Living Donor Kidney Transplant Recipients Research Articles

Late Treatment With Autologous Expanded Regulatory T-cell Therapy After Alemtuzumab Induction Is Safe and Facilitates Immunosuppression Minimization in Living Donor Renal Transplantation.

The TWO Study (Transplantation Without Overimmunosuppression) aimed to investigate a novel approach to regulatory T-cell (Treg) therapy in renal transplant patients, using a delayed infusion protocol at 6 mo posttransplant to promote a Treg-skewed lymphocyte repopulation after alemtuzumab induction. We hypothesized that this would allow safe weaning of immunosuppression to tacrolimus alone. The COVID-19 pandemic led to the suspension of alemtuzumab use, and therefore, we report the unique cohort of 7 patients who underwent the original randomized controlled trial protocol. This study presents a unique insight into Treg therapy combined with alemtuzumab and is therefore an important proof of concept for studies in other diseases that are considering lymphodepletion. Living donor kidney transplant recipients were randomized to receive autologous polyclonal Treg at week 26 posttransplantation, coupled with weaning doses of tacrolimus, (Treg therapy arm) or standard immunosuppression alone (tacrolimus and mycophenolate mofetil). Primary outcomes were patient survival and rejection-free survival. Successful cell manufacturing and cryopreservation until the 6-mo infusion were achieved. Patient and transplant survival was 100%. Acute rejection-free survival was 100% in the Treg-treated group at 18 mo after transplantation. Although alemtuzumab caused a profound depletion of all lymphocytes, including Treg, after cell therapy infusion, there was a transient increase in peripheral Treg numbers. The study establishes that delayed autologous Treg therapy is both feasible and safe, even 12 mo after cell production. The findings present a new treatment protocol for Treg therapy, potentially expanding its applications to other indications.

#2207 CD3(+) T cell depletion does not predict short term outcomes in kidney transplant patients

Abstract Background and Aims Anti-thymocyte globulin (ATG) is the most frequently agent used for immunosuppression induction therapy after kidney transplantation. The efficacy of the ATG treatment is monitored by peripheral blood CD3(+) T cell counts. ATG dosing can be tailored to reach and keep the target commonly accepted as below 50/μL within the week of transplant. In this study, we investigated the significance of reaching CD3(+) T cell target regarding short term adverse outcomes of biopsy-proved rejection, BK viremia and infection related hospitalization in living donor kidney transplant recipients. Method This retrospective observational study was conducted on adult patients who received living donor kidney transplants from January 1, 2015 to October 1, 2022. Demographic, clinical and laboratory information were collected using electronical medical records. The average CD3(+) T cell counts of postoperative first 3 days were calculated. Patients with CD3(+) T cell counts ≤ 50/μL were classified as “Optimally Treated”, while the patients with CD3(+) T cell counts >50/μL were classified as “Suboptimally Treated”. The incidence of biopsy-proven rejection, BK viremia and infection related hospitalization in 6 months following the transplant surgery were compared in these two groups. Results Sixty one patients were included in the study. Twenty eight were women and the average age was 39 ± 12.7 years. Average HLA mismatch count was 3.6 ± 1.7. Ten patients were desensitized before kidney transplant. Average ATG dose was 6.8 ± 2.3 mg/kg. Mean average CD3(+) T cell count of postoperative first 3 days were 93.9 ± 87.8/μL. During 6 months of follow up, 34.4% (n = 21) had at least one biopsy proved rejection episode, 21.3% (n = 13) had at least one infection related hospitalization and 11.4% (n = 7) had BK viremia. According to average CD3(+) T cell counts of postoperative first 3 days, 16 patients were in “Optimally Treated” group, whereas 45 patients were in “Suboptimally Treated” group. The patients in both groups had similar mean age, gender distribution, HLA mismatch, pretransplant desensitization status and total ATG doses. In 6 months of follow-up, the patients in “Optimally Treated” and “Suboptimally Treated” groups had no statistically difference in incidence of biopsy-proved rejection, BK viremia and infection related hospitalization. Conclusion In our study, we could not find any evidence to confirm the significance of reaching CD3(+) T cell target of 50/μL in first 3 days after transplant surgery regarding short term adverse outcomes of biopsy-proved rejection, BK viremia and infection related hospitalization. The value of CD3(+) T cell monitoring to adjust ATG therapy after kidney transplant surgery is questionable. Thus, in the light of our findings, we do not support the use of CD3(+) T cell counts in optimization of induction therapy with ATG after renal transplantation.

#3045 Understanding BK polyomavirus: surveillance and clearance in kidney transplant recipients

Abstract Background and Aims BK virus allograft nephropathy (BKVN) can develop graft loss. The aim of this study was to describe BK viraemia and BKVN related factors, our experience in treatment and the impact in graft survival. Method We introduce a retrospective cohort of 78 kidney transplant recipients (KTRs) with BKV viraemia between January 2013 from January 2020 and with follow-up until December 31, 2022 in our center. Results Thirty-four (43%) were living donor KTRs, 30 (38.5%) DBD, 11 (14.1%) DCD III, and 2 (4.3%) DCD II. Twenty-seven (34.6%) of recipients were sensitized. Immunosuppressive induction was based on Anti-CD25 in 33 (42.3%), and antilymphocytes antibodies in 44 (56.4%). Basal treatment was TAC+MPA+PDN in 44 (56.4%) and TAC+iMTOR+PDN in 31 (39.7%). Median FK levels were 7.9 (ng/ml) in the first replication. Median BK load at first replication was 3636 [1030-97151]cp/ml. Median time to replication from transplant was 6 months, and from highest load 9 months. Immunosuppression adjustment after replication was switch to imTOR+FK 25 (32.1%), low FK 17 (21.8%), imTOR 4 (5.1%). Only surveillance was chosen in 27 (35.9%). Others therapies were Leflunomide 4 (5.1%), IVIG 6 (7.7%) or both 3 (3.8%). Photopheresis was used in 2 cases. Viraemia was cleared in 17/24 (70.8%) of the cases in which conversion to mTOR was performed as an immunosuppression adjustment strategy, versus 9 (56.3%) in which it was decided to lower FK and in 3 (75%) with low MMF. Ten cases in which surveillance was carried out became negative for viremia, possibly because they were patients with a lower replicative load. BKN occurred in 28/78 (36%) cases, interstitial fibrosis (ci>2) was found in 14/28 (48.27%). Graft rejection after BKN was developed in 11/28 (37.9%). Graft loss occurred in 26/78 (33.3%) of cohort and in 19 (65%)of patients with BKN, reaching a significant value. Viraemia clearance was reached in 41 (60.3%) in mean time of 10 months [4-27]. Mean time since BKVN until graft loss was 22.3 months [10.2-34.2]. Exitus occurred in 7/78 (9%) of replication cases and in 3/28 (10.7%)of BKN patients. Maximum BK load Exp β; [1-1], p 0.033, first replication load >10.000 (cp/ml) and deceased donor status (Exp β; 6,9 [2.43-19.57] and 2.98 [1.10-8.07] p 0.031, were related to BKVN in bivariate analysis. No significant differences were found between therapy in BKVN and graft loss, maybe due to low BKVN cases. Conclusion In our cohort, maximum BK load, first replication load >10,000 (cp/ml), and deceased donor status appear to be related to nephropathy. No significant differences were found between induction, basal or adjuvant therapy and graft loss. The current challenge is to stop replication before fibrosis, without increasing the risk of rejection.

Effects of Antithymocyte Globulin, Basiliximab, and Induction-Free Treatment in Living Donor Kidney Transplant Recipients on Tacrolimus-Based Immunosuppression.

Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment. We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections. We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group. In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.

An ethical analysis of conditional and partially directed live kidney donation among strangers—The Israeli experience

Living donor kidney transplantation (LDKT) is one of the most effective treatment options for people with end-stage renal disease. Traditionally, LDKT can be either “directed” or “nondirected,” based on whether the recipient is specified by the donor. Recently, there has been an increase in conditional and semidirected live kidney donation among strangers, where the donor specifies the characteristics of the recipient whom they wish to donate to. This practice has both gained popularity and sparked controversy in the state of Israel through the nonprofit organization Matnat Chaim. We analyze the ethical implications of this practice by applying traditional principles of medical ethics to conditional LDKT. Although semidirected and conditional LDKT presents some ethical challenges, overall, its practice effectively aligns with core ethical principles. The donors' right to make stipulations respects the donor’s autonomy, the practice avoids harm and benefits both donor and recipient, and justice and utility are upheld as the practice specifically benefits marginalized patients and optimizes resource utilization. Finally, we present data from our institution demonstrating how conditional LDKT increased transplantation for all ethnic groups; Jewish recipients of LDKT increased by 151.32% (P = .034) Arab recipients of LDKT increased by 111.11% (P = .036).

Nocardiosis in kidney transplant recipients: A tertiary care center experience

IntroductionKidney transplant recipients are at increased risk of opportunistic infections, including Nocardia. The incidence of nocardiosis in kidney transplant recipients is 0.4–1.3%. The data regarding its epidemiology and outcomes is limited. MethodsThis was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with Nocardia infection were included and followed. Results12 (1.1%) patients had a Nocardia infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. Nocardia infection occurred at a median of 26 months (range 4–235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (n = 5) cases had an episode of rejection in the preceding year of Nocardia diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced Nocardia recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (n = 4), and only one death was Nocardia-related. ConclusionNocardia may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for Nocardia prevention.

Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persistent Hyperparathyroidism: A Retrospective Study.

BACKGROUND Secondary hyperparathyroidism and coronary calcifications are common complications in chronic kidney disease. However, the relation between coronary calcium score (CCS) and persistent hyperparathyroidism (pHPT) after kidney transplantation (KT) remains unknown. MATERIAL AND METHODS This was a single-center retrospective study of KT candidates from January 2017 to May 2020. We collected patients' demographics, cardiovascular (CV) risk factors, and the findings of pre-KT CV imaging. We also collected parathyroid hormone (PTH) values before KT, at 1-6 months, 6-12 months, and 12-24 months after KT. We defined pHPT as PTH ≥25.5 pmol/L after 12 months post-KT. RESULTS A total of 111 KT recipients (KTRs) with a mean age of 50.4 years were included, of which 62.2% were men and 77.5% were living-donor KTRs. Dialysis modality used before KT was peritoneal dialysis in 9.9% and hemodialysis in 82.9%. Dialysis vintage was 3±2.9 years. The prevalence of pHPT was 24.3% (n=27), and the prevalence of severe coronary calcifications (CCS >400 Agatston units) was 19.8% (n=22). PTH values at baseline, 1-6 months, 6-12 months, and 12-24 months were not different among between CCS >400 or CCS <400 groups. However, pHPT after KT was significantly more prevalent in KTRs with severe CCS (37% vs 14.3%, p=0.014). Severe CCS was associated with less improvement of PTH values after KT (r=0.288, p=0.020). Otherwise, the findings of cardiac PET and coronary angiogram were not significantly different between pHPT and non-pHPT patients. CCS >400 was independently associated with pHPT after transplant (aOR=18.8, P=0.012). CONCLUSIONS Severe CCS on pre-KT cardiac assessment is associated with pHPT after KT.

Preoperative Intrathecal Morphine is Associated With Reduced Postoperative Pain, Agitation, and Delirium In Living Donor Kidney Transplantation Recipients

BackgroundPostoperative delirium after organ transplantation can lead to increased length of hospital stay and mortality. Since pain is an important risk factor for delirium, perioperative analgesia with intrathecal morphine (ITM) may mitigate postoperative delirium development. We evaluated if ITM reduces postoperative delirium incidence in living donor kidney transplant (LDKT) recipients. Methods296 patients who received LDKT between 2014 and 2018 at our hospital were retrospectively analyzed. Recipients who received preoperative ITM (ITM group) were compared to those who did not (control group). Primary outcome was postoperative delirium based on Confusion Assessment Method for Intensive Care Unit results during the first four postoperative days. ResultsDelirium occurred in 2.6% (4/154) and 7.0% (10/142) of ITM and control groups, respectively. Multivariable analysis showed age (OR: 1.07, 95% CI: 1.01-1.14; P = 0.031), recent smoking (OR: 7.87, 95% CI: 1.43-43.31; P = 0.018), preoperative psychotropics (OR: 23.01, 95% CI: 3.22-164.66; P = 0.002) were risk factors while ITM was a protective factor (OR: 0.23, 95% CI: 0.06-0.89; P = 0.033). ConclusionPreoperative ITM showed an independent association with reduced post-LDKT delirium. Further studies and development of regional analgesia for delirium prevention may enhance postoperative recovery of transplant recipients.

Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

Longevity Matching for Living Donor Renal Transplantation

This study identifies the effect of individual donor and recipient characteristics on graft survival in living-donor kidney transplantation (LDKT) using a recently described novel measure, kidney life years (KLYs). The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify first-time kidney-only LDKT recipients between 1987 and 2020 who did not experience death with a functioning graft (DWFG) and were not missing relevant information (n=87,290). Patient characteristics were evaluated using Cox and multiple regression analyses, with the dependent variable being KLYs. An equation for expected KLYs based on patient characteristics was created using regression coefficients. The equation was validated using bootstrapped Pearson correlations and then applied to the DWFG group for comparison. Based on statistical significance from Cox and multiple linear regression analyses, 9 of the original 18 variables were selected for inclusion in the equation. Variables with notable impact included HLA match points (0.021 KLYs; 95% CI: [0.019,0.024]; P ≤ .001), Donor Age (-0.030 KLYs; 95% CI: [-0.035,-0.025]; P ≤ .001), and Donor African American Ethnicity (-2.356 KLYs; 95% CI: [-2.552,-2.159]; P ≤ .001). Equation validation was supported, given a negative correlation (r=-0.071; P ≤ .001) between expected KLY change and observed graft failure. Expected KLY change was found to be greater in those who eventually DWFG when compared with all other LDKTs (t=-5.735, P ≤ .001). Increasing HLA match points may be more beneficial for graft longevity than minimizing donor age in comparisons using realistic between-donor differences. Additionally, greater average expected KLYs in those who ultimately DWFG may illustrate an opportunity for improved donor-recipient matching.

Acute Diarrhea in Early Post-Transplant Period in Living Donor Kidney Transplant Recipients

Background: Acute diarrhea is common in Myanmar. People are so used to diarrhea at least once a year that they do not think diarrhea as an important problem. Acute diarrhea in early post-operative period in renal transplant recipient may result in pre-renal failure and delay graft function. This study aimed to identify the prevalence of diarrhea, its severity and response to treatment in early post-operative period (3 weeks after transplant) in living donor kidney transplant (LDKT) recipients. Patients and Methods: LDKT recipients having acute diarrhea in early post-transplant period at two transplant centers (Mingaladon and Nay Pyi Taw) in Myanmar were analyzed over 10 years period; from 2013 to 2023 September. Acute diarrhea is defined as three or more semisolid or liquid stools per day for a minimum of 1 day duration. It was a hospital based observational study. After obtaining diet history and physical examination, laboratory tests were done. Clinical parameters (diet, fever, features of oral candidiasis, features of dehydration, examination of abdomen), stool examination (stool inspection, stool examination for ova and cyst, stool for Clostridium difficle toxin, stool culture), blood tests (total WBC count, serum creatinine, liver function tests) and blood trough level for Tacrolimus and mycophenolate mofetil were done. Management was given according to algorithm and their response to treatment was recorded. Dose modification of immunosuppressants were done depending on full blood count and blood level of them. Results: A total of 230 LDKT recipients were observed; among them, thirteen percent (30/230) of recipients developed acute diarrhea in early post-operative period. The age ranged from 14 to 73 years. A majority of them had mild form; mild dehydration without significant changes in hemodynamic status. The peak onset of diarrhea was 4 to 5 days after transplant; majority resolved over one week. They did not have oral candidiasis. Abdominal examination was normal except mild tenderness over grafted kidney in all of them. Total WBC count and platelet count were normal except in two cases. Stool examination did not show trophozoite or cyst. Stool for Clostridium difficile toxin was not identified. With dietary modification and oral rehydration solution, their motion was back to normal in sixteen percent (5/30). Folic acid therapy with or without probiotics made resolution of diarrhea in 33.3% (10/30). Anti-infective therapy was given in 10% (3/30) of cases; norfloxacin to 2 cases. Intravenous colistin to one case as he had enterocolitis and septicemia due to Klebsiella pneumonia. His stool culture as well as blood culture showed Carbepenem resistant Klebsiella pneumonia; he was known case of myelodysplastic syndrome. Blood level of mycophenolate mofetil was normal; however, the dose was reduced in 2 cases owing to leucopenia or thrombocytopenia. Blood tacrolimus trough level was normal in two-third (20/30); and, it was high in one-third of them (20/30). They passed formed stool 24 - 48 hours after dose reduction of tacrolimus. Conclusion: In this study, 13% of the LDKT recipients had acute diarrhea in early post-operative period. Majority of them had mild form. Half of them recovered with oral rehydration solution, diet modification, folic acid and probiotics. Only one tenth of them had infective in origin and responded to anti-infective therapy. Raised blood tacrolimus trough level was found in one third of LDKT recipients with acute diarrhea; diarrhea improved dramatically after reduction of tacrolimus dose.

Cell cycle arrest biomarkers for the early detection of acute allograft dysfunction and acute rejection in living donor kidney transplantation: a cross-sectional study from Egypt.

Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation. This study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects. IGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)2/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)2/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR. Besides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.

Racial Equity in Living Donor Kidney Transplant Centers, 2008-2018

ImportanceIt is unclear whether center-level factors are associated with racial equity in living donor kidney transplant (LDKT).ObjectiveTo evaluate center-level factors and racial equity in LDKT during an 11-year time period.Design, Setting, and ParticipantsA retrospective cohort longitudinal study was completed in February 2023, of US transplant centers with at least 12 annual LDKTs from January 1, 2008, to December 31, 2018, identified in the Health Resources Services Administration database and linked to the US Renal Data System and the Scientific Registry of Transplant Recipients.Main Outcomes and MeasuresObserved and model-based estimated Black-White mean LDKT rate ratios (RRs), where an RR of 1 indicates racial equity and values less than 1 indicate a lower rate of LDKT of Black patients compared with White patients. Estimated yearly best-case center-specific LDKT RRs between Black and White individuals, where modifiable center characteristics were set to values that would facilitate access to LDKT.ResultsThe final cohorts of patients included 394 625 waitlisted adults, of whom 33.1% were Black and 66.9% were White, and 57 222 adult LDKT recipients, of whom 14.1% were Black and 85.9% were White. Among 89 transplant centers, estimated yearly center-level RRs between Black and White individuals accounting for center and population characteristics ranged from 0.0557 in 2008 to 0.771 in 2018. The yearly median RRs ranged from 0.216 in 2016 to 0.285 in 2010. Model-based estimations for the hypothetical best-case scenario resulted in little change in the minimum RR (from 0.0557 to 0.0549), but a greater positive shift in the maximum RR from 0.771 to 0.895. Relative to the observed 582 LDKT in Black patients and 3837 in White patients, the 2018 hypothetical model estimated an increase of 423 (a 72.7% increase) LDKTs for Black patients and of 1838 (a 47.9% increase) LDKTs for White patients.Conclusions and RelevanceIn this cohort study of patients with kidney failure, no substantial improvement occurred over time either in the observed or the covariate-adjusted estimated RRs. Under the best-case hypothetical estimations, modifying centers’ participation in the paired exchange and voucher programs and increased access to public insurance may contribute to improved racial equity in LDKT. Additional work is needed to identify center-level and program-specific strategies to improve racial equity in access to LDKT.

Time-Varying Determinants of Graft Failure in Pediatric Kidney Transplantation in Europe.

Little is known about the time-varying determinants of kidney graft failure in children. We performed a retrospective study of primary pediatric kidney transplant recipients (younger than 18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure. We report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. One thousand six hundred and thirty-eight recipients experienced graft failure, and 168 died with a functioning graft. Between 2011 and 2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased five-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month post-transplant (adjusted hazard ratio, 0.58; 95% confidence interval, 0.46 to 0.73) and remained statistically significant until 12 years post-transplant. Risk factors for graft failure in the first 2 years were deceased donor younger than 12 years or older than 46 years, potentially recurrent kidney disease, and panel-reactive antibody >0%. Other determinants of graft failure included dialysis before transplantation (until 5 years post-transplant), human leukocyte antigen mismatch 2-4 (0-15 years post-transplant), human leukocyte antigen mismatch 5-6 (2-12 years post-transplant), and hemodialysis (8-14 years post-transplant). Recipients older than 11 years at transplantation had a higher risk of graft failure 1-8 years post-transplant compared with other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of post-transplant time and recipient age showed a higher rate of graft failure during the first 5 years post-transplant in adolescents compared with young transplant recipients. In contrast to deceased donor younger than 12 years, deceased donor older than 46 years was consistently associated with a higher graft failure risk. We report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time post-transplant. The ideal donor age window was dependent on time post-transplant.

Outcome of COVID-19 in Egyptian living-donor kidney transplant recipients and relation to maintenance immunosuppressive drugs: a pilot study

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients is a subject of much debate and became of interest to nephrologists amidst the pandemic. The main concerns are the influence of the chronic use of immunosuppressive drugs, the viral-related risk of acute rejection, and the long-term outcome of allograft function. This single-center prospective study included kidney transplant recipients with COVID-19 infection. Patients were maintained on immunosuppressive regimens. The severity of disease was defined as oxygen saturation < 94%, the need for hospitalization and/or hemodialysis, the occurrence of acute kidney injury (AKI), and mortality. Seventeen patients (54.8%) required hospital admission, four patients needed hemodialysis (12.9%), twelve patients (38.7%) had AKI, and three patients died (9.7%). Oxygen saturation < 94% showed a positive correlation with the presence of diabetes (p value 0.031) and a negative correlation with the maintenance steroid dose (p value 0.046). A negative correlation existed between the need for hemodialysis and average Cyclosporin level (p value 0.019) and between the need for hospitalization and average Tacrolimus level (p value 0.046). Severity of disease was associated with the presence of lymphopenia (p value 0.042), the cumulative steroid dose (p value 0.001), increased serum levels of LDH (p value 0.010), Ferritin (p value 0.020), AST (p value 0.047), and ALT (p value 0.006) and D-dimer levels more than 0.5 mg/L (p value 0.038). This study highlighted that the immunocompromised state of renal transplant recipients may not be regarded as a disadvantage in the setting of COVID-19 infection. Studies on a larger scale are needed to validate these results.

Survival benefit of living donor kidney transplantation in patients on hemodialysis.

Donors bravely donate their kidneys because they expect that living donor kidney transplantation (LKT) confers benefits to recipients. However, the magnitude of the survival benefit of LKT is uncertain. This prospective cohort study used two Japanese nationwide databases for dialysis and kidney transplantation and included 862 LKT recipients and 285,242 hemodialysis (HD) patients in the main model and 5299LKT recipients and 151,074 HD patients in the supplementary model. We employed time-dependent model in the main model and assessed the hazard ratio and the difference in the restricted mean survival time (RMST) between LKT recipients and HD patients. In the main analysis of the main model (LKT, N = 675; HD, N = 675), we matched LKT recipients with HD patients by age, sex, dialysis vintage, and cause of renal failure and excluded HD patients with dementia or performance status grades 2, 3, or 4. The median observational period was 8.00 (IQR 3.58-8.00) years. LKT was significantly associated with a lower risk of mortality (hazard ratios (95% confidence interval (CI)), 0.50 (0.35-0.72)) and an increase in life expectancy (7-year RMST differences (95% CI), 0.48 (0.35-0.60) years) compared with HD. In subgroup analysis, the survival benefit of LKT was greater in female patients than in male patients in the Cox model; whereas older patients gained longer life expectancy compared with younger patients. LKT was associated with better survival benefits than HD, and the estimated increase in life expectancy was 0.48years for 7years.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. In total, 99543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

Pregnancy after deceased donor vs living donor kidney transplant: associated obstetric and graft outcomes

Outside of pregnancy, deceased donor kidney transplant recipients experience worse graft and overall survival compared to living donor kidney transplant recipients. In pregnancy, it is unknown whether the type of donor graft modifies either graft health in the peripartum period or pregnancy outcomes. The objective of this study was to define characteristics and outcomes in pregnancy based on donor type in kidney transplant recipients. Retrospective cohort study of adult kidney transplant recipients who received their graft between 2000-2019 with a subsequent pregnancy enrolled in the Transplant Pregnancy Registry International. The primary outcome was graft loss within 2 years of delivery. Secondary outcomes included severe maternal morbidity and neonatal composite morbidity. Univariate, multivariable logistic regression, and Cox proportional-hazards models were constructed for statistical analysis, with living unrelated donor recipients as the referent. 638 pregnancy outcomes after kidney transplant met our inclusion criteria. Of these, 168 (26.3%) received a graft from a deceased donor (DD), 310 (48.6%) from a living related donor (LR), and 160 (25.1%) from a living unrelated donor (LU). DD recipients were more likely to be nulliparous, have an unplanned pregnancy, and self-identify as non-white. DD recipients were more likely to experience urinary tract infections (DD: 21.8%; LR: 10.1%; LU: 20.6%) (p=0.018). Severe maternal morbidity did not differ by donor type (DD: 3.4%; LR: 2.8%; LU: 7.2%), nor did neonatal composite morbidity (DD: 8.4%, LR: 17.1%, LU: 14.4%). DD transplant was associated with graft loss within 2 years of delivery (DD: 6.7%, LR: 3.7%, LU: 1.3%, aOR: 7.52 [1.53, 60.8]) and long-term graft loss from transplant (aHR: 2.08, [1.10, 3.95]). While our study demonstrates an association between deceased donor transplant and graft loss after pregnancy, it does not provide evidence that pregnancy itself causes graft loss. Deceased donor kidney transplant recipients should not be discouraged from pursuing pregnancy based on their donor type, but these patients should undergo preconception counseling with a discussion of their individualized obstetric and graft risks, close intrapartum monitoring for infection and hypertensive disease, and continued surveillance for at least 2 years postpartum with a multidisciplinary obstetrics and transplant team.

Cancer Risk Following HLA-Incompatible Living Donor Kidney Transplantation.

To characterize cancer risk in ILDKTr, we evaluated 858 ILDKTr and 12 239 compatible living donor kidney transplant recipients (CLDKTr) from a multicenter cohort with linkage to the US transplant registry and 33 cancer registries (1997-2016). Cancer incidence was compared using weighted Cox regression. Among ILDKTr, the median follow-up time was 6.7 y (maximum 16.1 y) for invasive cancers (ascertained via cancer registry linkage) and 5.0 y (maximum 16.1 y) for basal and squamous cell carcinomas (ascertained via the transplant registry and censored for transplant center loss to follow-up). Invasive cancers occurred in 53 ILDKTr (6.2%) and 811 CLDKTr (6.6%; weighted hazard ratio [wHR] 1.01; 95% confidence interval [CI], 0.76-1.35). Basal and squamous cell carcinomas occurred in 41 ILDKTr (4.8%) and 737 CLDKTr (6.0%) (wHR 0.99; 95% CI, 0.69-1.40). Cancer risk did not vary according to donor-specific antibody strength, and in an exploratory analysis, was similar between CLDKTr and ILDKTr for most cancer types and according to cancer stage, except ILDKTr had a suggestively increased risk of colorectal cancer (wHR 3.27; 95% CI, 1.23-8.71); however, this elevation was not significant after correction for multiple comparisons. These findings indicate that the risk of cancer is not increased for ILDKTr compared with CLDKTr. The possible elevation in colorectal cancer risk is unexplained and might suggest a need for tailored screening or prevention.

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients

Hypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use. The aim of this study is to describe the incidence of vasopressor use in LDKT and characterize its effects on allograft function and patient outcomes. This retrospective, observational cohort study included adult patients who underwent an isolated LDKT between August 1, 2017, and September 1, 2018. Patients were divided into those who received perioperative vasopressors and those who did not. The primary objective was to compare allograft function between LDKT recipients that received vasopressors and those who did not. Secondary outcomes included safety endpoints and the identification of clinical variables associated with vasopressor use. A total of 67 patients received an LDKT during the study period. Of those, 25 (37%) received perioperative vasopressors, and 42 (62%) did not. Poor graft function, as defined by the development of slow or delayed graft function, occurred more frequently in patients receiving perioperative vasopressors compared with those who did not (6 [24%] vs 1 [2.4%], P=.016). In multivariable regression modeling, only perioperative vasopressors were statistically significantly associated with poor graft function. In addition, patients exposed to vasopressors experienced more postoperative arrhythmias (8 [32%] vs 1 [4.8%], P=.0025). Using perioperative vasopressors was independently associated with worsened early renal allograft function, including delayed graft function and adverse events in the LDKT population.