Therapeutic apheresis in renal transplantation: An update.

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.

Antibody-mediated rejection after kidney transplantation in children; therapy challenges and future potential treatments.

Antibody-mediated rejection (AMR) remains one of the most critical problems in renal transplantation, with a significant impact on patient and graft survival. In the United States, no treatment has received FDA approval jet. Studies about treatments of AMR remain controversial, limited by the absence of a gold standard and the difficulty in creating large, multi-center studies. These limitations emerge even more in pediatric transplantation because of the limited number of pediatric studies and the occasional use of some therapies with unknown and poorly documented side effects. The lack of recommendations and the unsharp definition of different forms of AMR contribute to the challenging management of the therapy by pediatric nephrologists. In an attempt to help clinicians involved in the care of renal transplanted children affected by an AMR, we rely on the latest recommendations of the Transplantation Society (TTS) for the classification and treatment of AMR to describe treatments available today and potential new treatments with a particular focus on the pediatric population.

Immunogenic and immunotolerogenic effects of extracorporeal photopheresis in high immunological risk kidney recipients. A single center case series.

The immunomodulatory effects of extracorporeal photopheresis (ECP) have been used for the treatment of T-cell mediated disorders, such as rejection in organ transplantation. Currently, it is an established therapy for heart and lung rejection, but not for kidney transplantation (KT), where experience is limited. In addition, some data suggest that ECP could generate an immune response against infections, thus being an alternative for the treatment of rejection in case of active or high-risk of infection. In the present study, we analyze four cases of use of ECP as concomitant therapy in patients with KT and high risk of opportunistic infections due to the high burden of immunosuppression throughout their renal diseases. Two patients had concomitant viral infection (cytomegalovirus and BK virus, respectively) and three patients were on treatment for graft rejection. In the two patients with active viral infection, the infection was successfully controlled during ECP treatment. In all cases, ECP has been shown to be a safe procedure, without complications.

A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection.

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.

[Diagnosis and management of renal allograft rejection]. / Diagnostic et prise en charge thérapeutique du rejet en transplantation rénale.

Renal allograft rejection involves many mechanisms of innate and adaptive immunity, responsible for parenchymal inflammatory lesions that negatively impact the long-term outcomes of the renal allograft. The heterogeneous presentations of rejections in terms of clinical, biological and histological aspects make them difficult to manage in daily clinical practice. Indeed, current therapeutic strategies are disappointing in term of long-term outcomes, including graft survival. In this article, we will discuss the main effector mechanisms of rejection and their histological classification, as well as the existing treatments and those currently under evaluation.

: Le rejet du greffon rénal fait intervenir de nombreux mécanismes de l'immunité innée et adaptative, responsables de lésions inflammatoires parenchymateuses impactant négativement le devenir au long cours du greffon rénal. La grande hétérogénéité dans la présentation clinique, biologique et histologique des rejets de greffe en fait des entités difficiles à prendre en charge en pratique clinique quotidienne. En effet, les stratégies thérapeutiques actuelles montrent des résultats assez décevants pour le traitement des rejets, ce qui a comme conséquence une diminution significative de la survie des greffons. Nous aborderons dans cet article les principaux mécanismes effecteurs des rejets, leur classification histologique ainsi que les traitements existants et en cours de validation.

Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation.

Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection.

Improving Vaccine and Immunotherapy Design Using Biomaterials.

Polymers, lipids, scaffolds, microneedles, and other biomaterials are rapidly emerging as technologies to improve the efficacy of vaccines against infectious disease and immunotherapies for cancer, autoimmunity, and transplantation. New studies are also providing insight into the interactions between these materials and the immune system. This insight can be exploited for more efficient design of vaccines and immunotherapies. Here, we describe recent advances made possible through the unique features of biomaterials, as well as the important questions for further study.

Long Term Outcomes of Endovascular Therapy for Failing Distal Bypass Vein Grafts.

OBJECTIVE: Although distal bypass using vein has been established with acceptable outcomes for chronic limb threatening ischaemia (CLTI), the major issue affecting long term outcomes is vein graft disease. This study aimed to analyse the peri-procedural results and long term outcomes of endovascular therapy (EVT) for failing vein grafts after distal bypass. METHODS: A retrospective analysis of 113 failing vein grafts (94 patients, 113 limbs) after distal bypass between 2009 and 2019 at the study hospital. RESULTS: The mean age was 74 ± 9 years and 72% of the patients were men. Of the 113 grafts, 54 grafts (48%) were detected in asymptomatic patients, 41 grafts (36%) in patients with recurrent ulcer or gangrene, and 18 grafts (16%) in patients with rest pain. The failing grafts were treated by low pressure long inflation balloon angioplasty with a mean balloon size of 3.0 ± 0.8 mm. The mean procedural time was 60 ± 29 min and procedural success was 98% (111 grafts). During the mean follow up period of 34 months, EVT was performed a median frequency of two times (range 1-11 times). The primary and assisted primary patency of the EVT revised grafts were 41% and 80% at one year, 34% and 68% at three years, 31% and 58% at five years, respectively. Of 41 limbs with recurrent ulcer or gangrene, the wound healed in 34 limbs (85%). The complete healing rate was 71% at three months and 84% at 12 months. Eight patients required major amputation, and the freedom from major amputation rate was 96% at one year and 80% at five years. CONCLUSION: Long term outcomes including patency, wound healing rate, and amputation free survival after EVT for failing vein grafts were acceptable. EVT could be a viable alternative to surgical revascularisation in patients with a failing distal bypass graft for CLTI.

Successful treatment of acute kidney allograft rejection using extracorporeal photopheresis in the context of post-transplant lymphoproliferative diseases: three successive cases.

We reported 3 kidney transplant patients with PTLD who developed mixed AR following IS treatment minimization. AR episodes were treated with extracorporeal photopheresis (ECP), methylprednisolone and IVIG. In all patients, graft function improved under ECP and stabilized in the long term. These observations suggest that ECP is safe and efficient for treatment of AR in the context of PTLD.

Early surveillance biopsy utilization and management of pediatric renal allograft acute T cell-mediated rejection in Canadian centers: Observations from the PROBE multicenter cohort study.

BACKGROUND: Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly. METHODS: Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as >50% of patients having at least 1 surveillance biopsy in the first 9 months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring. RESULTS: A total of 261 biopsies were performed on 97 patients over 1-2 years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8 ± 1.2 vs 0.1 ± 0.4; P < .001] and a 3-fold higher rate from indication biopsies [0.3 ± 0.9 vs 0.1 ± 0.3; P = .04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);>i1t1 and < Banff 1A (86%); and ≥ Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n = 28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1). CONCLUSIONS: Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

Variation in immunosuppression practices among pediatric liver transplant centers-Society of Pediatric Liver Transplantation survey results.

BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.

TGF-ß1-Licensed Murine MSCs Show Superior Therapeutic Efficacy in Modulating Corneal Allograft Immune Rejection In Vivo.

Mesenchymal stromal cells (MSCs) are a promising therapeutic option for multiple immune diseases/disorders; however, efficacy of MSC treatments can vary significantly. We present a novel licensing strategy to improve the immunosuppressive capacity of MSCs. Licensing murine MSCs with transforming growth factor-ß1 (TGF-ß MSCs) significantly improved their ability to modulate both the phenotype and secretome of inflammatory bone marrow-derived macrophages and significantly increased the numbers of regulatory T lymphocytes following co-culture assays. These TGF-ß MSC-expanded regulatory T lymphocytes also expressed significantly higher levels of PD-L1 and CD73, indicating enhanced suppressive potential. Detailed analysis of T lymphocyte co-cultures revealed modulation of secreted factors, most notably elevated prostaglandin E2 (PGE2). Furthermore, TGF-ß MSCs could significantly prolong rejection-free survival (69.2% acceptance rate compared to 21.4% for unlicensed MSC-treated recipients) in a murine corneal allograft model. Mechanistic studies revealed that (1) therapeutic efficacy of TGF-ß MSCs is Smad2/3-dependent, (2) the enhanced immunosuppressive capacity of TGF-ß MSCs is contact-dependent, and (3) enhanced secretion of PGE2 (via prostaglandin EP4 [E-type prostanoid 4] receptor) by TGF-ß MSCs is the predominant mediator of Treg expansion and T cell activation and is associated with corneal allograft survival. Collectively, we provide compelling evidence for the use of TGF-ß1 licensing as an unconventional strategy for enhancing MSC immunosuppressive capacity.

Impact of HLA compatibility in recipients of kidneys from expanded criteria donors: A Collaborative Transplant Study Report.

Due to a widespread organ shortage, the use of expanded criteria donors (ECDs) in kidney transplantation has increased persistently, reaching approximately 40% in recent years. Whether human leucocyte antigen (HLA) matching between donor and recipient should be part of allocation algorithms in transplantation of ECD kidneys, and especially of ECD kidneys from ≥70-year-old donors, is still in question. To this end, 135,529 kidney transplantations performed between 2000 and 2017 and reported to the Collaborative Transplant Study were analysed and the impact of HLA-A+B+DR mismatches on death-censored graft and patient survival as well as on rejection episodes was investigated. Results were stratified according to donor status (standard criteria donor (SCD) versus ECD) and age of ECD. HLA incompatibility increased the five-year death-censored graft failure risk similarly strong in recipients of ECD and SCD transplants (hazard ratio (HR) per HLA mismatch 1.078 and 1.075, respectively; p < .001 for both). Its impact on rejection treatments during the first post-transplant year was also significant but slightly weaker for recipients of ECD transplants (risk ratio (RR) per HLA mismatch 1.10 for ECD transplants and 1.13 for SCD transplants; p < .001 for both). Mortality increased gradually from zero to six HLA mismatches in recipients of SCD transplants, whereas for ECD transplants a significant increase was notable only from zero to more than zero mismatches. A significant but slightly less pronounced impact of HLA incompatibility on graft failure was observed in transplants from ≥70- compared with <70-year-old ECDs (HR per mismatch 1.047 and 1.093; p = .009 and < 0.001, respectively). The influence of HLA mismatches on rejection treatments was the same for both ECD age groups (RR = 1.10, p < .001 and p = .004, respectively). Our data indicate that HLA matching should be part of allocation algorithms not only in transplantation of kidneys from SCDs but also from ECDs.

Treatment of antibody-mediated rejection with double-filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation.

Antibody-mediated rejection (ABMR) at early or late post-transplantation remains challenging. We performed a single-center single-arm study where four cases of acute ABMR and nine cases of chronic active ABMR (defined by Banff classification) were treated with double-filtration plasmapheresis (two cycles of three consecutive daily sessions with a 4-day gap between). At the end of the third and sixth DFPP sessions, the patients received rituximab 375 mg/m2 . After a median follow-up of 1078 (61-1676) days, kidney-allograft survival was 50%. Before DFPP/rituximab therapy, the median donor-specific alloantibody (DSA) mean fluorescence intensity (MFI) was 9160 (4000-15 400); 45 days (D45) later it had significantly decreased to 7375 (215-18 100) (P = .018). In addition, at one-year (Y1) post-therapy, MFI had decreased further, that is, 4060 (400-7850) (P = .001). In two patients, DSA MFIs decreased and remained below 2000. The slope of estimated glomerular-filtration rate within the 6 months preceding intervention was -1.18 mL/min/month and remained unchanged at -1.29 mL/min/month within the year after intervention. Proteinuria remained unchanged. Baseline Banff scores on repeat allograft biopsies (post-therapy D45, Y1) did not show any improvement. Side-effects were mild to moderate. We conclude that the combined DFPP/rituximab significantly decreased DSAs in ABMR kidney-transplant recipients but did not improve renal function or renal histology at 1-year follow-up.

Renal artery embolization of non-functioning graft: an effective treatment for graft intolerance syndrome.

BACKGROUND: Percutaneous renal artery embolization is a valid non-invasive technique alternative to nephrectomy for patients with symptomatic non-functioning allograft (graft intolerance syndrome-GIS). The purpose of this article is to report the experience of our centre. METHODS: We analysed retrospectively 15 patients with symptomatic non-functioning renal allograft treated with percutaneous embolization from 2003 to 2017. Occlusion was obtained with the injection of calibrated microspheres of increasing size (from 100 to 900 µm) and completed with 5 to 8 mm metal coils placement in the renal artery. RESULTS: Technical success was achieved in all cases at the end of the procedure. Clinical success was obtained in 11 patients (73%). In four cases, nephrectomy was necessary: in one case because of septic fever and in three cases because of GIS persistence. In one case, it was possible to perform another procedure to embolize a perirenal collateral from a lumbar artery. Four patients (27%) reported minor complications which spontaneously resolved during the hospital stay. CONCLUSIONS: According to the scientific literature, we believe that, in selected patients, percutaneous renal artery embolization is a valid treatment option for GIS thanks to its efficacy, repeatability, minimal invasiveness and the absence of severe complications.

Liver and kidney transplantation in polycystic liver and kidney disease. / Trasplante hepático y renal en la enfermedad poliquística hepatorrenal.

OBJECTIVE: To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease. MATERIALS AND METHODS: A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clínic de Barcelona [Clinical Hospital of Barcelona]. RESULTS: We included a total of 53 patients enrolled, 32 (60.3%) had indication for transplantation, of which 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis in one case and renal artery thrombosis in other were detected. In both groups there was one case of inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27-121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma). CONCLUSIONS: Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%).

Early Antibody-Mediated Kidney Transplant Rejection Associated With Anti-Vimentin Antibodies: A Case Report.

Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti-vimentin antibody. He was successfully treated with plasmapheresis, intravenous immunoglobulin, antithymocyte globulin, and methylprednisolone, with renal recovery. The follow-up biopsy specimen demonstrated decreased vimentin expression with decreased alloinflammation, and graft function remains stable at 1 year posttransplantation (estimated glomerular filtration rate, 62mL/min/1.73m2). We postulate that preformed anti-vimentin autoantibodies bound to vimentin expressed on apoptotic tubular epithelial cells induced by ischemia-reperfusion injury and to constitutively expressed vimentin on peritubular capillaries and podocytes. Our case is suggestive of the involvement of anti-vimentin antibody, for which the pathogenic epitopes may be exposed during ischemia-reperfusion injury.

First birth from a deceased donor uterus in the United States: from severe graft rejection to successful cesarean delivery.

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

Dialysis after graft loss: a Swiss experience.

BACKGROUND: Patients returning to dialysis after graft loss have high early morbidity and mortality. METHODS: We used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded. RESULTS: Seventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft. CONCLUSION: In summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation.

Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center.

BACKGROUND: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. METHODS: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. RESULTS: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. CONCLUSIONS: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.