Adult Kidney Transplant Recipients Research Articles

The impact of deceased versus living donor graft status on kidney transplant outcomes: A Johannesburg single-center 48 years experience of 1685 patients

Abstract Background This study is aimed to determine the impact of living donor (LD) versus deceased donor (DD) kidney transplantation on renal graft survival and patient overall survival rates within Johannesburg, South Africa. Materials and methods A retrospective assessment was conducted of all 1685 adult first kidney-alone kidney transplant recipients transplanted between the years 1966 and 2013 in a single center. The patients were divided according to the source of the transplant: LD versus DD. Demographics and post-transplantation follow-up data were determined and tabulated. Graft and overall survival plots were generated. Results Of the recipients enrolled, 84.1% were DD recipients and 15.9% were LD recipients. Living donor recipient status was significantly associated with younger age (p ≤ 0.0001), a higher proportion of white, Asian, or mixed race compared to black race (p ≤ 000.1), a higher proportion of urologic etiology of disease (p = 0.015), and a lower proportion with hypertension (p ≤ 0.0001) as the cause of end stage kidney disease. Results showed a decreased risk of graft failure (hazard ratio, 0.55; 95% confidence interval, 0.45–0.66) and a decreased risk of death (hazard ratio, 0.47; 95% confidence interval, 0.36–0.61) among LD graft recipients as compared to DD graft recipients. Conclusions In keeping with internationally reported trends, LD recipients continue to have enhanced patient and graft survival outcomes as compared to DD recipients within our local experience. This Johannesburg experience will serve as a foundation for future related studies in this region of the world.

Immunologic response to SARS-CoV-2 mRNA vaccination in pediatric kidney transplant recipients.

Background COVID-19 disease in kidney transplant (KT) recipients is associated with increased morbidity, mortality, and hospitalization rates. Unfortunately, KT recipients also have a reduced response to SARS-CoV-2 immunization. The primary aim of this study was to assess immunologic response to SARS-CoV-2 mRNA vaccines in pediatric kidney transplant recipients 12–18 years of age. Secondary aims were to assess response rates following a third immunization and determine factors that influence immunization response.MethodsPediatric KT recipients in a single tertiary center received SARS-CoV-2 mRNA vaccination as per local protocol. SARS-CoV-2 immunoglobulin (IgG) was measured following second and/or third vaccination. Demographics including patient factors (age, gender, and underlying disease), transplant factors (time and type of transplant), and immunosuppression (induction, maintenance, and immunomodulatory therapies such as IVIG) were collected from the medical records.ResultsOf 20 participants, 10 (50%) responded following a two-dose vaccine schedule, which increased to 15 (75%) after three doses. Maintenance immunosuppression affected immunologic response, with azathioprine demonstrating a higher rate of response to vaccine compared to mycophenolate (100% vs. 38%, p = 0.04). Increasing prednisolone dose had a negative impact on immunologic response (0.01 mg/kg/day increase: OR 1.60 95% CI 1.01 to 2.57). Tacrolimus dose and trough levels, age, time post-transplant, underlying disease, and other immunosuppression did not impact immunologic response.ConclusionsPediatric KT recipients had similar response rates following SARS-CoV-2 immunization as adult KT recipients. Immunologic response improved following a third immunization. Choice of antimetabolite and prednisolone dosing influenced the rate of response.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary Information Supplementary InformationThe online version contains supplementary material available at 10.1007/s00467-022-05679-y.

Early- and late-onset posttransplant lymphoproliferative disorders among adult kidney and liver transplant recipients.

ObjectivesPosttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients has a high mortality and may present early (<2 years) or late (≥2 years) posttransplantation. We investigated the clinical characteristics of early and late PTLD among kidney and liver transplant recipients.MethodsRecipients, transplanted at Rigshospitalet, with PTLD development as adults from January 2010 to August 2020, were included. Clinical characteristics, laboratory parameters, and pathology of early and late PTLD were compared.ResultsThirty‐one PTLD cases were detected where 10 (32%) were early and 21 (68%) were late PTLD. EBV DNA in plasma was detected in 78% versus 28% in early and late PTLD (p = .037). None of the recipients with early PTLD and nine recipients with late PTLD (47%) had Ann Arbor stage IV at the time of their diagnosis (p = .006). Cyclophosphamid–Hydroxyrubicin–Oncovin–Prednisolon was used for treatment in 10 (48%) recipients with late PTLD (p = 0.032) only. There was no difference in mortality between the two groups.ConclusionsRecipients with late PTLD had a lower prevalence of detectable EBV DNA in plasma, were diagnosed with more advanced disease, and were more frequently treated with chemotherapy compared to recipients with early PTLD.

Human papillomavirus-related cancer risk for solid organ transplant recipients during adult life and early prevention strategies during childhood and adolescence.

Malignancies are among the top three causes of patient death in pediatric and adult kidney transplant (KT) recipients. Solid organ transplant (SOT) recipients, including KT individuals, experience more cancer compared with the general population, including human papillomavirus (HPV)-related anogenital and oropharyngeal cancers. This article describes the epidemiology, pathophysiology and natural history of the HPV infection in both the general population and in SOT recipients, as well as its role in the development of HPV-related pre-cancerous lesions and cancers. Emphasis is given to the primary prevention strategy, HPV vaccination in SOT recipients, and its particularities compared with the general population. Secondary prevention strategies in SOT recipients are discussed and compared with the general population, highlighting cervical cancer screening needs within SOT populations. The article emphasizes how these primary and secondary HPV prevention strategies applied during childhood and adolescence by the pediatric transplant professionals, can lower the burden of HPV-related cancers for SOT recipients in subsequent years, during their adult life.

Durability of Antibody Response after Primary Pneumococcal Double-Dose Prime-Boost Vaccination in Adult Kidney Transplant Recipients and Candidates: 18-Month Follow-Up in a Non-Blinded, Randomised Clinical Trial

Background: Pneumococcal prime-boost vaccination is recommended for solid organ transplant recipients and candidates. The long-term durability of the antibody (AB) response is unknown. The same applies to a dose-dependent immune response. Methods: We studied the durability of the vaccine response after 18 months in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs). Both groups received either a normal dose (ND) or a double dose (DD) of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. The average pneumococcal AB geometric mean concentration (GMC) was evaluated. A level ≥ 1 mg/L was considered protective against invasive pneumococcal disease (IPD). Results: Sixty WLPs and 70 KTRs were included. The proportion of participants protected declined from 52% to 33% in WLPs and from 29% to 16% in KTRs, with the previously significant dose-effect in WLPs no longer present (40% DD vs. 27% ND; p = 0.273). Average pneumococcal AB GMCs remained significantly above baseline levels (all groups p ≤ 0.001). Drug-induced immunosuppression diminished the vaccine dose-effect. Conclusions: At follow-up, the pneumococcal prime-boost vaccination still provided significantly elevated average pneumococcal AB GMCs in both populations. Though the proportion of participants protected against IPD in WLP-DD and WLP-ND were statistically comparable, a DD may still be recommended for WLPs (EudraCT: 2016-004123-23).

Cost-Effectiveness Analysis: Personal Systems Approach in Improving Medication Adherence in Adult Kidney Transplant Patients.

Interventions to improve medication nonadherence in transplantation have recently moved from a focus on motivation and intention, to a focus on person-level quality improvement strategies. These strategies link adherence to established daily routines, environmental cues, and supportive people. The objective of this evaluation was to estimate the cost of implementation and the cost-effectiveness of a person-level intervention shown to increase medication adherence. To estimate the intervention costs, a direct measure microcosting approach was used after key informant interviews with project champions and a review of implementation expenditures. Cost-effectiveness was calculated by comparing the incremental implementation costs and healthcare costs associated with nonadherence to the incremental percent adherent, defined as the percent of patients who took greater or equal to 85% of their medication doses, for each pairwise comparison. The intervention was low-resource to implement, costing approximately $520 to implement per patient, and was associated with significant improvements in medication adherence. These implementation costs were more than outweighed by the expected healthcare savings associated with improvements in adherence. This person-level intervention is a low-cost, efficacious intervention associated with significant statistical and clinical improvements in medication adherence in adult kidney transplant recipients.

Treatment of Epstein-Barr Virus-Related Post-Renal Transplantation Development of Diffuse Large B Cell Lymphoma of the Distal Ureter: A Case Report

Posttransplant lymphoproliferative disorder with involvement of the donor urogenital tissue is a rare and serious complication of solid organ transplant. We report an adult kidney transplant recipient who developed the diffuse large B cell lymphoma of the distal ureter in the setting of new allograft nephropathy. Early intervention, reduction of immunosuppression, surgical reconstruction and chemotherapy salvaged the allograft kidney and averted a fatal outcome. The renal function recovered to the baseline with creatinine ranging between 1.3 and 1.5. The patient did not require dialysis at any point after ureteral stent placement and reconstructive surgery. In addition, the case highlights the importance of multidisciplinary management involving transplant nephrology, oncology, transplant surgery, and urology in such a complicated disease process.

A parallel evaluation of short- and mid-term changes of ambulatory blood pressure in kidney transplant recipients and kidney donors.

Kidney transplantation (KTx) is associated with improved blood pressure (BP) levels for kidney transplant recipients (KTRs) without evoking significant changes in donors. However, there is a paucity of studies offering simultaneous detailed evaluation of BP profiles over time in transplant donor-recipient pairs. The aim of the present study was the parallel evaluation of ambulatory BP levels and trajectories in KTRs and their respective living kidney donors in the short and mid-term following KTx. The study enrolled 40 prospective adult KTRs and their 40 respective donors. All participants were evaluated with 24-h ambulatory BP monitoring (Mobil-O-Graph NG device) at three time points: baseline (1 month before KTx), 3 months and 12 months after KTx. In KTRs, 3-month 24-h systolic BP (SBP) was marginally reduced and 12-month 24-h SBP significantly reduced compared with baseline [131.9±13.3versus126.4±11.9 mmHg (P=.075) and 123.9±10.3 mmHg (P=.009), respectively]. At both the 3- and 12-month time points, 24-h diastolic BP (DBP) was significantly reduced [86.7±11.5versus82.2±8.1 mmHg (P=.043) and 80.3±8.5 mmHg (P=.009)]. Similar observations were made for day- and night time SBP and DBP. Repeated-measures analysis of variance (ANOVA) showed a significant gradual decrease over time in mean 24-h SBP [F(1.463, 39.505) = 3.616; P=.049, partial η 2=0.118] and DBP [F(1.374, 37.089) = 11.34; P=.055, partial η 2=0.116]. In contrast, in kidney donors, 24-h SBP [118.5±11.6versus118.2±12.8 mmHg (P= .626) and 119.2±11.4 mmHg (P=.748)] and DBP did not change at 3 or 12 months compared with baseline; repeated measures ANOVA showed no differences in the mean 24-h SBP and DBP levels over time. The number of antihypertensive agents decreas in KTRs and remained stable in donors. KTx reduces ambulatory BP levels and trajectories in KTRs at 3 months and further so at 12 months post-surgery. Kidney donation does not affect the ambulatory BP levels and trajectories of donors at the same intervals.

MSR59 A Case Study Assessing the Cost-Effectiveness of Maintenance Immunosuppressive Therapy for Kidney Transplantation in Adults: Accounting for Non-Adherence Using Data from a Randomised Trial and the Real World within a Decision-Analytic Model

The aim was to assess the cost-effectiveness of maintenance immunosuppressive therapy among adult kidney transplant recipients, adjusting for patient non-adherence to the prescribed dosing regimens in the ‘real world’.

Impact of a pharmacist-led tacrolimus management protocol in the outpatient setting

BackgroundClinical pharmacists are often used to make recommendations regarding tacrolimus therapy in the post transplant setting.Therapeutic drug monitoring (TDM) of tacrolimus after transplant is based on trough levels in the setting of predetermined institutional immunosuppression goals. To evaluate time within therapeutic range (TTR) of tacrolimus the Rosendaal method can be utilized. ObjectiveOur study aimed to compare objective therapeutic drug monitoring outcomes after the implementation of a pharmacist driven tacrolimus management protocol (postprotocol initiation) with previous management by providers (preprotocol initiation). Practice descriptionThe Ohio State University Wexner Medical Center (OSUWMC) is a 700-bed academic medical center in Columbus, OH. On average, OSUWMC completes more than 300 kidney transplants each year. There are 6 abdominal transplant pharmacists (including one postgraduate year 2 transplant pharmacy resident) that rotate through the inpatient and outpatient setting. Practice innovationA pharmacist-led tacrolimus management protocol in kidney transplant recipients was initiated in October 2018 at our institution, which enabled pharmacists to dose and adjust tacrolimus in the outpatient setting in accordance with prespecified goals. Evaluation methodsThis single-center retrospective analysis included adult kidney transplant recipients on de novo tacrolimus. Patient’s tacrolimus levels were evaluated for 6 months after transplant. The mean tacrolimus percent TTR and the median coefficient of variation (CV) were calculated and compared in postprotocol initiation group (n = 85) with preprotocol initiation group (n = 39). TTR was calculated using the Rosendaal method. ResultsThere was no statistically significant difference between the preprotocol initiation and postprotocol initiation group mean TTR (59.6% vs. 60.5%, P = 0.723), mean CV from 0-3 months after transplant (36.3 vs. 36.0, P = 0.900), and mean CV from at least 3-6 months after transplant (24.5 vs. 22.7, P = 0.351). Rejection rates, development of donor-specific antibodies, and renal function were similar between groups. ConclusionBased on our findings, transplant pharmacists were equally as effective at maintaining tacrolimus percent TTR and CV in the designated kidney transplant recipients included in the management protocol compared with primary management by other transplant providers. The delegation of tacrolimus management to clinical pharmacists is a viable alternative to primary management by outpatient practitioners.

Enhanced Recovery After Surgery Pathway in Kidney Transplantation: The Road Less Traveled.

Background.Enhanced recovery after surgery (ERAS) pathway is a multimodal perioperative care pathway designed to achieve early recovery after surgery. ERAS protocols have not yet been well recognized in kidney transplantation. The aim of this study was to investigate the impact of ERAS pathway on early recovery and short-term clinical outcomes of kidney transplant.Methods.This is a single-center retrospective analysis comparing the outcomes of 20 adult kidney transplant recipients subjected to ERAS pathway with 20 adult recipients operated before ERAS with traditional standard of care.Results.There were no significant differences between both groups regarding age, gender, race, dialysis status, living donor percentage, cold ischemia time, and warm ischemia time. Median hospital stay for ERAS patients was 2 d. Overall median pain scores were significantly lower in the ERAS group versus non-ERAS group (morning after surgery pain score 2 versus 5; peak pain score 4.5 versus 10; lowest pain score 0 versus 2; P = 0.0001). ERAS patients had earlier ambulation (walking) and oral nutrition (regular diet) (first versus second day postoperatively in traditional group). Earlier bowel movement was observed in ERAS patients. There were no significant differences in graft function or 30-d readmission rates between both groups.Conclusions.Implementation of ERAS pathway in kidney transplantation is feasible. Using ERAS is associated with less pain, earlier ambulation and advancement of oral nutrition, and short hospital stay.

Health Facts Medication Adherence in Transplantation (H-MAT) Study: A Secondary Analysis of Determinants and Outcomes of Medication Nonadherence in Adult Kidney Transplant Recipients

Aims To explore the relationship between determinants and posttransplant medication nonadherence (MNA) in adult kidney transplant recipients, and to examine the relationship between posttransplant MNA and clinical outcomes. Methods Using the World Health Organization's model, this retrospective, multicenter, correlational study examined the relationship between determinants, posttransplant MNA, and clinical outcomes in 16,671 adult kidney transplant recipients from the Cerner Health Facts national data warehouse. Results With 12% MNA, those who were nonadherent were more likely to have the social/economic factors of being younger, single, Caucasian versus Hispanic race, have the condition-related factor of mental health/substance use disorder, and have the healthcare system-related factor of government/health maintenance organization/managed care insurance (p′s < 0.05). Bivariate correlations indicated both age (OR = 1.006, p=0.01) and mental health or substance use disorder diagnosis (OR = 1.26, p=0.04) were significant predictors of MNA. Patients were 0.6% more likely to be medication adherent for each year they increased in age and 26% more likely to be MNA if they were diagnosed with a mental health/substance use disorder. Nonadherent patients were less likely to be readmitted, but more likely to have complications after transplant and medication side effects (p′s < 0.01). Conclusions Using one of the largest samples of adult kidney transplant patients, our findings support the WHO model and move the body of medication adherence intervention research forward by clarifying the importance of focusing interventions not only on the patient but on multilevel determinants. Consistent with previous studies, MNA negatively impacts transplant outcomes.

Outcomes of kidney transplantation in patients with myeloma and amyloidosis in the USA.

Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. Among 168 369 adult first kidney transplant recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67-2.99] and aHR 1.40 [95% CI 1.08-1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37-2.53) versus aHR 1.16 (95% CI 0.89-1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91-2.56) and aHR 1.30 (95% CI 1.03-1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD.

A comparison of four established GFR formulas to estimate measured GFR and changes in GFR in adult kidney transplant recipients

The accurate assessment of glomerular filtration rate (GFR) is important in the follow-up of kidney transplant recipients in order to identify graft dysfunction. A number of formulas have been proposed to calculate GFR from endogenous plasma markers such as creatinine or cystatin C since measuring GFR using exogenous markers is troublesome. This study compares and evaluates the ability of four different GFR formulas to estimate kidney graft function and to detect changes in GFR in kidney transplant recipients. The study included patients from the prospective, multicenter CONTEXT trial in kidney transplant recipients. GFR was measured using plasma clearance of 51Cr-EDTA and estimated using the MDRD, CKD-EPI Creatinine, CKD-EPI Cystatin C and CKD-EPI Cystatin C + Creatinine equations at three (n = 83) and twelve (n = 65) months post-transplantation. For each formula mean bias, precision, and accuracy were evaluated. The MDRD equation had the lowest mean bias (0.2 ml/min/1.73 m2), whereas the CKD-EPI Cystatin C + Creatinine equation had the highest precision (8 ml/min/1.73 m2). Accuracy at three months were similar for all equations (P30 > 80%) except for the CKD-EPI Cystatin C equation, which performed poorer (P30 = 55%). None of the formulas evaluated avoided misclassification of changes in GFR. The most optimal combination of precision and accuracy suggests the use of CKD-EPI Creatinine + Cystatin C equation in kidney transplant recipients.

COVID-19 Disease in Kidney Transplantation Recipients: A Single-Center Study (Experience of Dr. Shariati Hospital)

Background: Coronavirus disease 2019 (COVID-19 disease) is caused by SARS-CoV-2. In December 2019, several outbreaks of severe and life-threatening pneumonia with unknown organism were reported in Wuhan, China and the disease spread rapidly all over the world and caused the biggest pandemic. There was no clear information regarding incidence, morbidity, and mortality rate of COVID-19 disease in kidney transplant recipients or other solid organ transplant recipients. Therefore, we designed a study to evaluate the factors that can have any impact on kidney transplant recipients infected with SARS-Cov2.&#x0D; Methods: Our research was a retrospective cross-sectional study. The study population was all adult kidney transplant recipients (&gt; 18 years old) who were hospitalized due to COVID-19 disease according to national guidelines from 1st March, 2020 to 20th April, 2020 in Shariati Hospital, Tehran, Iran. Demographic data, common clinical complaints, vital signs, types and dose of immunosuppressive drugs, comorbidity diseases, and basic laboratory tests were extracted from the medical records using a data collection form.&#x0D; Results: According to the results of our investigation, mortality rate was 69.2% in kidney transplant recipients who were admitted in our hospital. No one died under the age of 47 years, while no one survived over the age of 58 years. As a result, age can be a reliable predictor of survival rate in kidney transplant recipients with COVID-19 pneumonia. All patients in non- survivors’ group were elderly and needed intubation, mechanical ventilation, and renal replacement.&#x0D; Conclusion: In addition to early referral and early start of appropriate and specific treatments of COVID-19 in patients with kidney transplantation, our general advice, is discontinuation of antimetabolite drugs at admission time, dose reduction of calcineurin inhibitors, and even withdrawal of all immunosuppressive drugs except steroids in critical cases.

The first experience of cord blood stem cells application in kidney transplantation: A descriptive study

Abstract. Kidney transplantation is recognized as the optimal method of end-stage kidney disease treatment, but chronic renal allograft rejection remains an unresolved issue and leads to transplanted organ function loss. Recent studies show positive effects of stem cell injections in a variety of diseases, including kidney transplantation.&#x0D; The present study aimed to analyze the first experience of umbilical cord blood stem cells application in living-related kidney transplantation in Shalimov’s National Institute of Surgery and Transplantation, give a preliminary assessment of their effectiveness and safety, evaluate the clinical course and especially the dynamics of laboratory parameters in the recipient’s postoperative period.&#x0D; Methods. The study group included 6 male, adult recipients of kidney transplants, who performed the first kidney allotransplantation from a living family donor in the Shalimov’s National Institute of Surgery and Transplantology in 2020 – 2021. Before surgery, all patients received intravenous administration of a fraction of nuclear cells from human umbilical cord blood at a dose of 2-3 x 106/kg body weight in combination with standard three-component immunosuppressive therapy. Immune system studies were performed before kidney transplantation, on the first and third days of the postoperative period, at the end of the first and second week, as well as on the first, third, sixth, and twelfth months, following kidney transplantation. Renal graft function was assessed by serum creatinine and glomerular filtration rate. Monitoring of clinical and laboratory parameters of blood and urine, the concentration of calcineurin inhibitors (C0) was carried out regularly three times a week for the first month, twice a month for 2-3 months, and once a month until the end of the year.&#x0D; Puncture biopsy of the transplanted kidney was performed three months after surgery to diagnose the pathology of the graft, namely the manifestations of acute and chronic rejection, the nature and degree of which were determined according to the Banff classification.&#x0D; The state of the immune system of the recipients was characterized by indicators of cellular and humoral immunity.&#x0D; Statistical processing of research results was performed using the statistical package StatSoft (2010) STATISTICA 9.1 for Windows StatSoft Inc, Tusla.&#x0D; Results. All patients received cord blood stem cells without complications. On the first day after surgery, an average diuresis was 9415 ± 928.1 ml. Normalization of graft function was observed on the second or third day (GFR more than 90 ml/ min/1.73 m2). There were no rejections of grafts and signs of opportunistic infections in the patients during 1 year follow-up period. Morphological studies did not reveal signs of significant pathological changes in transplanted kidneys in patients who received stem cells as induction therapy.&#x0D; The study of the state of the immune system of recipients in the dynamics, given the insufficient number of patients, requires further research.&#x0D; Conclusions. The administration of cord blood stem cells to recipients prior to kidney transplantation is safe and promotes rapid recovery of renal allograft function. There were no signs of morphological proven chronic graft rejection, which allows us to predict its long-term functioning in the future. To assess the response of the recipient's immune system to the application of cord blood stem cells requires the accumulation of additional data.

Nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) +/- ipilimumab (IPI) for kidney transplant recipients (KTR) with advanced cutaneous cancers.

9507 Background: Cancer is a leading cause of death among KTR, but these patients (pts) have been excluded from trials of immune checkpoint inhibitors due to immunosuppression and risk of allograft loss. We report findings from the first prospective clinical trial of NIVO + TACRO + PRED +/- IPI in KTR with selected advanced cutaneous cancers. Methods: The primary composite endpoint was lack of tumor progression per RECIST v1.1 without allograft loss at 16 weeks (W) on NIVO. Adult KTR with advanced melanoma, basal, cutaneous squamous, or Merkel cell carcinoma (MEL, BCC, CSCC, MCC), for whom non-immune therapies were insufficient were eligible. Immunosuppression was standardized to low-dose TACRO (goal trough 2-5 ng/mL) + PRED 5mg daily; pts then received NIVO 480mg IV q4W. Pts with progressive disease (PD) could receive NIVO 3mg/kg + IPI 1mg/kg IV q3W x 4 followed by NIVO 480mg IV q4W. Donor-derived cell-free DNA (dd-cfDNA) levels were measured q2W as a potential predictor of allograft rejection. Results: From 11/2019 - 4/2021, of 12 pts enrolled, 8 pts with CSCC, MCC or MEL were evaluable for response (Table). All pts experienced PD on NIVO; treatment-related allograft loss (TRAL) occurred in 1 pt. 6 pts then received IPI + NIVO. Responses: 2 (33%) with marked tumor regression at 6W and eventual complete response (CR; 1 with TRAL), and 4 (67%) with PD (1 with TRAL). 7/8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. Only 2/5 on-NIVO biopsies demonstrated moderate immune infiltrates; both of these pts later developed a CR to IPI + NIVO. Rejecting allografts contained dense immune responses (plasma cells, CD4+ &amp; CD8+ lymphocytes, PD-1+ lymphocytes, macrophages, PD-L1+ glomerular endothelium, and focal PD-1 &amp; PD-L1 positivity in renal tubules). In 2/3 pts with TRAL, elevations in dd-cfDNA levels occurred 10 and 15 days earlier than increases in weekly serum creatinine levels. TRAL #3 occurred after discontinuation of study therapy (including TACRO) and dd-cfDNA monitoring. Conclusions: In KTR receiving low-dose TACRO + PRED, NIVO augments tumor immune cell infiltration in some pts but is insufficient to mediate tumor regression. Adding IPI can enhance anti-tumor immunity and mediate tumor regression. TACRO + PRED was insufficient to prevent allograft rejection after PD-1 +/- CTLA-4 blockade in 2/8 pts. In pts with TRAL, increased dd-cfDNA levels preceded increased serum creatinine. Based on these findings, we are modifying the trial therapy regimen to augment anti-tumor immunity and preserve allograft function. Clinical trial information: NCT03816332. [Table: see text]

Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.

This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P < 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P < 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P < 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P < 0.001) and peri-tubular capillaritis (r = 0.344, P < 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.

Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded, randomized clinical trial

BackgroundPneumococcal prime-boost vaccination is recommended for solid organ transplant recipients, but is not thoroughly tested in this population. Furthermore, a pneumococcal vaccine dose effect has never been investigated, though observed in healthy adults. To assess whether a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) increases the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs), a phase 3, randomized, non-blinded trial was conducted. MethodsKTRs and WLPs were in parallel groups assigned either normal or double dosage of both vaccines 12 weeks apart. A ′protective response′ was an average geometric mean concentration ≥ 1 mg/L based on 12 vaccine shared serotype-specific IgG antibodies. Furthermore, number of antibodies with ≥ 2-fold rises and individual serotype-specific antibody concentrations were evaluated. Follow-up was 48 weeks. ResultsSeventy-four KTRs and 65 WLPs were enrolled. In WLPs, double dosage resulted in a significantly higher proportion of participants with a ′protective response′ (66.7%), 5 weeks after PPV23, compared to normal dosage (35.5%), p = 0.015. KTRs exhibited no dose effect. After PPV23, all four groups had increased their number of serotypes with ≥ 2-fold rises (p ≤ 0.05 for both WLPs groups; p ≤ 0.01 for both KTRs groups). Vaccines were safe, well tolerated and still immunogenic at week 48. ConclusionsData suggests that double dosage of pneumococcal vaccines used according to the prime-boost strategy might be recommendable for WLPs. Furthermore, our data supports PPV23́s additive effect to PCV13 in KTRs and WLPs. (EudraCT: 2016–004123-23)

Retrospective analysis of the impact of severe obesity on kidney transplant outcomes.

The prevalence of obesity among kidney transplant recipients is rising. We sought to determine the association between recipient body mass index (BMI) and post-transplant complications. Single-center, retrospective cohort study of all adult kidney transplant recipients from 2004 to 2020. Recipients were stratified into four BMI categories: normal-weight (BMI 18.5-24.9kg/m2, n=1020), overweight (BMI 25-29.9kg/m2, n=1002), moderately obese (BMI 30-34.9kg/m2, n=510) and severely-to-morbidly obese (BMI≥35kg/m2, n=274). Logistic regression was used to estimate the association between BMI category and surgical site infections (SSIs). Recipients with BMI≥35kg/m2 had significantly higher rates of SSIs (P<.0001) compared with recipients in all other categories. On multivariable analysis, recipients with BMI≥35kg/m2 had increased odds of SSIs compared with normal-weight recipients [odds ratio (OR) 3.34, 95% confidence interval (CI) 1.55-7.22, P=.022). On multivariable and Kaplan-Meier analyses, no BMI groups demonstrated increased odds for death-censored graft failure. Severe obesity in kidney transplant recipients is associated with increased SSIs, but not kidney allograft failure.