Kidney Transplant Population Research Articles

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.

#5940 CLINICAL UTILITY OF GENETIC TESTING IN A KIDNEY TRANSPLANT CLINIC

Abstract Background and Aims Inherited kidney disease (IKD) is one of the leading causes of end-stage of kidney disease. Genetic diagnosis plays an important role in the counseling and management of kidney transplant patients or those on the waiting list, as it makes it possible to identify the cause of CKD, help in the selection of living donors, carry out genetic counseling and find out the prognosis around the graft survival and the risk of recurrence of the primary disease. The objective of the following study is to analyze the prevalence of IKD in our kidney transplant population and those on the waiting list, the phenotypic characteristics, genetic findings, and the diagnostic reclassification performed after the genetic study. Method This retrospective study has incluyed all genetic test (by next-generation sequencing (NGS) until 529 genes associated with kidney disease) performance between January 2018 and January 2023 in kidney transplant patients or on the waiting list for kidney transplant at Doctor Peset Hospital, using a multidisciplinary team approach. The patients were considered for genomic evaluation if they met one of the inclusion criteria: CKD of unknown etiology, family history of CKD, glomerular disease or chronic tubulo–interstitial disease with no recognized cause, suspicion of aHUS, CKD and other extrarenal syndromic signs or with renal malformations or nephrocalcinosis. Demographic data, family burden and screening, CKD phenotype, urinary anormalities, hypertension, diabetes, results of genetic test, were analyzed. Results We performed genetic testing in 76 patients (43,4% women; 88% Caucasian). Median age at time of kidney failure was 37 years (range: 17–77), 62% of patients had a positive family history of CKD and 29% presented extrarenal manifestations. The majority were male patients (56.6%) and Caucasian patients (88.2%). Most patients presented with an original clinical diagnosis glomerular disease 52,6% (FSGS lesion on biopsy (8/27) and non-diagnostic histology (10/27)), followed by ciliopathy (13%), aHUS (10.5%), and chronic kidney disease of unknown cause (6.6%), tubulointerstitial nephritis (6.6%), and with congenital anomalies (6.6%). In 46 patients had a genetic diagnosis defined as finding a pathogenic or likely pathogenic gene variant that explained the patient's kidney disease. With majority being COL4 variants (26.3%), followed by autosomal dominant polycystic kidney disease (ADPKD) (10.5%), podocytopathy and autosomal dominant tubulointerstitial kidney diseases. There were confirmed within a clinical diagnostic in 28% (above all ADPKD) and resulted in reclassification of the clinical diagnosis in 33% (above all COL4-related nephropathy) and there are more frequently a negative result if clinical diagnosis was unknown etiology, congenital anomalies o aHUS until 60%. With this data, 78% of the patients could have avoided a biopsy and 50% a immunossuppresive treatment with the diagnosis by genetic test. A genetic cause was identified by family screening in 16 families comprising 19 patients. A genetic diagnosis were more likely to have a family history of kidney disease (47,4% versus 14,5%, P < 0.001). There was otherwise no statistically significant difference in any other clinical characteristic (age at onset of kidney disease, age at kidney failure, race, hypertension, diabetes, hematuria, renal cyst or stone). Conclusion Our study demonstrates the clinical utility of genetic study in kidney transplants with unknown etiology or glomerulonephritis or chronic tubule-interstitial disease with no recognized cause or with positive family history of kidney disease, getting a genetic diagnosis until 60%, with a reclassification of the clinical diagnosis in a one-third. A genetic diagnosis is necessary to evaluate to kidney transplant recipients, to identify the etiology of CKD, to perform a genetic counseling and to improve patient management and prognosis.

#5465 RACE-FREE EGFR EQUATION IN KIDNEY RECIPIENTS: A DEVELOPMENT AND VALIDATION STUDY

Abstract Background and Aims To assess the performances of the current eGFR equations, including the race-free CKD-EPI-2021, in the kidney transplant population, and compare these performances to a race-free kidney-recipient-specific (KRS) GFR equation. Method We included adult kidney recipients transplanted between 01/01/2000 and 01/01/2021 in 17 academic cohorts in Europe, the USA and Australia comprising 14 transplant centres and three clinical trials. Measured GFRs (mGFR) were assessed using 51Cr-EDTA, 99Tc-DTPA, inulin, iothalamate or iohexol clearance, according to the local practice. A KRS GFR equation was developed using additive and multiplicative stepwise linear regressions and its performance was compared to those of the current GFR equations. The performances were assessed with the P30 and the correct classification of chronic kidney disease (CKD) stage metrics. Results The study included 15 489 patients, having 50 464 GFR values both measured and estimated by creatinine-based equations. Among the current GFR equations, race-free CKD-EPI-2021 equation showed the lowest performance compared with MDRD and CKD-EPI-2009 equations. We then built a race-free KRS GFR equation based on an additive model including creatinine, age, and sex. We showed that using race did not increase the performance of the equation. We found that the race-free KRS GFR equation showed significantly improved performance compared with the race-free CKD-EPI-2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). Finally, we showed that the race-free KRS GFR equation performed well in a series of kidney transplant recipient subpopulations stratified by race, sex, age, body mass index, donor type, therapeutics, creatinine and GFR measurement methods and timing. Based on these results we developed an online application that estimates GFR based on recipient age, sex and creatinine: https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/ Conclusion Using multiple, international cohorts of kidney recipients, we developed and validated a new race-free KRS GFR equation that demonstrated high accuracy and outperformed the race-free CKD-EPI-2021 equation developed in individuals with native kidneys.

#5711 MYOCARDIAL PERFORMANCE EVOLUTION AT 6 MONTHS FROM COVID-19 IN CKD PATIENTS

Abstract Background and Aims COVID-19 is associated with myocardial injury and in previous studies, patients with right ventricular dysfunction had an increased risk of all-cause death. In the general population, there is evidence that right ventricular strain improves at 6 months after COVID-19, but data about the course of other myocardial performance parameters are limited. Method CARDIO-SCARS in CKD is a currently ongoing observational cohort study that aims to assess the cardiovascular risk in a CKD (stages 3 to 5), dialysis and kidney transplant population following SARS-CoV2 infection, by using clinical evaluation, various techniques and both endothelial dysfunction and myocardial injury biomarkers (ClinicalTrial.gov Identifier NCT05125913). We hereby report the evolution of the main echocardiographic myocardial performance parameters at 6 months from COVID-19 disease. Results Our study included 222 patients (134 in the COVID-19 group and 88 in the control group). In the COVID-19 group, the echocardiography was performed at a mean distance of 2.21±1.9 months after testing positive for SARS-CoV-2. The mean age at baseline was 58.81±15.2 years and 53.41±14.14 years for the COVID-19 group and control group respectively. Atrial fibrillation, heart failure, ischemic heart disease and diabetes were more prevalent in the COVID-19 group. When analyzing the mean absolute difference between baseline and 6 months echocardiographic parameters using a two-sample t-Test, statistically significant results were observed for the left ventricular (LV) ejection fraction (EF), LV Tei Index, right ventricular (RV) Tei Index and RV free wall longitudinal strain (RVFWLS) as follows: Δ LVEF was 0.70±7.97% and -2.44±7.30% (p = 0.005), ΔLV Tei index was -0.04±0.19 and 0.0007± 0.11 (p = 0.024), Δ RV Tei index was -0.04±0.17 and 0.009±0.20 (p = 0.034) and ΔRVFWLS was -1.68±4.36% and -0.32±3.34% (p = 0.039) for the COVID-19 group and the control group respectively. Conclusion Our study is the first to describe the evolution of echocardiographic parameters post-COVID in a CKD population. Despite worse demographic and echocardiographic characteristics at baseline, patients from the COVID-19 group had a better evolution at 6 months, when compared to the control group. Both right and left ventricular myocardial performance indices improved for the COVID-19 patients and worsened for the control group.

#5620 MAPPING OUT THE RESEARCH FIELD OF PROGNOSTIC MODELS IN NEPHROLOGY: A SCOPING REVIEW

Abstract Background and Aims Prognostic models can support individualized care provision and well-informed shared decision-making. Although there has been an upsurge of prognostic research in the field of nephrology, the uptake of prognostic models remains limited. A broad overview of the field is needed to see where we currently stand, and how to progress from here. With this overview we can identify current knowledge gaps, and potential implementation opportunities. Moreover, it will provide guidance as to where future research should be directed. Therefore, the aim of this study was to map the body of existing prognostic models within nephrology and detail the range in outcomes and populations that they cover, as well as their methodological rigour. To do so, we performed a scoping review of studies developing, validating or updating a prognostic model for patients with chronic kidney disease (CKD) or those receiving kidney replacement therapy (KRT). Method A framework for scoping reviews by Arksey and O'Malley was used and the PRISMA extension for Scoping Reviews was adhered to for transparent reporting. A systematic search in PubMed and Embase was performed to identify relevant studies that describe prediction models for patients with CKD or those on KRT. Studies were screened for their relevance based on prespecified criteria, and data was extracted on general characteristics of the included studies and their reporting and methodological quality. For the studies in which a prognostic model was developed, model presentation (e.g., full regression formula or risk score), whether validation strategies were employed, and model type (regression modelling vs machine learning), were extracted. Finally, we extracted data on the predicted outcome definitions, and which models were validated and/or updated most often. Descriptive statistics were used to summarise all findings. Results The systematic search yielded 3728 studies for screening, of which 596 were finally included. Of these, 29.5% concerned a CKD population, 31.4% a dialysis population, and 39.1% a kidney transplantation population. Many studies had a sample size of less than 500 participants (41.4%). Although a measure of discrimination of the model was usually presented (79.5%), a measure of calibration was presented in less than half of the studies (43.5%). Of the 411 studies in which a prognostic model was developed, most performed only internal validation (57.9%) or no validation at all (27.7%). Moreover, in almost half of the development studies (45.3%) no usable version of the model was reported, meaning that insufficient information was reported to apply the model in a new setting. For CKD populations, the majority of models predicted disease progression (n = 78), followed by models predicting mortality (n = 22) and cardiovascular events (n = 13). For dialysis populations, most models predicted mortality (n = 79), cardiovascular events (n = 20), and vascular access related outcomes (n = 15). Finally, models originally developed for kidney transplantation populations mainly predicted graft survival (n = 59), recipient survival (n = 39), and delayed graft function (n = 24). Models for non-traditional clinical outcomes, like health-related quality of life and symptom burden, were scarce. If validated or updated at all (n = 199), most models (n = 123) were externally validated and/or updated only once. The rest (n = 76) were validated and/or updated more, with a median (IQR) of 2 (2-3), 2 (2-3), and 3 (2-4) within the CKD, dialysis, and transplantation populations, respectively. Conclusion A substantial amount of nephrological prognostic research has been performed, but to minimize the gap between research and patient care additional steps have to be undertaken. Methodological rigour, external validation, updating, and impact assessment are of paramount importance. In addition, the current body of literature focusses on traditional clinical outcomes, and models for patient-reported outcomes are scarce. Opportunities to improve implementation of prognostic models in nephrological care are described in Box 1.

#4150 INTERNATIONAL COMPARISON AND TIME TRENDS OF FIRST KIDNEY TRANSPLANT RECIPIENT CHARACTERISTICS ACROSS EUROPE: A STUDY FROM THE ERA REGISTRY

Abstract Background and Aims Large international differences exist in the kidney transplantation (KT) rate across Europe. Countries might transplant a different group of end-stage kidney disease (ESKD) patients, but up to now an overview of recipient characteristics in first kidney transplant recipients in the different European countries is lacking. Therefore, the aim of this study was to give an overview as well as time trends in age, sex and primary renal disease (PRD) distribution of first kidney transplant recipients in Europe. Method The European Renal Association (ERA) Registry database was used to obtain data on adult patients receiving their first KT 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. The first KT rate was calculated by dividing the number of first KTs by the adult general population counts and multiplied by one million. Results In total, 99,543 patients received a first KT between 2010 and 2019 for all countries combined. The percentage of recipients aged 65 years and older varied greatly between countries, with Bosnia and Herzegovina having the lowest percentage (1%), and the Netherlands, Spain and Norway having the highest percentages (>25%). Similar results were found for deceased donor first KT, but for living donor first KT Spain was no longer among the countries with the highest percentage of recipients aged 65 years and older. The percentage of female recipients ranged between 33% in Austria and 38% in the Netherlands for total first KT, between 33% in Austria and 38% in Denmark for deceased donor first KT and between 30% in Austria and 39% in the United Kingdom for living donor first KT. When comparing the distribution of PRDs, Bosnia and Herzegovina had a relative high percentage of recipients with glomerulonephritis (35%), while Finland had a high percentage of recipients with diabetes mellitus (29%) and the Netherlands and Norway a high percentage of recipients with hypertension / renal vascular diseases (17% and 22% respectively). This distribution was similar for deceased and living donor first KT recipients. Over time, the most prominent change regarding the recipient characteristics was observed for the age of the recipient, with an increasing proportion of recipients aged 65 years and older from 18% in 2010 to 28% in 2019 for all countries combined, and with a similar trend observed in most countries. Conclusion We observed large differences in the recipient characteristics at first KT between European countries and over time, especially for the recipient age and PRD. These new insights in the distribution of recipient characteristics in the first KT population could elucidate which ESKD patients receive a KT.

#2702 ANALYSIS OF IMMUNOSUPPRESSANT ADHERENCE, TREATMENT PREFERENCES AND NEEDS, AND MENTAL HEALTH DISORDERS IN THE POST-TRANSPLANTATION PERIOD

Abstract Background and Aims Medical treatment after kidney transplantation is not enough to assure optimal outcomes due to emotional factors that contribute on graft survival. To incorporate patient´s treatment preferences in clinical practice improves health outcomes. Few is known about treatment preferences and needs of kidney transplant population. The aims of the study were to quantify mental health disorders prevalence, immunosuppressive adherence, treatment preferences and needs of Spanish kidney transplant patients in post-transplantation period. Method Transversal-observational study in stable kidney transplant patients from one center in Madrid-Spain. Demographics, social-clinical variables, validated questionaries for anxiety, depression, stress, resilience, life satisfaction and quality of life related with health, and an ad-hoc survey of treatment preferences and needs were applied. Results A total of 116 patients were included, 25% had mental health pathology before transplant. Mental health disorders prevalence for depression, anxiety and stress were 26%, 27% and 23.3% respectively. Life satisfaction screening revealed only 29% of patients very satisfied with life. Patients with lower scores in mental health tests were significatively related with poor immunosuppressive adherence (P = .004). Treatment preferences and needs identified were how to improve physical condition (47%), information for anxiety and/or depression management (37%), and to receive psychological therapy from Nephrology Service (95%). See Table 1 and 2 for results. Conclusion Mental health disorders prevalence in Spanish kidney transplanted patients were high and had a negative impact in immunosuppressive adherence. This demands a biopsychosocial, interdisciplinary, focused on patient´s treatment preferences approach, individually and in groups from Nephrology Service.

Scientific Review of the Knowledge Gap in the Efficacy of Antiviral Therapy to a Low-Risk Kidney Transplant Population Cohort

Scientific Review of the Knowledge Gap in the Efficacy of Antiviral Therapy to a Low-Risk Kidney Transplant Population Cohort

Immunologic Outcomes in Cross-Sex Solid Organ Transplants: A Systematic Review and Meta-Analysis to Inform Vascularized Composite Allotransplantation.

Of nearly 90 hand and 50 face transplant recipients, only five have received a cross-sex vascularized composite allotransplantation (CS-VCA). CS-VCA has the potential to expand the donor pool and has been proven anatomically feasible and ethically acceptable in previous studies. However, there is a lack of immunologic data. This study evaluated the immunologic feasibility of CS-VCA through analysis of the solid organ transplant literature, given the paucity of CS-VCA data. The authors hypothesize that rates of acute rejection (AR) and graft survival (GS) in CS versus same-sex (SS) solid organ transplantation are similar. A systematic review and meta-analysis were performed. Studies comparing GS or AR episodes in CS and SS adult kidney (KT) and liver transplant (LT) populations were included. Odds ratios were calculated for overall GS and AR for all SS and CS transplant combinations [male-to-female (MTF), female-to-male, and overall]. A total of 693 articles were initially identified with 25 included in the meta-analysis. No significant difference in GS was noted between SS-KT versus CS-KT [OR, 1.04 (95% CI, 1.00 to 1.07); P = 0.07), SS-KT versus MTF-KT [OR, 0.97 (95% CI, 0.90 to 1.04); P = 0.41), and SS-LT versus MTF-LT [OR, 0.95 (95% CI, 0.91 to 1.00); P = 0.05). No significant difference in AR was noted between SS-KT versus MTF-KT [OR, 0.99 (95% CI, 0.96 to 1.02); P = 0.57), SS-LT versus CS-LT [OR, 0.78 (95% CI, 0.53 to 1.16); P = 0.22], or SS-LT versus female-to-male LT [OR, 1.03 (95% CI, 0.95 to 1.12); P = 0.47]. For the remaining pairings, GS was significantly increased and AR was significantly decreased in the SS transplants. Published data suggest immunologic feasibility of CS-KT and CS-LT with the potential for generalization to the VCA population. In theory, CS-VCA could expand the potential donor pool, ultimately leading to decreased wait times for recipients and improve the likelihood of establishing a immunologically favorable donor-recipient match.

Frailty and sarcopenia in older kidney transplant recipients: a cross-sectional study

The aging of the kidney transplant population is accelerating, and measures against geriatric syndromes including frailty and sarcopenia, which elevate the risk of needing long-term care and even death, are being considered important. Recently, both the frailty and sarcopenia criteria for Asians were revised based on various research reports and clinical experiences. The purpose of this study is twofold: firstly, to investigate the prevalence of frailty based on the revised Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Kihon Checklist (KCL) and that of sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) 2019 as well as the relationship between frailty and sarcopenia, and secondly, to determine the concurrent validity of the KCL with the revised J-CHScriteria in older kidney transplant recipients. This study was a single-center cross-sectional investigation carried out on older kidney transplant recipients who visited our hospital from August 2017 to February 2019. The diagnosis of frailty was assessed using the revised J-CHS criteria and the KCL. The diagnosis of sarcopenia was made by low skeletal muscle mass and either low physical performance or low muscle strength based on the AWGS 2019. To examine the relationship between frailty and sarcopenia, categorical variables were compared using chi-squared test and continuous variables Mann-Whitney U test. Spearman's correlation analysis was used to investigate the correlation between the KCL score and the revised J-CHS score. The concurrent validity of the KCL for estimating frailty based on the revised J-CHS criteria was evaluated using the receiver operating characteristics (ROC) curve analysis. A total of 100 older kidney transplant recipients were enrolled in this study. The median age was 67, 63 (63%) were males, and the median time after transplant was 95months. The prevalence of frailty based on the revised J-CHS criteria and the KCL, and sarcopenia based on the AWGS 2019 was 15%, and 19%, and 16% respectively. Sarcopenia was significantly associated with frailty based on the KCL (p = 0.016), while not with frailty based on the revised J-CHS criteria (p = 0.11). The KCL score significantly correlated with the revised J-CHS score (p < 0.001). The area under the ROC curve was 0.91. Frailty and sarcopenia are interrelated complex geriatric syndromes that are risk factors for adverse health outcomes. In older kidney transplant recipients, frailty and sarcopenia were highly prevalent and frequently co-existed. Furthermore, the KCL was verified as a useful tool for frailty screening in these patient. Easy identification of patients with frailty, which is reversible, can help clinicians institute appropriate corrective measures for kidney transplant recipients to improve transplant outcomes.

Pegloticase efficacy and safety in kidney transplant recipients; results of the phase IV, open-label PROTECT clinical trial.

Kidney transplant (KT) recipients have a high prevalence and severity of gout. Pegloticase (pegylated recombinant uricase) rapidly metabolizes serum uric acid (sUA), and its efficacy is not impacted by kidney function. This open-label, Phase 4 trial (PROTECT NCT04087720) examined safety and efficacy of pegloticase in 20 participants with KT>1 year prior to enrollment and with uncontrolled gout (sUA ≥7mg/dL, intolerance/inefficacy to urate lowering therapy, and ≥1 of the following: tophi, chronic gouty arthritis, ≥2 flares in past year) and functioning KT (estimated glomerular filtration rate [eGFR] ≥15mL/min/1.73 m2 ) on stable immunosuppression therapy. The primary endpoint was sUA response during month 6 (sUA<6mg/dL for ≥80% of time). The study enrolled 20 participants (mean±SD); age: 53.9±10.9 years, time since KT: 14.7±6.9 years, sUA: 9.4±1.5mg/dL, gout duration: 8.4±11.6 years; all on ≥2 stable doses of immunosuppression agents. Pegloticase (8mg intravenous every 2weeks) in KT recipients with uncontrolled gout showed a high response rate of 89% (16/18 responders). Two participants discontinued treatment solely due to COVID-19 concerns prior to month 6 were not included in the primary analysis. Pegloticase exposures were higher than those historically observed with pegloticase monotherapy, and no anaphylaxis or infusion reaction events occurred during the study. This improved response rate to pegloticase in the KT population reflects observations from other trials and reports on immunomodulation with pegloticase. As the KT population has a high prevalence of gout and limitations with oral urate lowering medication options, these findings suggest a potential option for uncontrolled gout therapy in KT participants.

An automated histological classification system for precision diagnostics of kidney allografts.

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .

Cytopenias in pediatric kidney transplant recipients: preceding factors and clinical consequences.

Kidney trans plantation is associated with secondary complications, including the risk of developing posttransplant cytopenias. This study aimed to evaluate the characteristics, identify predictors, and assess the management and consequences of cytopenias in the pediatric kidney transplant population. This is a single-center retrospective analysis of 89 pediatric kidney transplant recipients. Possible factors preceding cytopenias were compared with the goal of recognizing predictors for posttransplant cytopenias. Posttransplant neutropenias were analyzed for the total study period and separately for the period beyond 6months posttransplant (late neutropenias), to rule out confounding influences of induction and initial intensive therapy. Sixty patients (67%) developed at least one episode of posttransplant cytopenia. All episodes of posttransplant thrombocytopenias were mild or moderate. Posttransplant infections and graft rejection were found to be significant predictors for thrombocytopenia (HR 6.06, 95% CI 1.6-22.9, and HR 5.82, 95% CI 1.27-26.6, respectively). A total of 30% of posttransplant neutropenias were severe (ANC ≤ 500). Pretransplant dialysis and posttransplant infections were significant predictors for late neutropenias (HR 11.2, 95% CI 1.45-86.4, and HR 3.32, 95% CI 1.46-7.57, respectively). Graft rejection occurred in 10% of patients with cytopenia, all following neutropenia, within 3months from cytopenia appearance. In all such cases, mycophenolate mofetil dosing had been held or reduced prior to rejection. Posttransplant infections are substantial contributors to developing posttransplant cytopenias. Preemptive transplantation appears to reduce risk of late neutropenia, the accompanying reduction in immunosuppressive therapy, and the ensuing risk of graft rejection. An alternative response to neutropenia, possibly using granulocyte colony stimulating factor, may diminish graft rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Temporal validation of the Australian estimated post-transplant survival score.

The Australian estimated post-transplant survival (EPTS-AU) prediction score was developed by re-fitting the United States of America EPTS, without diabetes, to the Australian and New Zealand kidney transplant population over 2002-2013. The EPTS-AU score incorporates age, previous transplantation and time on dialysis. Diabetes was excluded from the score, as this was not previously recorded in the Australian allocation system. In May 2021, the EPTS-AU prediction score was incorporated into the Australian kidney allocation algorithm to optimize utility for recipients (maximized benefit). We aimed to temporally validate the EPTS-AU prediction score to ensure it can be used for this purpose. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of deceased donor kidney-only transplants between 2014 and 2021. We constructed Cox models for patient survival. We assessed validation using measures of model fit (Akaike information criterion and misspecification), discrimination (Harrell's C statistic and Kaplan-Meier curves), and calibration (observed vs. predicted survival). Six thousand four hundred and two recipients were included in the analysis. The EPTS-AU had moderate discrimination with a C statistic of 0.69 (95% CI 0.67, 0.71), and clear delineation between Kaplan-Meier's survival curves of EPTS-AU. The EPTS was well calibrated with the predicted survivals equating with the observed survival outcomes for all prognostic groups. The EPTS-AU performs reasonably well in choosing between recipients (discrimination) and to predict a recipient's survival (calibration). Reassuringly, the score is functioning as intended to predict post-transplant survival for recipients as part of the national allocation algorithm.

Frailty and Age-Associated Assessments Associated with Chronic Kidney Disease and Transplantation Outcomes.

Frailty is often defined as a decrease in physiological reserve and has been shown to be correlated with adverse health outcomes and mortality in the general population. This condition is highly prevalent in the chronic kidney disease (CKD) patient population as well as in kidney transplant (KT) recipients. Other age-associated changes include sarcopenia, nutrition, cognition, and depression. In assessing the contributions of these components to patient outcomes and their prevalence in the CKD and KT patient population, it can be determined how such variables may be associated with frailty and the extent to which they may impact the adverse outcomes an individual may experience. We sought to perform a systematic literature review to review published data on frailty and associated age-associated syndromes in CKD and KT patients. Over 80 references pertinent to frailty, sarcopenia, nutrition, cognition, or depression in patients with CKD or KT were identified. Systematic review was performed to evaluate the data supporting the use of the following approaches: Fried Frailty, Short Physical Performance Battery, Frailty Index, Sarcopenia Index, CT scan quantification of muscle mass, health-related quality of life, and assessment tools for nutrition, cognition, and depression. This report represents a comprehensive review of previously published research articles on this topic. The intersectionality between all these components in contributing to the patient's clinical status suggests a need for a multifaceted approach to developing comprehensive care and treatment for the CKD and KT population to improve outcomes before and after transplantation.

MyKidneyCoach, Patient Activation, and Clinical Outcomes in Diverse Kidney Transplant Recipients: A Randomized Control Pilot Trial.

This was a randomized, age-stratified, parallel-group, attention-control, pilot study in post-KT patients. Participants were randomized into the attention-control with access to MyKidneyCoach for education and self-management (n = 9) or the intervention with additional tailored nurse coaching (n = 7). Feasibility, acceptability, and clinical outcomes were assessed. The acceptability of MyKidneyCoach by System Usability Scale was 67.5 (95% confidence interval [CI], 59.1-75.9). Completion rates based on actively using MyKidneyCoach were 81% (95% CI, 57%-93%) and study retention rate of 73%. Patient activation measure significantly increased overall by a mean of 11 points (95% CI, 3.2-18.8). Additionally, Black patients (n = 7) had higher nutrition self-efficacy scores of 80.5 (95% CI, 74.4-86.7) compared with 75.6 (95% CI, 71.1-80.1) in non-Black patients (n = 9) but lower patient activation measure scores of 69.3 (95% CI, 56.3-82.3) compared with 71.8 (95% CI, 62.5-81) in non-Black patients after 3 mo. MyKidneyCoach was easy to use and readily accepted with low attrition, and improvements were demonstrated in patient-reported outcomes. Both Black and non-Black participants using MyKidneyCoach showed improvement in self-management competencies; thus, this intervention may help reduce healthcare inequities in KT.

Donor specific antibody surveillance among pediatric kidney transplant programs: A report from the improving renal outcome collaborative.

Kidney transplantation (KT) is the preferred treatment for children with end-stage kidney disease. Recent advances in immunosuppression and advances in donor specific antibody (DSA) testing have resulted in prolonged allograft survival; however, standardized approaches for surveillance DSA monitoring and management of de novo (dn) DSA are widely variable among pediatric KT programs. Pediatric transplant nephrologists in the multi-center Improving Renal Outcomes Collaborative (IROC) participated in a voluntary, web-based survey between 2019 and 2020. Centers provided information pertaining to frequency and timing of routine DSA surveillance and theoretical management of dnDSA development in the setting of stable graft function. 29/30 IROC centers responded to the survey. Among the participating centers, screening for DSA occurs, on average, every 3 months for the first 12months post-transplant. Antibody mean fluorescent intensity and trend most frequently directed changes in patient management. Increased creatinine above baseline was reported by all centers as an indication for DSA assessment outside of routine surveillance testing. 24/29 centers would continue to monitor DSA and/or intensify immunosuppression after detection of antibodies in the setting of stable graft function. In addition to enhanced monitoring, 10/29 centers reported performing an allograft biopsy upon detection of dnDSA, even in the setting of stable graft function. This descriptive report is the largest reported survey of pediatric transplant nephrologist practice patterns on this topic and provides a reference for monitoring dnDSA in the pediatric kidney transplant population.

The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications

Immunosuppressive drugs are widely used to prevent rejection after kidney transplantation. However, the pharmacological response to a given immunosuppressant can vary markedly between individuals, with some showing poor treatment responses and/or experiencing serious side effects. There is an unmet need for diagnostic tools that allow clinicians to individually tailor immunosuppressive therapy to a patient's immunological profile. The Immunobiogram (IMBG) is a novel blood-based in vitro diagnostic test that provides a pharmacodynamic readout of the immune response of individual patients to a range of immunosuppressants commonly used in kidney transplant recipients. Here, we discuss the current approaches used to measure the pharmacodynamic responses of individual patients to specific immunosuppressive drugs in vitro, which can then be correlated with patient's clinical outcomes. We also describe the procedure of the IMBG assay, and summarize the results obtained using the IMBG in different kidney transplant populations. Finally, we outline future directions and other novel applications of the IMBG, both in kidney transplant patients and other autoimmune diseases.

Tumors after kidney transplantation: a population study

One of the main causes of post-transplant-associated morbidity and mortality is cancer. The aims of the project were to study the neoplastic risk within the kidney transplant population and identify the determinants of this risk. A cohort of 462 renal transplant patients from 2010 to 2020 was considered. The expected incidence rates of post-transplant cancer development in the referenced population, the standardized incidence ratios (SIR) taking the Italian population as a comparison, and the absolute risk and the attributable fraction were extrapolated from these cohorts of patients. Kidney transplant recipients had an overall cancer risk of approximately three times that of the local population (SIR 2.8). A significantly increased number of cases were observed for Kaposi’s sarcoma (KS) (SIR 195) and hematological cancers (SIR 6.8). In the first 3 years post-transplant, the risk to develop either KS or hematological cancers was four times higher than in the following years; in all cases of KS, the diagnosis was within 2 years from the transplant. Post-transplant immunosuppression represents the cause of 99% of cases of KS and 85% of cases of lymphomas, while only 39% is represented by solid tumors. Data related to the incidence, the percentages attributable to post-transplant immunosuppression, and the time of onset of neoplasms, particularly for KS and hematological tumors could help improve the management for the follow-up in these patients.

Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits.

Increasing evidence indicates that exercise has beneficial effects on chronic inflammation, cardiorespiratory function, muscle and bone strength and metabolic markers in adults with chronic kidney disease (CKD), kidney failure or kidney transplants. However, the mechanisms that underlie these benefits have received little attention, and the available clinical evidence is mainly from small, short-duration (<12 weeks) exercise intervention studies. The available data, mainly from patients with CKD or on dialysis, suggest that exercise-mediated shifts towards a less inflammatory immune cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue may underlie improvements in inflammatory biomarkers. Exercise-mediated increases in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise stimulates an anabolic response in skeletal muscle in CKD, but increases in mitochondrial mass and satellite cell activation seem to be impaired in this population. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation and improvements in the levels of the bone-derived hormones klotho and fibroblast growth factor 23 (FGF23). Longer duration studies with larger sample sizes are needed to confirm these mechanisms in CKD, kidney failure and kidney transplant populations and provide evidence for targeted exercise interventions.