immunological tolerance to a kidney graft in a recipient of allogeneic hematopoietic stem cells (HSCs).

Design and testing of a humanized porcine donor for xenotransplantation

Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts.

Changes in vascular access profile for pediatric hemodialysis patients over time: A registry-based study from Catalonia.

The criteria for vascular access (VA) selection in pediatric hemodialysis (HD) population has changed over time until the current patient-centered approach using the individualized Life-Plan. We analyzed the type of VA used by incident and prevalent end-stage kidney disease (ESKD) pediatric patients (pts) treated with HD in Catalonia. Data from the Catalan Renal Registry of ESKD pts under 18 years of age undergoing kidney replacement therapy (KRT) were examined for a 22-year period (1997-2018). ESKD children starting KRT through HD decreased progressively from 55.6% (1997-2001) to 38.2% (2012-2018) and, conversely, there was an increase in pts starting KRT by preemptive kidney transplantation (KT) from 28.9% to 42.6% between the same periods (for both comparisons, p = 0.007). Most ESKD pts started HD by fistula (AVF) from 1997 to 2001 (56.5%) but this percentage decreased over time and no AVFs were used to start HD in children from 2012 to 2018. Likewise, the percentage of children starting HD by tunneled catheter increased progressively from 8.7% to 72.2% between the same periods (for both comparisons, p < 0.001). Regarding prevalent ESKD pts, children on HD decreased from 34.9% in 1997 to 4.7% in 2018 and, conversely, pts with a functioning kidney graft increased from 62.8% to 92.4% during the same periods (for both comparisons, p < 0.001). There was a progressive decrease in the percentage of children dialyzed by AVF from 100% in 1997 to 0% in 2018 (p < 0.001). The KT rate increased from 5.4 per million population (pmp) in 1997 to 17.1 pmp in 2018 (p = 0.007). The median time on HD prior to the first KT progressively decreased to 6.6 months (2014-2018). The high KT rate was a determining factor in choosing the VA type in the incident and prevalent pediatric population treated with HD in Catalonia.

Effect of Cardiac Arrest in Brain-dead Donors on Kidney Graft Function.

Cardiac arrest (CA) causes renal ischemia in one-third of brain-dead kidney donors before procurement. We hypothesized that the graft function depends on the time interval between CA and organ procurement. We conducted a retrospective population-based study on a prospectively curated database. We included 1469 kidney transplantations from donors with a history of resuscitated CA in 2015-2017 in France. CA was the cause of death (primary CA) or an intercurrent event (secondary CA). The main outcome was the percentage of delayed graft function, defined by the use of renal replacement therapy within the first week posttransplantation. Delayed graft function occurred in 31.7% of kidney transplantations and was associated with donor function, vasopressors, cardiovascular history, donor and recipient age, body mass index, cold ischemia time, and time to procurement after primary cardiac arrest. Short cold ischemia time, perfusion device use, and the absence of cardiovascular comorbidities were protected by multivariate analysis, whereas time <3 d from primary CA to procurement was associated with delayed graft function (odds ratio 1.38). This is the first description of time to procurement after a primary CA as a risk factor for delayed graft function. Delaying procurement after CA should be evaluated in interventional studies.