Living Donor Kidney Transplant Recipients Research Articles

Pretransplant Dialysis and Preemptive Transplant in Living Donor Kidney Recipients.

The optimal timing of dialysis access placement in individuals with stage 5 CKD is challenging to estimate. Preemptive living donor kidney transplant (LDKT) is the gold-standard treatment for ESKD due to superior graft survival and mortality, but dialysis initiation is often required. Among LDKT recipients, we sought to determine which clinical characteristics were associated with preemptive transplant. Among non-preemptive LDKT recipients, we sought to determine what dialysis access was used, and their duration of use before receipt of living donor transplant. We retrospectively extracted data on 569 LDKT recipients, >18 years old, who were transplanted between January 2014 and July 2019 at UCSF, including dialysis access type (arteriovenous fistula [AVF], arteriovenous graft [AVG], peritoneal dialysis catheter [PD], and venous catheter), duration of dialysis, and clinical characteristics. Preemptive LDKT recipients constituted 30% of our cohort and were older, more likely to be White, more likely to have ESKD from polycystic kidney disease, and less likely to have ESKD from type 2 diabetes. Of the non-preemptive patients, 26% used AVF, 0.5% used AVG, 32% used peritoneal catheter, 11% used venous catheter, and 31% used more than one access type. Median (IQR) time on dialysis for AVF/AVG use was 1.86 (0.85-3.32) years; for PD catheters, 1.12 (0.55-1.92) years; for venous catheters, 0.66 (0.23-1.69) years; and for multimodal access, 2.15 (1.37-3.72) years. We characterized the dialysis access landscape in LDKT recipients. Venous catheter and PD were the most popular modality in the first quartile of dialysis, and patients using these modalities had shorter times on dialysis compared with those with an AVF. Venous catheter or PD can be considered a viable bridge therapy in patients with living donor availability given their shorter waitlist times. Earlier referral of patients with living donor prospects might further minimize dialysis need.

Transplant Renal Artery Stenosis in Living Donor Kidney Transplant Recipients: A Single Center Experience from Nepal

Introduction: Transplant renal artery stenosis (TRAS) is the most common preventable vascular complication in kidney transplantation with significant rates of graft loss and mortality. We aimed to study the demographics, prevalence, clinical presentation, and outcome of TRAS. Methods: We retrospectively reviewed medical records of all living donor kidney transplant recipients at Tribhuvan University Teaching Hospital from August 2008 to May 2021. Cases diagnosed with TRAS by ultrasound Doppler and/or renal CT angiogram were included. Data on demographics, clinical presentation, management, and outcomes were collected and analyzed. Among patients who underwent revascularization, pre and post-procedure creatinine, blood pressure (BP), and antihypertensive medicine burden were compared. Results: Among 620 living donor kidney transplantation, TRAS was present in 17 recipients (Male:Female = 16:1) (2.6%); mean age was 35.47±12.71 years. The median duration at diagnosis was one- month post-transplant (range: 5 days-9 months). The most common clinical features of TRAS were graft dysfunction and uncontrolled hypertension. Diagnosis of TRAS was confirmed with CT angiography in 13 patients. Ten patients underwent revascularization. Pre and post-revascularization mean serum creatinine was 356±210.49 μmol/L and 122.8±30.48 μmol/L (p=0.007) respectively, mean systolic BP was 200±12.47 mmHg and 133±13.38 mmHg (p=0.005) respectively and mean diastolic BP was 105±15.09 mmHg and 80±9.43 mmHg(p=0.005) respectively. Significant reduction in anti- hypertensive pill burden was achieved. Conclusion: Prevalence of TRAS was 2.6%. Most cases presented early with hypertension and graft dysfunction. Revascularization of significant stenosis had a favorable outcome in terms of BP control, antihypertensive pill burden, and preservation of renal function.

Changes in graft function after living donor kidney transplantation in children.

This study aimed to evaluate the change in graft function in two groups stratified by the estimated glomerular filtration rate (eGFR) at 1month after transplantation (eGFR-1M) in pediatric living donor kidney transplant recipients. Forty-three pediatric recipients were classified as those with an eGFR-1M ≥ 90mL/min/1.73 m2 (n = 19; high eGFR group) or those with an eGFR-1M of 60-89mL/min/1.73 m2 (n = 24; middle eGFR group). In the two groups, changes in the eGFR were retrospectively evaluated for 5years after kidney transplantation. The mean recipient age at transplantation in the high/middle eGFR group was 6.1 ± 3.4/7.8 ± 4.0years (P = 0.14). The mean eGFR-1, -12, and -60M (mL/min/1.73 m2) in the high/middle eGFR group were 106.8 ± 2.99/78.5 ± 1.52 (P < 0.001), 79.3 ± 3.22/62.7 ± 2.38 (P < 0.001), and 73.1 ± 4.16/59.2 ± 2.79 (P = 0.006), respectively. The change in the mean eGFR remained mostly parallel in the two groups. In both groups, the eGFR significantly decreased only between 1 and 12months after transplantation (P < 0.0001). Approximately 70% of the patients had an eGFR-60M ≥ 60mL/min/1.73 m2. The high and middle eGFR groups showed a rapid decline in the eGFR by 1year after transplantation, but the change thereafter was gradual. In pediatric living donor kidney transplant recipients, the eGFR was relatively well maintained up to 5years after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Creating a Single Inflow Orifice From Living Donor Kidney Allografts With Multiple Renal Arteries.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow. Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant. Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20–42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed–death-censored graft survival was 98.6%. Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients

IntroductionRegulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the...

Infection Risk in the First Year After ABO-incompatible Kidney Transplantation: A Nationwide Prospective Cohort Study.

ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised. In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection. We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461). The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.

Increased intrarenal post-glomerular blood flow is a key condition for the development of calcineurin inhibitor-induced renal tubular acidosis in kidney transplant recipients.

Hyperchloremic metabolic acidosis (HCMA) from renal tubular acidosis (RTA) is common in kidney transplant (KT) recipients. Calcineurin inhibitors (CNIs) are a potential cause of RTA, and whether HCMA is a determinant of poor graft prognosis is controversial. The subjects were living-donor KT recipients (LDKTRs, n=47) and matched donors (n=43). All cases of rejection, extrarenal causes, and respiratory disorders were excluded. HCMA was defined as having a [Na+]-[Cl- ] value of ≤34 or starting alkalization. We determined the potential causes of HCMA in LDKTRs at 3 months (m) and 1 year (y) post-KT. We examined renal hemodynamic parameters in 26 LDKTRs at 1 y post-KT: namely, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF; GFR/RPF) and pre-/post-glomerular vascular resistance (pre-/postVR). The HCMA incidence in the 3-m post-KT LDKTR group was higher than that of the donors (51.0%vs. 6.9%, p<0.001, adjusted odds ratio: 6.7-15.7). Among adjusted factors, the most dominant HCMA contributor was low hemoglobin concentration (Hb≤12g/dl). Compared to non-HCMA cases, HCMA patients had low FF and low post-VR (p=0.008, 0.003, respectively) suggesting increased intrarenal post-glomerular blood flow. The high pathological score of alternative arteriolar hyalinosis (aah) ≥2 was a significant HCMA risk. The tacrolimus trough level was not high in HCMA but was significantly high in HCMA in the low post-VR setting (p=0.002). Among LDKTRs, low hemoglobin level is an important contributor to the manifestation of HCMA in the induction period, and increased intrarenal post-glomerular blood flow is a key condition for the development of CNI-induced RTA.

POS-787 LONG-TERM OUTCOMES OF KIDNEY TRANSPLANTATION IN CHILDREN WITH CAKUT VERSUS NON-CAKUT CAUSES OF CHRONIC KIDNEY DISEASE

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of end stage renal disease in children. Little is known about long-term outcomes after kidney transplantation in this group. The aim of this study is to evaluate the clinical characteristics of pediatric kidney transplantation (KTx) in CAKUT children and its outcomes. We conducted a retrospective study, from December 2007 to December 2020, including living donor kidney transplant recipients ≤17 years transplanted in our center. Patients were divided into those with CAKUT and those with non-CAKUT as the cause of chronic kidney disease (CKD). Our aim was to compare delayed graft function (DGF) rate, acute rejection, complication’s rates, and graft loss between groups. A total of 259 living donor kidney transplants were done till 2019. 38 (15%) were ≤17 years, The cause of CKD was CAKUT in 13 patients (34,2%) and non-CAKUT in 25 patients. Of the latter, 15 (60%) had glomerular disease. The most common CAKUT-related cause of CKD was primary vesicoureteral reflux (84,6%). There was no difference in age between the groups, with a mean age of 13,4 +/- 2,9 years in the CAKUT group and 12,7 +/- 3,4 years in the non-CAKUT group (p=0,542). Recipients with CAKUT showed female preponderance, and were more likely to be seropositive for both CMV and EBV (all p<0,05). A nephrectomy is most often performed in patients with CAKUT (53,8%) versus 4,3% in the non CAKUT patients (p=0,001). For both groups, there was no difference in cytotoxic PRA (15,4 % vs 16%, p=0,331) or mean number of compatibilities (3,53 vs 2,92, p=0,314). The post transplant hypertension was significantly higher in non CAKUT recipients than in those with CAKUT (p=0,049). . Compared to non CAKUT-group, CAKUT patients had more urinary tract infection (p=0,043). There was no difference in DGF (7,7% vs 8%, p=0,734), Acute rejection (7,7% vs 20%, p=0,141) or graft loss (7,7% vs 8%, p=0,784). Graft survival of the transplant in children with CAKUT is favourable. However, they have an increased risk of urinary tract infections.

Death With a Functioning Graft Kidney: A Single-Center Experience of More Than 4 Decades.

Death with graft function is one of the most catastrophic events after kidney transplant. Various pre and posttransplant risk factors have been linked to death with graft function. Characterization of this event is crucial to set successful preventive measures. Here, we reported on death with graft function among living donor kidney transplant recipients seen at the Urology and Nephrology Centre at Mansoura University (Mansoura, Egypt) throughout a period of >4 decades. This single-center study included 2953 patients who received living donor kidney transplant between March 1976 and December 2018. Patient data were retrospectively analyzed. Patients who had death with graft function were compared with other patients with regard to pre- and posttransplant data. Causes of death with graft function were also studied. Among our patients (1654 male [56%] and 1299 female [44%] patients), death with graft function was reported in 9.9% of patients and responsible for 58.3% of deaths and 24.6% of graft losses. Male sex, pretransplant dialysis and blood transfusion, pre- and posttransplant diabetes and hypertension, high HLA mismatches, antithymocyte globulin induction, steroid and cyclosporine use, steroid dose, acute rejection episodes, and posttransplant infections and malignancy were significantly higher among the death with graft function group. However, multivariate analyses showed that only pretransplant diabetes, steroid dose, and posttransplant infections were risk factors for death with graft function. The most common causes of death with graft function were cardiovascular disease, infections, and malignancy. Death with graft function remains a significant hindrance to competent kidney transplant outcomes. We found that the most common contributors to this major event were cardiovascular disease, infections, and malignancy. More attention is needed to modify risk factors of cardiovascular disease, to update implementation policies for posttransplant vaccinations, and to conduct increased malignancy surveillance, as well to adopt less aggressive immunosuppression regimens.

Efficacy and Outcomes of CYP3A5 Genotype-Based Tacrolimus Dosing Compared to Conventional Body Weight-based Dosing in Living Donor Kidney Transplant Recipients.

Introduction:Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020).Methods:Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C0 on post-op day 4. Secondary end points included clinical outcomes and safety.Results:The proportion of subjects who achieved the target tacrolimus C0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up.Conclusion:Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity.

Effects of the Type of Intraoperative Fluid in Living Donor Kidney Transplantation: A Single-Center Retrospective Cohort Study.

PurposePerioperative fluid management in kidney transplant recipients is crucial to supporting the fluid, acid-base, and electrolyte balance required for graft perfusion. However, the choice of intraoperative crystalloids in kidney transplantation remains controversial. We conducted a single-center retrospective cohort study to evaluate the impact of intraoperative fluids on acid-base and electrolyte balance and graft outcomes.Materials and MethodsWe included 282 living donor kidney transplant recipients from January 2010 to December 2017. Patients were classified into two groups based on the type of intraoperative crystalloids used (157 patients in the half saline group and 125 patients in the balanced crystalloid solutions group, Plasma-lyte).ResultsCompared with the half saline group, the Plasma-lyte group showed less metabolic acidosis and hyponatremia during surgery. Hyperkalemia incidence was not significantly different between the two groups. Changes in postoperative graft function assessed by blood urea nitrogen and creatinine were significantly different between the two groups. Patients in the Plasma-lyte group exhibited consistently higher glomerular filtration rates than those in the half saline group at 1 month and 1 year after transplantation after adjusting for demographic differences.ConclusionIntraoperative Plasma-lyte can lead to more favorable results in terms of acid-base balance during kidney transplantation. Patients who received Plasma-lyte showed superior postoperative graft function at 1 month and 1 year after transplantation. Further studies are needed to evaluate the superiority of intraoperative Plasma-lyte over other types of crystalloids in relation to graft outcomes.

Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption.

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization.

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs).Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization.Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable.Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.

Establishment of Durable Chimerism with Minimal GvHD in Highly Mismatched Recipients Receiving an Investigational Facilitated Allo-HSCT

IntroductionWe previously reported the induction of kidney transplant tolerance by the establishment of durable whole blood and T-cell chimerism and withdrawal of immunosuppression (IS) in 26 of 37 highly mismatched recipients of combined stem cell and living donor kidney transplant recipients (KTx) with low risk of graft versus host disease (GvHD), using FCR001, an investigational cell therapy. The focus of the current analysis is to evaluate the impact of degree of bidirectional donor/recipient mismatching using high resolution allele typing at HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, on the ability to establish durable chimerism, allowing full immunosuppression (IS) withdrawal and the induction of transplant tolerance.MethodsIn this phase 2 trial, recipients received nonmyeloablative conditioning with fludarabine 30mg/m2 (Days -5, -4, -3), cyclophosphamide 50mg/kg (Days-3 and +3), 200 cGy TBI (Day-1) followed by KTx (Day 0). G-CSF mobilized peripheral blood mononuclear cells were apheresed from the donor >2 weeks prior to KTx, processed to remove GvHD-producing cells yet retain CD34 +cells and tolerogenic CD8+/TCR facilitating cells (FC) and cryopreserved until infusion day+1 after KTx. IS consisted of mycophenolate and tacrolimus. IS was weaned and discontinued in the presence of sustained donor T-cell chimerism (>50%), stable renal function and no evidence of biopsy-proven rejection.ResultsSamples from 32 of the 37 subject pairs were available for analysis; of these, three subjects did not have sufficient DNA to test for locus DPB1.All 32 recipients, ranging from age 18 - 65 years, have reached at least 4.5 years of follow-up up to 12 years. Two recipients were re-transplants. Of the 29 D/R pairs with data from all 12 alleles, 21 were mismatched between 6 to 12 alleles (6 related, 15 unrelated), 8 were mismatched between 2 and 5 alleles (all related). Of the three D/R pairs missing DP data, one was mismatched 6 of 10, another 10 of 10, and a third 2 of 10 alleles. Despite the high degree of mismatch, durable chimerism allowed for full IS withdrawal in 25 of these 32 subjects (time off IS from 3.5 - 11 years). 12/25 off IS were from unrelated D/R pairs and ≥ 8 HLA mismatches; the majority showed >95% donor whole blood/T cell chimerism. Three have exhibited stable mixed chimerism ranging between 40% - 60%. Of the subjects not off IS, two failed to engraft their cells; four lost chimerism by 4 months, and one developed GVHD. Durably chimeric patients retained chimerism after removal of IS, remain rejection-free without donor-specific antibody (DSA) with up to 12 years following KTx and have not resumed IS. Transiently chimeric subjects resumed endogenous hematopoiesis and are maintained on low dose IS with stable renal function. There have been two cases of GvHD: one grade 2 lower GI acute GvHD that developed during conversion from tacrolimus to sirolimus and responded to steroids; this patient has developed moderate chronic GvHD of the skin. He is off IS with normal renal function. The second presented late following development of severe gastrointestinal symptoms and manifested treatment-resistant lower GI GvHD with associated tissue-invasive CMV colitis that proved fatal at 11 months post-transplant.ConclusionsIn summary, high levels of durable chimerism and tolerance with a low (5.5%) incidence of GvHD has been achieved in highly mismatched related and unrelated recipients of FCR001 + kidney transplant. [Display omitted] DisclosuresKrieger: Talaris Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Tambur: Viela Bio and Sanofi: Consultancy; ThermoFisher: Speakers Bureau. Schneider: Talaris Therapeutics, Inc.: Current Employment. Olsen: Talaris Therapeutics, Inc.: Current Employment. Ildstad: Talaris Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

Unattended automated office blood pressure in living donor kidney transplant recipients

Purpose Hypertension is common in kidney transplant recipients (KTRs). For the evaluation of blood pressure (BP), 24-h ambulatory BP measurements (ABPM) are considered superior to usual office measurements but are also resource demanding and troublesome to many patients. We therefore evaluated the use of unattended automated office BP (AOBP) during the first year following living donor kidney transplantation and compared AOBP with ABPM as obtained 12 months after transplantation. Materials and methods Data were retrieved from a cohort of 57 KTRs (mean age 45 ± 14 years, 75% males) who all received kidneys from living donors and had a good graft function (estimated glomerular filtration rate (eGFR) 52 ± 16 ml/min/1.73 m2 at 12 months). Unattended AOBP was measured at each visit to the outpatient clinic using the BpTru® device, while ABPM was obtained by Spacelabs® equipment before and 12 months after transplantation. Results AOBP remained stable from month 2 (130.2 ± 10.8/82.2 ± 7.8 mmHg) to month 12 (129.0 ± 12.8/83.1 ± 9.6 mmHg) post-transplantation. At 12 months follow-up, ambulatory daytime systolic BP was slightly higher than AOBP (132.7 ± 10.7 vs. 129.4 ± 12.2 mmHg, p = 0.04), while diastolic BP was similar (82.7 ± 7.7 vs. 82.0 ± 10.2 mmHg). Using Bland–Altman plots, 95% limits of agreements were −17.9 to 24.5 mmHg for systolic and −16.5 to 15.1 mmHg for diastolic BP. When considering a target BP of ≤130/<80 mmHg, 62% had sustained hypertension, 9% white coat hypertension and 11% masked hypertension. Using multiple linear regression analysis, only urine albumin-creatinine ratio tended to predict a higher systolic AOBP (p = 0.07). Conclusion In a cohort of stable living donor KTRs, mean values of unattended AOBP using BpTru® are comparable to daytime ABPM with a misclassification rate of approximately 20%.

Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients.

Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes. Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-hproteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273. CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = -0.29, P=0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.

Evaluation of Community-Level Vulnerability and Racial Disparities in Living Donor Kidney Transplant

Living donor kidney transplant (LDKT) is the ideal treatment for end-stage kidney disease, but racial disparities in LDKT have increased over the last 2 decades. Recipient clinical and social factors do not account for LDKT racial inequities, although comprehensive measures of community-level vulnerability have not been assessed. To determine if racial disparities persist in LDKT independent of community-level vulnerability. This retrospective, multicenter, cross-sectional study included data from 19 287 adult kidney-only transplant recipients in the Scientific Registry of Transplant Recipients. The study included individuals who underwent transplant between January 1 and December 31, 2018. Recipient race and the 2018 US Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Census tract-level SVI data were linked to census tracts within each recipient zip code. The median SVI measure among the census tracts within a zip code was used to describe community-level vulnerability. Kidney transplant donor type (deceased vs living). Modified Poisson regression was used to evaluate the association between SVI and LDKT, and to estimate LDKT likelihood among races, independent of community-level vulnerability and recipient-level characteristics. Among 19 287 kidney transplant recipients, 6080 (32%) received LDKT. A total of 11 582 (60%) were male, and the median (interquartile range) age was 54 (43-63) years. There were 760 Black LDKT recipients (13%), 4865 White LDKT recipients (80%), and 455 LDKT recipients of other races (7%; American Indian, Asian, multiracial, and Pacific Islander). Recipients who lived in communities with higher SVI (ie, more vulnerable) had lower likelihood of LDKT compared with recipients who lived in communities with lower SVI (ie, less vulnerable) (adjusted relative risk [aRR], 0.97; 95% CI, 0.96-0.98; P < .001). Independent of community-level vulnerability, compared with White recipients, Black recipients had 37% lower likelihood (aRR, 0.63; 95% CI, 0.59-0.67; P < .001) and recipients of other races had 24% lower likelihood (aRR, 0.76; 95% CI, 0.70-0.82; P < .001) of LDKT. The interaction between SVI and race was significant among Black recipients, such that the disparity in LDKT between Black and White recipients increased with greater community-level vulnerability (ratio of aRRs, 0.67; 95% CI, 0.51-0.87; P = .003). Community-level vulnerability is associated with access to LDKT but only partially explains LDKT racial disparities. The adverse effects of living in more vulnerable communities were worse for Black recipients. The interaction of these constructs is worrisome and suggests evaluation of other health system factors that may contribute to LDKT racial disparities is needed.

Prevalence, risk factors and Impact of Post-transplant Tuberculosis on Live Donor Kidney Transplant Recipients: A Retrospective Study

Background: TB is encountered worldwide more frequently among renal transplant recipients than in the general population. It is reported to be nearly 50 times higher in the renal transplant population because of immunosuppression. TB may arise from unrecognized infection in the allograft or acquisition of new infection after transplantation. Objective: The aim of the current work was to determine prevalence and risk factors for development post-transplant TB, and the impact of post-transplant TB in live donor renal transplantation on both patient and graft survival. Patients and methods: This retrospective cohort study carried out in the Nephrology Unit, Mansoura Urology and Nephrology Centre in Association with Nephrology Unit, Zagazig University Hospitals in the period between January 2020 to December 2020. Included 210 patients out of 3200 kidney transplant recipients (KTRs) who underwent renal transplantation in the period between March 1976 and December 2019, divided into 2 main groups according to development of post-transplant tuberculosis, a group of 70 (KTRs) who developed tuberculosis after transplantation served as a study group and a matched group of 140 (KTRs) who did not develop tuberculosis after transplantation served as control group and evaluation of two groups through risk factor to develop TB, demographical data, clinical, laboratory and radiological evaluation. After that TB group was subdivided into 2 groups according to the site of infection: pulmonary and urinary TB. Results: Body mass index was higher among control group with statistically significant difference. Associated medical disorders as post-transplant diabetes, post-transplant bacterial and CMV infection had higher incidence among TB group. Liver enzymes and calcineurin (CNI) levels showed statistically significant difference among TB group before and during anti tuberculous treatment, in which liver enzymes were elevated while CNI levels were significantly reduced during antituberculous treatment. Post- transplant CMV infection was higher in patients who developed pulmonary TB. Graft and patient survival were comparable among both groups with no significant difference. Conclusions: It could be concluded that post-transplant diabetes, bacterial and CMV infections increase risk of development of post-transplant TB. There was no effect of post-transplant tuberculosis on both patient and graft survival.

Post-transplant allograft outcomes according to mismatch between donor kidney volume and body size of recipients with pre-transplant diabetes mellitus

AimsThe aim of this study was to investigate allograft outcomes when relatively small kidneys were donated to patients with pre-transplant diabetes mellitus (DM). MethodsFrom January 2010 to December 2018, 788 cases of non-sensitized living donor kidney transplant recipient and donor pairs were enrolled. The subjects were divided into four groups according to the relative size of kidney and pre-transplant DM status: non-DM large kidney, non-DM small kidney, DM large kidney, and DM small kidney. We compared allograft outcomes between these four groups. ResultsThe four groups did not show differences in the development of de novo donor-specific antibody and acute rejection. However, a significantly greater decline of allograft function and increased proteinuria were observed in the DM small kidney group. The highest death-censored graft loss rate (P = 0.008) was also observed in this group and the combination of relatively small kidney size and pre-transplant DM was an independent risk factor for death-censored graft loss. In addition, the relatively small kidney and pre-transplant DM showed significant interaction with each other. ConclusionsThe size mismatch between donated kidney volume and recipient body size should be considered in donor selection of patients with pre-transplant DM.

Erişkin canlı donör ve kadavra donör böbrek nakillerinde alıcıların intraoperatif hemodinamik parametrelerinin karşılaştırılması

Objective: There are many studies on kidney transplant anesthesia, there is not enough data in the literature in terms of intraoperative parameters according to the donor type. In this study, we aimed to compare the intraoperative hemodynamic parameters in adult patients who underwent living-donor and deceased-donor kidney transplantation (KT). Material and Methods: The patients who underwent KT were divided into 2 groups according to the donor kidney type. Recipients who underwent deceased donor transplantation were included in the study as Group 1. Among the living donor kidney transplant recipients, the same number of patients with similar demographic data as Group 1 were designated as Group 2. Both groups were compared in terms of recorded data and intraoperative hemodynamic parameters. Results: Twenty-four patients were included in the study. The mean durations of dialysis were 81.6 ± 64.8 and 16.8 ± 17.4 months for Group 1 and Group 2, respectively (p = 0.001). The mean cold ischemia time was significantly longer in Group 1 than Group 2 (p = 0.001). The mean operative urine output for Group 1 and Group 2 were 87.3 ± 149.6 and 634.2 ± 534.5, respectively (p = 0.002). Mean arterial pressure, heart rate, peripheral oxygen saturation and CVP values were all comparable between the two groups. Conclusion: Cold ischemia time is longer and operative urine volume is lower in deceased donor transplants compared to living donor transplants. With good preoperative preparation, close intraoperative follow-up, and proper fluid management, similar intraoperative hemodynamic parameters are achieved in both types of donor recipients. Keywords: Anesthesia, cadaver, hemodynamic monitoring, kidney transplantation, living donors