Living Donor Kidney Recipients Research Articles

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Delayed graft function in pediatric living donor kidney transplantation.

Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p< .0001). Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.

Mycophenolate-Induced Hepatotoxicity Precipitates Tacrolimus Nephrotoxicity in a Kidney Transplant Recipient: A Case Report

Mycophenolate (mycophenolate mofetil [MMF]; mycophenolate sodium [MPS]) and tacrolimus (FK-506) are commonly and concomitantly used to prevent rejection in organ transplant. Mycophenolate-induced hepatotoxicity causing the reduced FK-506 metabolism with nephrotoxicity may be less appreciated, leading to inappropriate management. We describe a new living donor kidney recipient receiving pretransplant and post-transplant immunosuppressants including oral mycophenolate (MMF 1 g daily) and tacrolimus (FK-506 4-8 mg daily) who developed progressive liver dysfunction (up to 10-fold increase) despite the reduced FK-506 dosage (6 mg daily). A thorough investigation including infection, inflammation, and autoimmune hepatitis were unremarkable. With a withdrawal of MMF, his liver function improved, but persistently higher trough serum FK-506 level (12-15 ng/mL) and increased serum creatinine were notable. Moreover, the reintroduction of MPS with the reduced FK-506 dosage (4 mg daily) worsened liver function along with FK-506 nephrotoxicity (serum creatinine from 1.4-2.4 mg/dL). The replacement of MPS with mammalian target of rapamycin inhibitor not only resolved liver injury but also normalized serum FK-506 level and kidney function. Mycophenolate should be kept in mind as a cause of drug-induced hepatotoxicity that can reduce tacrolimus metabolism, leading to FK-506 nephrotoxicity and acute kidney injury in organ transplant.

342.9: Factors Associated With a Higher Need for Antihypertensive Medications at 12- Months Post Renal Transplantation

Background: Hypertension (HTN) after renal transplantation can be difficult to control and often requires multiple blood pressure (BP) medications. In this study we examined the incidence and risk factors of “difficult to treat HTN” at one year post kidney transplantation at our center. Method: A single center retrospective study of renal transplant recipients who underwent kidney transplantation between January 2017 and May 2020 with 12 months follow up. We reviewed patients’ demographics, results of pretransplant cardiovascular imaging, and the change of cardiovascular risk factors during the first-year post kidney transplantation. We divided patients according to the number of their blood pressure medications at one year into two groups; those who required none or one, and those who required two or more medications. We labeled those who required ≥2 as “difficult to treat hypertension”. The target BP during the time of this retrospective study was <140/90 mm Hg as per the published guidelines during the time of the study.1 Results: A total of 278 renal transplant recipients were included. The majority (74%) was ≥ 30 years, 58% were men and 80% were living-donor kidney recipients. Preemptive transplantation was 10.1%. PD and HD were 11.5% and 78.4%, respectively. At one year, 70.1% of the patients attained to the target BP goal. Of the total study population; (N: 105, 38%) required ≥ 2 BP medications (i.e., “difficult to treat HTN”). Factors related to a higher need for antihypertensive medications included age (50 vs. 39 years, P<0.001), prior history of hypertension (P=0.006), prior AV fistula vs. dialysis catheter (P=0.044) and diabetes mellitus (P<0.001). Dialysis vintage (including preemptive transplantation), type of dialysis (HD vs. PD), type of transplant (living donor kidney transplant vs deceased donor kidney transplant), and smoking were not different among the two groups. Patients with “difficult to treat HTN” at one year were more likely to have abnormal pre-transplant cardiovascular baseline imaging including abnormal ejection fraction <55% (P=0.044), abnormal wall motion on echocardiography (P=0.004), abnormal perfusion stress test (P<0.001), higher calcium scoring (P=0.002), abnormal cardiac catheterization (P<0.001), and a higher degree of calcifications on CT of pelvic arteries (P=0.006). Patients with “difficult to treat HTN” at one year were likely to have a higher BMI at 12 months (P=0.028) whereas rejection, change of creatinine, weight gain, persistent hyperparathyroidism or anemia at 12 months were not different among the two groups. Multivariate analysis of requiring ≥1 BP medication indicated a relation with age (aOR: 1.025, CI: 1.003-1.048, P=0.026); male vs. female (aOR: 2.413, CI 1.358-4.288, P=0.003); DM (aOR: 2.07, CI: 1.081-3.964, P=0.028); HTN (aOR 2.586, CI: 1.104-6.06, P=0.029). However, the odds ratio for BMI at 12 months was insignificant (aOR: 0.999, CI 0.948-1.053, P=0.98). Conclusion: At one year post transplantation, about two thirds of our renal transplant recipients required no or only one BP medication. Those who required more medications were more likely to be older, males, diabetic, or previously hypertensive. Recipients with abnormal baseline pre-transplant cardiovascular imaging were also more likely to require more medications. Reference:1. Taler SJ, Agarwal R, Bakris GL, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013;62.

P8.082: Incidence and Associated Factors With Uncontrolled Hypertension at 12- Months Post-renal Transplantation

Background: Uncontrolled hypertension (HTN) after renal transplantation is not uncommon. However, our center has not studied its incidence and risk factors post kidney transplantation before. Method: A single-center retrospective study of the renal transplant recipients who underwent kidney transplantation between January 2017 to May 2020 with12 months of follow-up. The goal target of hypertension treatment during this retrospective study was <140/90 mmHg as per the published guidelines at that time. We divided patients according to their blood pressure (BP) control at 12 months post kidney transplantation into two groups: controlled BP (≤140/90) and uncontrolled BP(> 140/90). We studied the association between the patients’ demographics and baseline cardiovascular risk factors and uncontrolled HTN 12 months post kidney transplantation. We also studied the association between pretransplant (baseline) cardiovascular imagings and uncontrolled HTN at 12 months. These tests included:(ejection fraction, wall motion abnormalities on echo, calcium scoring, perfusion stress test, cardiac angiogram, and the degree of calcifications on CT of pelvic arteries). Additionally, we studied the changes seen during the first 12 months post kidney transplantation. These included: creatinine change, rejection, weight change, A1C change, post-transplant diabetes, LDL change, PTH change from baseline, and persistent hyperthyroidism. Results: A total of 254 renal transplant recipients were included. 74% were ≥ 30 years, 58% were men, and 80% were living-donor kidney recipients. Preemptive transplantation was 10.1%, PD: 11.5% and HD: 78.4%. At one year, 76 (29.9%) of the patients did not attain the BP goal of 140/90. SBP decreased from baseline to 12 months by -7.2±18.6 mmHg in the group with controlled BP and whereas it increased by 3.5±16.9 mmHg in the group with uncontrolled BP. (P:<0.001). DBP decreased from baseline to 12 months by -4.1±12 mmHg in the group with controlled BP, whereas it increased by 2±13.7 mmHg in the group with uncontrolled BP (P<0.001). Among characteristics and baseline cardiovascular risk factors, factors associated with uncontrolled HTN included age (47 VS 41 years, P:0.008) and DM (P:0.012). Whereas gender, dialysis vintage, preemptive transplantation, type of dialysis (hemodialysis VS peritoneal dialysis), type of transplant (living donor kidney transplant VS deceased donor kidney transplant), and smoking were not different among the two groups. None of the pre-transplant (baseline) cardiovascular imaging findings were associated with having uncontrolled BP >140/90 at 12 months. Similarly, there was no association between uncontrolled HTN and creatinine change from baseline, rejection, weight change, A1C change, post-transplant diabetes, LDL change, PTH change from baseline, and persistent hyperthyroidism. However, higher BMI at 12 months was associated with a higher incidence of uncontrolled HTN (BMI 27.2±5.9 vs. 29.2±5.4, P: 0.013). Multivariate analysis showed that the predictors of uncontrolled blood pressure (>149/90 mmHg) included a higher creatinine (OR=1.016, CI=1.004-1.028. p=0.01) and smoking (OR=3.58, CI=1.001-12.8. p=0.05). Conclusion: At one-year post renal transplantation, about one-third (29.9%) of the renal transplant recipients had uncontrolled hypertension despite multiple BP medications. SBP and DBP significantly trended up from baseline after transplantation in those with uncontrolled hypertension. In contrast, SBP and DBP significantly decreased from baseline after transplantation in those with controlled hypertension. This interesting finding requires further confirmation by a controlled prospective study.

242.9: Do the Findings of Pre-transplant Cardiovascular Imaging Corollate With Having Persistent Hyperparathyroidism at Year Post Renal Transplantation?

Background: Hyperparathyroidism is common in chronic kidney disease, and it can persist post renal transplantation. It is unknown whether the findings of cardiovascular imaging pre- transplantation corollate with the persistence of hyperparathyroidism (persHPTH) at one-year post-renal transplantation. Method: A single center retrospective study of renal transplant candidates from January 2017 to May 2020. We collected patients’ demographics, cardiovascular risk factors, the findings of pre- transplant cardiovascular imaging (echo, nuclear cardiac perfusion stress test, calcium scoring, cardiac catheterization results and the degree of calcification/atherosclerosis of pelvic arteries on screening pelvic CT scan). We also collected iPTH values [at baseline (before transplant), 1- 6 months, 6-12 months, and 12-24 months post transplantation]. We defined persHPTH as iPTH ≥ 25.5 pmol/L after 12 months post kidney transplantation (normal= 12.73 pmol/L). Results: 287 renal transplant recipients were included. 74% were ≥ 30 years, 58% were men and 80% were living-donor kidney recipients. Preemptive transplantation was 10.1%, PD: 11.5% and HD: 78.4% (AVF: 42% versus Permcath: 58%). Dialysis ventage was 4.8±3.3 years for deceased donor kidney transplantation (DDKT) versus 2.4±2.6 years for living donor kidney transplantation (LKT). The prevalence of persHPTH was [n = 47 (16.4%)]. There were no association between persHPTH and the findings of pre- transplant cardiovascular imaging including echo findings (EF, LVH and abnormal wall motion), cardiac nuclear perfusion stress test (cardiac PET), cardiac catheterization, calcification/atherosclerosis of pelvic arteries seen on screening pelvic CT scan. However, the presence of calcium scoring ≥ 400 on pre -transplant cardiac PET scan was associated with higher incidence of persHPTH at 12 months post renal transplantation (37% versus 13.1%; P: 0.013). Conclusion: There was no association between the incidence of persHPTH post-renal transplant and pre-transplant cardiovascular imaging. However, higher calcium scoring PET scan (> 400) are associated with higher incidence of persHPTH at 12 months post renal transplantation.

Clinical significance of low pre-transplant donor specific antibodies (DSA) in living donor kidney recipients with negative complement-dependent cytotoxicity crossmatches (CDCXM), and negative flow cytometry crossmatches (FLXM) – A single-center experience

BackgroundIt is controversial whether all donor-specific antibodies (DSA) detected by the solid-phase single antigen bead (SAB) assay negatively affect kidney transplantation outcomes. The study aimed to evaluate the possible clinical significance of low pre-transplant DSA in living donor kidney recipients. We analyzed a group of patients with HLA-A, B, and -DR DSA reactivities below a virtual crossmatch (VXM) value of 5000 MFI but with all VXM DSA reactivities at HLA-DQ, -DP, and -Cw, which were not typed routinely for donors prior to transplantation. We also investigated the incidence of persistent and de novo DSAs in available posttransplant SAB assays. MethodsFrom the historical cohort of living donor recipients transplanted between 2014 and 2018 at our center (n = 82), 55 patients met the inclusion criteria, namely: these patients were > 18 years old with non-HLA identical sibling donors, who were not desensitized, who had available pre-transplant SAB results, and who had negative both complement-dependent cytotoxicity crossmatch (CDCXM) and flow cytometry crossmatch (FLXM) results. An additional donor HLA typing, performed for all 55 recipients, identified donor additional HLA-DQ, -DP, and -Cw DSA reactivities. These patients were then divided by SAB reactivity into three groups: 1) those with DSA-positive reactivities; 2) those with non-donor-specific anti-HLA reactivities (NDSA); and, 3) those who were anti-HLA-negative. All these recipients were followed for three years and checked for their de novo or persistent DSA. ResultsIn the studied cohort, DSA-positive, NDSA reactive, and anti-HLA negative recipients constituted 33%, 36%, and 31% of 55 patients, respectively. Non-routinely considered pre-transplant HLA-DQ, -DP, and -Cw DSA-positive reactivities were shown in as many as 78% of DSA-positive cases (group 1) with the lowest MFI value of 319 to DP4 and the highest MFI of 5767 to DQ2. Of the pre-transplant HLA-A, B, and -DR DSA reactivities, only -DR52 DSA reactivity reached the highest MFI value of 2191. These detected DSAs did not reduce the mean estimated glomerular filtration rate (eGFR) values and did not increase the incidence of proteinuria in recipients. While the 3-year graft survival was lower in the DSA-positive group (94.4%) with one recipient who lost kidney transplant, the difference was not significantly different (p = 0.7) from the NDSA (100%) and negative (100%) groups. In terms of the incidence of de novo acute antibody-mediated rejection (AMR) at three years after transplantation, no case has been reported in the cohort. This may suggest that low DSA-positive recipients do not experience higher rejection rate. However, DSA-positive recipients had a tendency for a higher frequency of C4d deposits in peritubular capillaries (PTC) and de novo DSA. ConclusionOur 3-year follow-up of patients with low pre-transplant DSA found no association with a deterioration in graft function and worse graft survival. Furthermore, we did not observe an increase in AMR in our patients with low DSA. A larger cohort and a longer follow-up period may be needed to evaluate the tendency of low DSA-positive recipients towards the higher incidence of C4d deposits in PTC and/or de novo DSA.

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.

Kidney Transplant Outcomes in elderly Recipients: An Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry Study

There is an increase in elderly patients receiving kidney transplant internationally. This study describes elderly kidney transplant recipient outcomes in Australia and New Zealand. The study included all adult first kidney transplant recipients in Australia and New Zealand from 2000 to 2015. Survival and graft outcomes were compared between elderly (≥70 years) and younger (18-69 years) recipients using Cox proportional hazards regression. Overall, 10651 kidney transplant recipients were included, of which 279 (2.6%) were elderly adults. The proportion of elderly recipients increased from 0.6 to 4.4% from 2000 to 2015. Compared with younger recipients, elderly recipients were more likely to receive kidneys from deceased donors, elderly donors, and expanded criteria donors. Elderly recipients experienced poorer patient survival with 1- and 5-year survival ranging from 96% to 97% and 79% to 81%, respectively, compared with 97% to 99% and 90% 95% in younger recipients, respectively. Elderly recipients experienced comparable rates of delayed graft function and, in living donor kidney recipients, lower rates of acute rejection. Kidney transplantation in the elderly population is increasing. Although elderly recipients had inferior survival and graft outcomes, elderly recipients generally received poorer quality kidneys. The outcomes achieved in this cohort of elderly adults are encouraging, and improving elderly recipient outcomes should be an important focus for research.

Primary pediatric live-donor-kidney transplant-recipients' outcomes by immunosuppression induction received in the United States.

We examined the association between induction type and outcomes of live-donor pediatric kidney recipients on tacrolimus and mycophenolate maintenance. We analyzed the SRTR standard analysis file to evaluate primary live-donor pediatric kidney recipients between 2000 and 2018. Recipients were grouped by induction type into three groups: alemtuzumab n=289, anti-thymocyte n=1197, and IL-2RA n=1625. Kaplan-Meier curves were generated for recipient and death-censored graft survival. Predictors of recipient and allograft survival were examined using Cox proportional hazards models. Models were adjusted for age, sex, ethnicity, renal failure etiology, HLA-mismatches, transplant year, steroid maintenance, preemptive transplantation, payor type, and donor factors such as age, sex, and donor-recipient relationship. The transplant center was included as a random effect to account for inter-center variability. Rejection rates at 6months (Alemtuzumab 9.5% vs. r-ATG 5.7% vs. IL2-RA 5.3%; P: .023) and 12months (Alemtuzumab 14.5% vs. r-ATG 10.8% vs. IL2-RA 9%; P: .028) were significantly higher in the alemtuzumab group. PTLD rate (Alemtuzumab 0.8% vs. r-ATG 2.2% vs. IL2-RA 1%; P: .028) was significantly higher in the anti-thymocyte group. In the multivariable models, induction type did not influence patient or death-censored graft survival within ten years post-transplant. In this large cohort of standard immunological risk primary pediatric live-donor kidney recipients, as compared to IL-2RA, neither alemtuzumab nor anti-thymocyte globulin was associated with improved long-term graft or recipient survival. In the first year post-transplant, recipients of alemtuzumab induction had a higher rejection rate, while PTLD was more frequently observed in the anti-thymocyte recipients.

LOW DOSE (4.5 MG/KG) OF THYMOGLOBULIN IS EFFECTIVE TO CONTROL T CELLS BUT NOT B CELLS AND CD56DIMCD57+, CD56DIMNKG2A+ NATURAL KILLER CELLS RESULTING IN DE NOVO DONOR-SPECIFIC ANTIBODY FORMATION AND ACUTE REJECTION IN NON-SENSITIZED LIVING DONOR KIDNEY RECIPIENTS WITH EARLY STEROID WITHDRAWAL

The optimal dose of Thymoglobulin as an induction regimen in Asian living donor kidney recipients has been rarely reported. Patients were randomly assigned to receive either 4.5 mg/kg (ATG4.5 group, n=19) or 6.0 mg/kg (ATG6.0 group, n=17) Thymoglobulin. All patients had corticosteroid withdrawal within 7 days. The primary end point was a composite of biopsy-proven acute rejection, de novo donor specific antibody, or graft failure. Until 49 months post-transplant, the rate of the composite end point was 47.4% in the ATG4.5 group whereas 17.6% in the ATG6.0 group. There was one case of death-censored graft failure in the ATG4.5 group whereas there was no mortality during the follow-up period (22 to 49 months). This study was ceased earlier than expected because we concerned about the more increasing risk of the composite end point in the ATG4.5 group. Compared to pre-transplantation, T (CD3+CD56-) cells, NK (CD3-CD56+) cells, and NKT (CD3+CD56+) cells were significantly decreased whereas B (CD19+) cells were not significantly affected by Thymoglobulin in the first week. Although T and NKT cells had recovered to the pre-transplant value in both groups, NK cells in the ATG6.0 were kept suppressed while NK cells in the ATG4.5 group had recovered to the pre-transplant value. Interestingly, CD56dimCD57+ cells were significantly increased whereas CD56dimNKG2A+ cells was significantly decreased in the ATG4.5 group compared with the ATG6.0 group until six months post-transplant. ATG 4.5 mg/kg induction and early corticosteroid withdrawal tended to increase the rate of de novo donor-specific antibody and biopsy-proven acute rejection. (ClinicalTrials.gov: NCT02447822)

Time-Varying Covariates and Risk Factors for Graft Loss in Kidney Transplantation

ObjectivesThe present study was designed to evaluate the factors involved in long-term graft survival in recipients of kidney transplantation. Materials and MethodsWe reviewed 755 Iranian adult recipients who underwent kidney transplantation at Shahid Labbafinejad Medical Center in Tehran, Iran. Patients were followed for 5 years after transplantation. The primary outcome was the time between transplantation and graft loss. Using Cox regression, we studied the effect of time-independent variables (recipients’ age and sex, donors’ age, and type of donor), time-dependent covariates (body mass index [BMI], systolic blood pressure, diastolic blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels, proteinuria and serum creatinine level), and immunosuppressive drugs on graft loss 60 months after transplantation. The results are presented as the hazard ratio (HR) with 95% confidence intervals. ResultsResult from Cox proportional hazards model showed that the HR of graft loss was 1.62 (95% CI: 1.03-2.54) in cadaveric donor compared with living donor kidney recipients. The HR of graft loss for recipient age was 1.02 (95% CI: 1.002-1.030). Moreover, according to obtained results, the risk of losing functional transplant increased for each mg/dL rise in serum creatinine at least 9% and at most 40%. Our results also showed that 1 unit increase of BMI has at least a 2% and at most a 15% decremented effect on the hazard ratio of graft loss. ConclusionsHaving lower levels of creatinine and receiving a kidney from a younger living donor were associated with a decreased risk of graft loss. Graft loss is more likely to occur in patients with lower BMI.

P1787DESENSITIZATION IN LIVE KIDNEY DONOR RECIPIENTS PROVIDES GOOD OUTCOME AT MID-TERM FOLLOW-UP

Abstract Background and Aims The recipients who have antibodies againts to donors’ HLA (Anti HLA- DSA) carrie a huge risk for allograf (AG) losing. In current study, it was retrospectively evaluated whether the live donor kidney recipients (LDKRs) under desensitization (DS) were exposed to more AG loss, lower AG survival and more complications. Method In 17 of 269 LDKRs had high anti-HLA DSA were found prior to kidney transplantation (KTX). DS was performed with plasmapheresis (PF) and rituximab (RTX) before KTX. In order to determine the risks of DS, LDKRs who had not PF for any reason, were admitted immediately before and after those with LDKRs under DS were used as controls (n: 31). Immucor™ luminex method was used for detecting the anti HLA DSA. DS was performed to the Rs who had more than 5000 MFI DSA against to at least one donor HLA locus with double check. Non-parametric Fisher’s exact test was used for statistical analysis because of distribution of our patients was heterogeneous. Results In 15 Rs had DSA more than 2 HLA loci (MFI range: 5880-21712), remaining 2 Rs had one HLA locus DSA (9959-7762). Mean PF number was of 7 before TX, while 3 after TX. RTX was used in 9 Rs (53%) before TX. KTX performed when anti DSA MFI below 2000 under triple immunosuppression plus anti-thymocitic globulin (ATG) induction therapy. In 4 Rs (13%) had DSA below 5000 MFI among controls (Cs). More female Rs (88% vs. 19%, p&amp;lt;001) were in Rs under DS. ATG was used in 65 % of Cs. Comparison of the complications between Rs under DS and Cs, rate of rejection (35% vs. 19%, respectively, p&amp;gt;0.05), rate of indication biopsy (24 % vs 16 %, p&amp;gt;0.05), rate of CNI toxicity (5.5% vs. 6.5%, p&amp;gt;0.05) were indifferent. During whole follow-up period, creatinine levels and eGFR were compatible at both groups. Urinary infections were more frequent in Rs under DS (53% vs 6.5%, p&amp;lt;0.001) while the rate of viral infections were same. Also, late AG rejection were found in only 2 Rs under DS. Loss of AG and mortality were not seen in Rs under DS. Allograft survival for 3 years were found same (100% vs 91.2%, respectively) in groups. Conclusion Although our results belong to a single center and also a small group, desensitization before kidney transplantation for high risk kidney recipients are seem to be useful, effective and successful procedure.

P1721PERI-OPERATIVE HYPERKALAEMIA IN DECEASED-DONOR KIDNEY TRANSPLANT RECIPIENTS

Abstract Background Hyperkalaemia is a common and life-threatening medical emergency present in up to 10% of acute hospital admissions. End-stage Kidney Disease (ESKD) patients undergoing transplantation are at increased risk of hyperkalaemia and although the prevalence of hyperkalaemia in ESKD is well described, few studies have assessed the incidence and treatment of hyperkalaemia in kidney transplant recipients. Here, we describe the results from a retrospective review of peri-operative hyperkalaemia in incident deceased-donor kidney transplant recipients. Methods We conducted a retrospective electronic health record review of 172 consecutive deceased-donor kidney recipients at Addenbrooke’s Hospital, Cambridge between November 2018 and November 2019. Patients receiving simultaneous pancreas/kidney transplants, simultaneous liver/kidney or multi-visceral transplants were excluded as were living-donor kidney recipients. Variables abstracted included demographics, the type of organ received, pre-transplant renal replacement modality, treatments received for hyperkalaemia, serum potassium values and admission and discharge dates. Data were summarised as frequency (%), mean ± standard deviation (SD) or median with interquartile range (IQR) as appropriate. Categorical variables were compared by Chi-squared test and continuous variables by Student's t-test or Mann–Whitney U-test based on their distribution. Results 172 patients received a deceased-donor kidney during the study period and the median age of all recipients was 56 (IQR 46-64.5) years. 110 (64%) patients received a DCD (donation after circulatory death) kidney with the remaining 62 (36%) receiving DBD (donation after brainstem death) kidneys. 110 (64%) of recipients received haemodialysis prior to transplant. Mean serum potassium prior to transplant was 4.22±0.61 mmol/L and immediately post-operatively was 4.69±0.61 mmol/L. 85 (49%) recipients required emergency treatment for hyperkalaemia post-operatively. The median serum potassium prior to treatment was 5.98mmol/L (IQR 5.7-6.2) with median time to treatment of 6.8 hours (IQR 2.4-9.6) after kidney reperfusion. Of these patients 64% underwent emergency haemodialysis as the first line treatment for hyperkalaemia, whilst 24 of the 31 patients treated with insulin/dextrose for hyperkalaemia went on to receive haemodialysis for hyperkalaemia. Median length of stay was longer in those receiving treatment for hyperkalaemia (9 days (7-13) vs 7 days (6-10), p=0.005). Additional data is described in the figure below. Conclusion Hyperkalaemia amongst kidney transplant recipients is common, particularly in the peri-operative period. Current management strategies contribute to morbidity, with haemodialysis in the first week also independently associated with increased healthcare costs per patient in the first year following transplantation. New oral potassium binders may offer an alternative or adjunct to current management but there is a lack of data for their use in transplant patients. Clinical trials in the transplant peri-operative setting are warranted.

Kidney transplantation: a safe step forward for regulatory immune cell therapy

On the basis of promising animal studies and following the translational path of immune cell therapy in oncology,1 the field of organ transplantation has begun preliminary investigations of infusing regulatory immune cells into graft recipients. These early trials aim to reduce patients' immunosuppressive drug burden and promote drug-free transplant tolerance. The ONE Study was established in 2011 as a multicentre collaborative effort (centres in France, Germany, Italy, the UK, and the USA) to compare the feasibility, safety, and efficacy of regulatory cell-based medicinal products (CBMPs) when combined with reduced immunosuppressive treatment in low-risk, living-donor kidney recipients.

Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation

BackgroundIn kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches. MethodsUsing the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model. ResultsA total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85–0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79–1.01, P = .05) with 2 HLA-DR mismatches. DiscussionOur study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft‐versus‐host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor‐specific tolerance results in improved outcomes remains unanswered. We collected follow‐up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper‐matched living‐donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 μmol/l (interquartile range [IQR] 72‐99) in the tolerant cohort and 118 μmol/l (IQR 99‐143) in the control group. Mixed linear‐model showed around 29% lower average creatinine levels throughout follow‐up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long‐term immunosuppression for many years, suggesting permanent donor‐specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

Collaboration Converts Cardiac Catastrophe During Living Donor Kidney Recipient Surgery to Long Term Success

Background Cardiovascular disease is more common in CKD and evaluation of perioperative risk for potential kidney transplant recipients is essential to reduce adverse postoperative complications. Collaborative work between multiple disciplines better prepares recipients for surgery and can mitigate adverse outcomes. A case presenting multidisciplinary teamwork to offset cardiac complications in setting of living donor (LD) recipient surgery is presented. Case 44 y/o man with diabetes mellitus type 1 and ESRD on hemodialysis for 1 year is evaluated for LD kidney transplant. He has history of myocardial infarct 5 years earlier s/p stent and stroke 5 years ago without sequelae. He has no symptoms of cardiovascular disease. Preoperative Echo shows EF 55% without pulmonary hypertension. Cardiolite nuclear medicine stress test reveals small fixed apical lateral defect suggestive of infarct without ischemia. Cardiac catheterization demonstrates left anterior descending (LAD) mid 80% stenosis, circumflex with 70-80% narrowing and right coronary artery (RCA) with proximal widely patent stent and distal 20-30% lesion. He had stents placed in LAD and circumflex (bare metal). He is cleared for LD transplant. He is taken to surgery 4 months later; undergoing successful anesthesia induction and the living donor kidney is anastomosed to recipient vein followed by sudden drop in BP, not responding to fluids. TEE shows EF 10%. The living donor kidney is detached from recipient vein, flushed and packaged per UNOS protocol. The team decides to notify the donor after anesthesia recovery and discuss option of offering the kdiney to the deceased donor list (subsequently donor concurred with this plan). Cardiology is consulted. Transplant Surgery closes wound. Recipient is emergently taken from operating room to heart cath lab (with Anesthesia in attendance) where an occluded LAD is found in addition to distal 90% circumflex and 75-80% RCA lesions. LAD occlusion is restented (bare metal stent) and IABP is placed. Patient is taken to intensive care unit where Critical Care Service provides support and stabilizes recipient. A huddle between Critical Care, Cardiology, Transplant Surgery, Anesthesia and Transplant Nephrology discussed options, relaying these to donor and recipient families. In the morning IABP is removed and recipient is cleared for transplant (repeat EF is 30%). Living donor kidney is successfully placed with slow but persistent fall in creatinine without need for dialysis on discharge. 10 years later, his Cr is 1.7mg/dl with measured iothalmate clearance of 58 ml/min and 490 mg proteinuria. Discussion Despite careful evaluation, unexpected postoperative complications may adversely affect kidney transplant surgery. Quick teamwork to address the problem mitigates risk. The framework of multidisciplinary care in this example of a cardiac complication during recipient surgery of a living donor kidney transplant enabled successful transplant and long term success.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy

Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.