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BackgroundSphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5'phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects.ResultsOverall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes.ConclusionOur results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

INTRODUCTION: Living kidney donor evaluation is a lengthy and complex process requiring in-person visits. Access to transplant centers, travel costs, lost wages, and dependent care arrangements are barriers to willing donors initiating evaluation. Telemedicine can help streamline and epedite the evaluation process. We aimed to deeply understand donor experiences and preferences using hybrid telemedicine video/in-person visits to ease access to donor evaluation or counseling. METHODS: We conducted in-depth, semistructured interviews with donors or donor candidates who completed their evaluation through telemedicine/in-person, or in-person only visits at a tertiary transplant center between November 27, 2019 and March 1, 2021. Enrollment continued until data saturation was reached (interviews with 20 participants) when no new information emerged from additional interviews. Transcripts were analyzed using inductive thematic analysis. RESULTS: Eight themes were identified as follows: (i) reducing financial and logistical burdens (minimizing travel time and travel-related expenses), (ii) enhancing flexibility with scheduling (less time off work and child or family caregiver arrangements), (iii) importance of a walkthrough and establishing shared understanding, (iv) supporting information with technology and visual aids, (v) key role of the coordinator, (vi) preferred visit by provider role (meeting donor surgeon in-person to create rapport and engaging primary care provider in donor evaluation/follow-up), (vii) comparing modality differences in human connection, and (viii) opportunity for family and support network engagement (allowing loved ones to be involved in telemedicine visits irrespective of geographic locations and pandemic restrictions). CONCLUSION: Telemedicine/in-person hybrid model can make donor evaluation more accessible and convenient. Our findings help inform about determinants that influence the adoption of telemedicine to initiate donor evaluation to motivate willing donors. In addition, our results call for policy and legislation that support telemedicine services for living donor kidney transplantation across states.

The kidney is the most common solid organ transplant globally and rates continue to climb, driven by the increasing prevalence of end stage renal disease (ESRD). Compounded by advancements in surgical techniques and immunosuppression leading to longer graft survival, radiologists evermore commonly evaluate kidney transplant patients and candidates, underscoring their role along the transplant process. Multiphase computed tomography (CT) with multiplanar and 3D reformatting is the primary method for evaluating renal donor candidates, detailing renal size, vascular/collecting system anatomy, and identifying significant pathologies such as renal vascular diseases and nephrolithiasis. Ultrasound is the preferred initial postoperative imaging modality for graft evaluation due to its low cost, accessibility, noninvasiveness, and lack of radiation. CT and magnetic resonance imaging (MRI) may be useful adjunctive imaging techniques in diagnosing transplant pathology when ultrasound alone is not diagnostic. Kidney transplant complications are categorized by an approximate timeline framework, aiding in differential diagnosis based on onset, duration, and severity and include perinephric fluid collections, graft compression, iatrogenic injuries, vascular compromise, graft rejection, and neoplastic processes. This review discusses imaging strategies and important findings along the transplant timeline, from donor assessment to long-term recipient complications.

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

PURPOSE OF REVIEW: Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net. RECENT FINDINGS: The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys. Access to kidney transplantation following liver transplant alone (LTA) increased with favorable outcomes. Estimating GFR in liver transplant candidates remains challenging, and innovative methods are needed. SLK provided superior patient and graft survival compared to LTA only for patients with advanced CKD and dialysis at least 3 months. SLK can provide immunological protection against kidney rejection in highly sensitized candidates. Post-SLK transplant care is complex, with an increased risk of complications and hospitalization. SUMMARY: The SLK policy improved kidney access and utilization. Transplant centers are encouraged, under the safety net, to reserve SLK for liver transplant candidates with advanced CKD or dialysis at least 3 months while allowing lower thresholds for highly sensitized patients. Herein, we propose a practical approach to liver transplant candidates with kidney dysfunction.

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.

BACKGROUND: Residence in rural areas is often a barrier to health care access. To date, differences in access to kidney transplantation among children who reside in rural and micropolitan areas of the US have not been explored. METHODS: A retrospective cohort study of children

Managing patients with kidney allografts largely depends on biopsy diagnosis which is based on semiquantitative assessments of rejection features and extent of acute and chronic changes within the renal parenchyma. Current methods lack reproducibility while digital image data-driven computational models enable comprehensive and quantitative assays. In this study we aimed to develop a computational method for automated assessment of histopathology transformations within the tubulointerstitial compartment of the renal cortex. Whole slide images of modified Picrosirius red-stained biopsy slides were used for the training (n = 852) and both internal (n = 172) and external (n = 94) tests datasets. The pipeline utilizes deep learning segmentations of renal tubules, interstitium, and peritubular capillaries from which morphometry features were extracted. Seven indicators were selected for exploring the intrinsic spatial interactions within the tubulointerstitial compartment. A principal component analysis revealed two independent factors which can be interpreted as representing chronic and acute tubulointerstitial injury. A K-means clustering classified biopsies according to potential phenotypes of combined acute and chronic transformations of various degrees. We conclude that multivariate analyses of tubulointerstitial morphometry transformations enable extraction of and quantification of acute and chronic components of injury. The method is developed for renal allograft biopsies; however, the principle can be applied more broadly for kidney pathology assessment.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

BackgroundRemote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation.MethodsA comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor).ResultsOur meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P

OBJECTIVE: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The studys objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. METHODS: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. RESULTS: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR:

The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary nonfunction in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0-6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10 years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool. [ABSTRACT FROM AUTHOR]

Aims: Tacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug–drug interactions (DDI). Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid–tacrolimus DDI differs by CYP3A4/5 genotypes. Methods: Kidney transplant recipients (n = 2462) were classified by the number of loss of function alleles (LOF) (CYP3A5*3, *6 and *7 and CYP3A4*22) and steroid use at each tacrolimus trough in the first 6 months post‐transplant. A population pharmacokinetic analysis was performed by nonlinear mixed‐effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R. Results: Steroids were associated with modestly higher (3%–11.8%) tacrolimus clearance. Patients with 0‐LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2‐LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1‐LOF and 3/4‐LOFs, respectively. Conclusions: Steroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses. [ABSTRACT FROM AUTHOR]

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on a recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) which uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforces, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, resource-sensitive manners. Policies to increase use of public funding for kidney care, lower the cost of KRT and increase workforces should be a high priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure (BP) modalities in kidney transplant recipients (KTRs). Methods For this prospective cross-sectional study, 89 stable KTRs were recruited at the Charité Transplant Outpatient Clinic. For each study participant office [manual office BP (MOBP) and automated office BP (AOBP)], 7-day home (HBPM) and 24-hour ambulatory BP (24h-ABPM) measurements were performed. Results 80 of the 89 patients recruited had sufficient BP recordings. The mean BP for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81 mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean ≥130/80 mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients, respectively, as 'uncontrolled hypertensive'. The Bland–Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and daytime-ABPM (mean bias: −1 ± 13 mmHg, −4 ± 13 mmHg, 1 ± 10 mmHg, respectively). Uncontrolled night-time hypertension was present in 74 (93%) KTRs, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between daytime-ABPM/HBPM and night-time-ABPM (Pearson correlation coefficients: 0.62–0.73), followed by MOBP/AOBP (Pearson correlation coefficients: 0.49–0.59) was noted. Estimated eGFR and proteinuria displayed weak correlation with 24h-, daytime- and night-time-ABPM (absolute values of Pearson correlation coefficients: 0.04–0.41). No robust association with either 24h-, daytime- or night-time-ABPM was observed for volume status exams. Conclusions Masked hypertension is highly prevalent in KTRs, especially due to high rates of uncontrolled night-time hypertension. HBPM shows the narrowest limits of agreement with daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with night-time-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the 2023 ESH guidelines for the management of arterial hypertension, should not be withheld for the KTR population. Clinical trials evaluating the treatment of hypertension in KTRs are urgently needed. [ABSTRACT FROM AUTHOR]

Background In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe. Methods Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017–2019. Changes occurring during the first and second waves of the pandemic were also explored. Results The incidence of KRT was 6.2% lower in 2020 compared with 2017–2019, with the lowest point (−22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (−5.2%) than in females (−8.2%) and was moderate for peritoneal dialysis (−3.7%) and haemodialysis (−5.4%) but substantial for pre-emptive kidney transplantation (−23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of −80.1% during the first wave, and was greatest for living donor kidney transplants (−30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65–74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N  = 317 787) resembled that of 2019 (N  = 317 077). Conclusion The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is the best treatment for end‐stage kidney disease but requires immunosuppressive medications, which have significant side effects. Many pediatric recipients experience these side effects, leading to dosage reductions, which potentially increase the risk of alloimmunity. We aimed to describe the alteration in immunosuppressive medication, explore the reasons for the reductions, and assess the potential impact on alloimmunity. Method: Data from 49 pediatric kidney transplant recipients receiving an allograft from 2009 to 2020 were retrospectively studied. The recipients were screened for HLA antibodies after the transplantation. Results: The median age of recipients was 11 years (IQR 8), with a median follow‐up of 5 years (IQR 5). Eighty percent of the transplantations were corticosteroid‐free. During follow‐up, 11% developed de novo donor‐specific antibodies (dnDSA), and 60% had detectable HLA antibodies. The 1‐year rejection rate was 4%. Immunosuppressive medication was altered substantially in most recipients, resulting in 72% being on mono‐ or dual therapy with a reduced mycophenolate mofetil (MMF) dosage by the end of the first posttransplant year. The median MMF dose was nearly half of the intended. Tacrolimus levels were maintained close to the target of 5 ng/mL. No association was found between reduced immunosuppression and dnDSA or rejections. Reductions were primarily due to MMF‐related side effects: leukopenia in 77%, gastrointestinal issues in 34%, and infections with Epstein–Barr virus, cytomegalovirus, and BK polyomavirus in 49%. Conclusions: Reduced MMF with a sufficient trough tacrolimus level in a population of mainly corticosteroid‐free pediatric kidney transplant recipients did not lead to unacceptable alloimmunity. [ABSTRACT FROM AUTHOR]

Kidney transplantation in children with end‐stage kidney disease significantly enhances survival and quality of life but poses unique challenges related to chronic immunosuppressive therapy. In fact, despite being essential for preventing organ rejection, immunosuppressive therapy can have significant side effects specific to pediatric patients, such as adverse impacts on physiological growth, puberty, and fertility. The resulting short stature and delayed or incomplete pubertal development can profoundly affect young patients' psychological and social well‐being, impacting self‐esteem and overall quality of life, and may significantly hamper compliance and therapeutic adherence. Most studies on immunosuppression in pediatric kidney transplant recipients focus on general side effects and outcomes like long‐term graft survival or acute complications. On the other side, there is limited evidence in the current literature on the specific issues of growth, puberty, and fertility in this patient population. In this pragmatic review, we aimed to summarize the most relevant information available on these critical aspects of post‐transplant management in pediatric patients, also providing some practical indications on management strategies for minimizing these often neglected but still important complications. [ABSTRACT FROM AUTHOR]

Due to the current organ shortage waitlist, alternatives to allotransplantation are necessary. Xenotransplantation is currently being pursued as one such alternative in adults in need of kidney or heart transplantation. Cardiac xenotransplantation of genetically modified pig hearts has been conducted twice in adults under the United States Food and Drug Administration (FDA) expanded access criteria. Because of the shortage of transplantable hearts for children as well as the lack of mechanical circulatory support in this population, pediatric researchers are exploring FDA expanded access in high‐risk neonates and infants who lack alternative options for survival. The adult cardiac xenotransplantation experience with expanded access can provide lessons and highlight nuances for researchers preparing pediatric application. This includes aspects of informed consent, biosurveillance, and protection of bystanders from potential xenozoonoses. [ABSTRACT FROM AUTHOR]

Background: Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post‐KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA). Methods: A retrospective cohort analysis of all first kidney transplant recipients between birth—24 years of age, from 2000 to 2019 in New Zealand. Participant identification and data were obtained via the Australia and New Zealand Dialysis and Transplantation registry. Primary outcome was graft survival stratified by service type. Cox proportional hazard modeling assessed independent risk factors of graft loss. Results: Two hundred forty‐four children and AYA with a median follow‐up of 7.3 years were included. Graft survival stratified by service provision group was not different. The incidence rate of graft loss was 37, 34, and 45 per 1000 persons per year for PO, PTA, and AO respectively. Crude age‐specific graft failure rates were highest for 22–24‐year‐olds with inferior outcomes starting from age 16, peaking at 24 years. Conclusions: Older adolescence and young adulthood reflect a high‐risk period for KT loss. Transfer to adult services was not associated with worse graft survival compared to those experiencing either AO or PO alone. Improved models of care are needed to improve graft survival in this vulnerable population within New Zealand. [ABSTRACT FROM AUTHOR]

Background: Encapsulating peritoneal sclerosis (EPS) is an uncommon complication of long‐term peritoneal dialysis (PD). Despite its rarity, EPS significantly increases morbidity and mortality in patients undergoing prolonged peritoneal dialysis. In children on PD, the incidence of EPS ranges from 0.5% to 7.3%. Case: We present the case of a 13‐year‐old Omani boy diagnosed with end‐stage kidney disease (ESKD) secondary to steroid‐resistant nephrotic syndrome due to diffuse mesangial sclerosis at the age of 2 years. He was started on automated peritoneal dialysis (APD) on the same year and experienced four episodes of peritonitis, which were treated successfully with intraperitoneal (IP) antibiotics. In January 2023, he developed intermittent abdominal pain and chronic constipation, which progressed to daily vomiting, reduced oral intake, and weight loss. He later developed subacute intestinal obstruction which was managed conservatively. A CT scan of the abdomen revealed findings consistent with EPS. Following the diagnosis of EPS, peritoneal dialysis (PD) was discontinued, and the patient transitioned to hemodialysis. Treatment for EPS began with steroids and Tamoxifen. Subsequently, he underwent deceased donor kidney transplantation and was started on multiple immunosuppressive medications. During subsequent follow‐up appointments, he was maintained on total parenteral nutrition (TPN) along with a soft diet. His overall condition improved significantly, enhancing his quality of life. Conclusion: This case highlights the risk of encapsulating peritoneal sclerosis (EPS) in patients undergoing long‐term peritoneal dialysis. Transitioning to hemodialysis and kidney transplantation, combined with targeted treatments such as steroids and Tamoxifen, significantly improved the patient's condition and quality of life. Early diagnosis and intervention are crucial for effective management of EPS in children. [ABSTRACT FROM AUTHOR]

Background: Learning Health Networks (LHN) have evolved within medicine over the past two decades, but their integration into transplantation has been more recent. Objectives and Methods: In this paper, we describe three LHNs in end‐stage organ disease/transplantation, their common and unique features, and how their "actor‐oriented" architecture allowed for rapid adaptation to meet the needs of their patients and practitioners during the recent COVID‐19 pandemic. Result: The structure and focus of the Improving Renal Outcomes Collaborative (IROC), Starzl Network for Excellence in Pediatric Transplantation (SNEPT), and the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) are reviewed. We discuss the critical role of patient and family engagement, focusing on collaboration with Transplant Families. Finally, we review challenges common to the LHN concept and potential common areas of alignment to achieve the goal of more rapid and sustained progress to improve health in pediatric transplantation. Conclusion: LHN in transplantation are essential to accelerate knowledge dissemination and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Life with end‐stage organ failure is accompanied by an accumulation of traumatic medical or surgical experiences. Despite recovery after solid organ transplantation (SOT), many children and adolescents develop post‐traumatic stress symptoms (PTSS). PTSS remain underappreciated as a major comorbidity in SOT programs, despite their association with decreased quality of life. Methods: We conducted a retrospective, cross‐sectional study of 86 pediatric SOT recipients (17 heart, 44 kidney, and 25 liver) to evaluate potential determinants of PTSS. Trauma symptoms were measured by the Child Trauma Screening Questionnaire (CTSQ). Demographic, baseline, and contemporaneous factors were tested for independent association with CTSQ scores. Results: The median post‐transplant CTSQ score was 2 (IQR 1–4), and 22% were identified as high risk (score ≥5) for PTSD. Higher CTSQ scores were independently associated with the number of ICU days within the previous 12 months, the number of medications (complexity), and involvement with foster care in the primary model (R2 [adj.] = 0.26). The addition of the Family Impact Module improved the overall model (R2 [adj.] = 0.33), wherein higher family functioning was independently associated with lower CTSQ scores. An exploratory analysis of pre‐transplant patients (n = 34) found a median pre‐transplant CTSQ of 2 (IQR 1–6), suggesting that PTSS are onset before transplant and persist afterward. Conclusions: PTSS are highly prevalent in the SOT population. Risk factors include recent adverse medical experiences and complexity, whereas family stability may be protective. Additional research is needed to improve early ascertainment and support for patients at high risk of developing PTSS throughout their transplant journey. [ABSTRACT FROM AUTHOR]

Background: The survival of pediatric chronic kidney disease (CKD) patients has improved in recent decades due to advances in dialysis and transplantation. However, cardiovascular disease (CVD) emerges as the main cause of mortality in patients with CKD. Objectives: To estimate cardiovascular risk in children with CKD at least 1 year after kidney transplantation. In addition, the possible association of cardiovascular risk with classic biochemical markers and potential new markers of this outcome was investigated. Methods: An observational ambidirectional (retrospective capture of risk factors and prospective study of outcomes) research including 75 patients who underwent renal transplant between 2003 and 2013 with postoperative follow‐up of at least 1 year was conducted. The outcome variables adopted were the LV mass Z‐score and the presence of coronary calcification on computed tomography using calcium Agatston score. Result: Only one patient had an elevated calcium score, and three children (4%) had an LV mass Z‐score ≥ 2.0. After multivariable analysis, only gender, serum triglyceride, and serum renalase concentration remained significantly associated with LV mass. Conclusion: The low incidence of cardiovascular changes in the population studied confirms the benefit of transplantation for the cardiovascular health of children. Nevertheless, long‐term follow‐up of these patients is recommended, given the limited duration of kidney function provided by transplantation and the high likelihood of further dialysis and kidney transplants being required in these children. [ABSTRACT FROM AUTHOR]

Introduction: Diarrhea is a frequent complication after kidney transplantation, however the etiology is often not identified. Multiplex PCR assays may increase the detection of diarrheal pathogens among kidney transplant recipients (KTRs), leading to improved management. Methods: This was a retrospective before–after study, conducted in a high-volume transplant center. In September 2017, multiplex PCR assay was introduced. We reviewed all hospitalized KTRs with diarrhea during 1/2015–8/2017 (pre-GI PCR, n = 111) and 9/2017–12/2021 (GI PCR, n = 159) and followed them for 3 years. We performed univariate and multivariate analysis for predictors of pathogen identification, introducing the study period as an independent variable. Results: Among 270 hospitalized KTRs with diarrhea, 64 (24%) had an identified diarrheal pathogen. The proportion of KTRs with an identified pathogen increased from 20% (13/64) in the pre-GI PCR to 80% (51/64) post GI PCR (p < 0.01). Of 51 KTRs with an identified pathogen in the post GI PCR, 44 (86%) were diagnosed using GI PCR. GI PCR was more likely used in younger KTRs with more recent transplantation and higher creatinine level at admission. The most common non-C. difficile diarrheal pathogens in the post-GI PCR cohort were enteropathogenic Escherichia coli (n = 23, 58%), norovirus (n = 11, 28%), and Campylobacter (n = 11, 28%). Implementing GI PCR significantly increased the detection and identification of GI pathogens (odds ratio [OR] = 21, CI 95% 10–44; p < 0.001). Conclusions: Infectious etiologies of diarrhea were identified in a higher proportion of KTRs after the implementation of GI PCR. This emphasizes the importance of integrating this diagnostic tool into diarrhea workup in KTRs. [ABSTRACT FROM AUTHOR]

Background: Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. Methods: This 56‐year (1967–2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long‐term incidence of malignant cutaneous neoplasms in Mexican RTRs. Results: Over 56 years, 1642 RTRs (58% male) were studied. Median follow‐up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5–7.9), with an incidence density rate of 6.5 (95% CI: 5.4–7.9) per 1000 person‐years and a median latency of 9.8 years. Incidence increased with longer transplantation‐related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6–9.1) for any skin cancer and 7.5 (95% CI: 3.8–14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer‐related mortality rate of 2.7%. Limitations of the study include its single‐center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Conclusions: Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non‐White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs. [ABSTRACT FROM AUTHOR]

Improvement of long-term outcomes through targeted treatment is a primary concern in kidney transplant medicine. Currently, the validation of a rejection diagnosis and subsequent treatment depends on the histological assessment of allograft biopsy samples, according to the Banff classification system. However, the lack of (early) disease-specific tissue markers hinders accurate diagnosis and thus timely intervention. This challenge mainly results from an incomplete understanding of the pathophysiological processes underlying late allograft failure. Integration of large-scale multimodal approaches for investigating allograft biopsy samples might offer new insights into this pathophysiology, which are necessary for the identification of novel therapeutic targets and the development of tailored immunotherapeutic interventions. Several omics technologies — including transcriptomic, proteomic, lipidomic and metabolomic tools (and multimodal data analysis strategies) — can be applied to allograft biopsy investigation. However, despite their successful application in research settings and their potential clinical value, several barriers limit the broad implementation of many of these tools into clinical practice. Among spatial-omics technologies, mass spectrometry imaging, which is under-represented in the transplant field, has the potential to enable multi-omics investigations that might expand the insights gained with current clinical analysis technologies. Technological advances continue to enhance the clinical value of kidney biopsies. Here, the authors consider the potential of using spatial-omics in transplantation, including the use of mass spectrometry imaging, as graft monitoring and diagnostic tools, to improve patient management and outcomes. [ABSTRACT FROM AUTHOR]

Background: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects. Methods: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1 week, and 1 month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli, and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA). Results: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p < 0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p = 0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila (p = 0.12), Bacteroid fragilis (p = 0.75), Bifidobacterium (p = 0.99), Escherichia coli (p = 0.5), Faecalibacterium (p = 0.98), and Lactobacilli (p = 0.93) between patients with and without delayed graft function (DGF). Conclusion: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization. Methods: Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen. Results: Thirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were Ktr (1.48 h−1; 95% CI, 1.15–1.84), CL/F (16.0 L h−1; 95% CI, 10.3–20.4), Vc/F (24.9 L; 95% CI, 93.0–6.71E25), Vp/F (1590 L; 95% CI, 651–2994), and Q/F (36.2 L h−1; 95% CI, 9.63–74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme. Conclusion: We have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available. [ABSTRACT FROM AUTHOR]

Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with increased complications, rejection, and graft loss after kidney transplantation in adult and pediatric recipients. Elevated body mass index (BMI) is a common contraindication to transplant at adult kidney transplant programs; however, there is no data on such limitations for pediatric patients. Methods: Between October and December 2022, we conducted a survey of Pediatric Nephrology Research Consortium centers assessing the use of BMI in pediatric kidney transplant evaluation. Centers reporting utilization of BMI cutoffs were invited to submit patient-level data on children declined for active transplant listing due to BMI. Results: Thirty-nine centers responded to the survey (42% response rate); 51% include BMI in their written listing criteria, with a median BMI "cutoff" of 39 kg/m2 (range 30–50 kg/m2). Between January 1, 2016, and December 31, 2021, 30 children at 15 transplant centers were declined for listing status due to BMI. Patient-level data was provided for 19 children (63%) who were denied active listing status; median BMI was 42 kg/m2 (range 35.8–49.4 kg/m2) and 84% were on dialysis. One year after evaluation, seven patients (37%) had proceeded to active wait list status. Eight (42%) remained in inactive status and four (21%) were unlisted; ten of these 12 patients (83%) were on dialysis. Conclusions: The use of BMI in pediatric kidney transplant evaluation and listing varies among centers, but BMI limits access to transplant for some children. More information is needed on the outcomes of obese pediatric kidney candidates who are and are not transplanted, to guide development of national and international consensus. [ABSTRACT FROM AUTHOR]

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with kidney failure often experience cognitive delays. However, academic delay (being more than one grade level below age-appropriate grade, or in special education) after pediatric kidney transplantation (KTx) has not been explored. We sought to identify patient characteristics associated with a higher risk of academic delay 1 year post-KTx. Methods: We used the United Network for Organ Sharing (UNOS) database to identify children aged 6–17 years who received a primary KTx between 2014 and 2021 and had a functioning graft 1 year after KTx. The primary outcome was the patient's academic progress at 1 year post-transplant. The secondary outcome was change in academic progress between transplant and 1-year follow-up: onset of new delay, resolution of pre-existing delay, persistence of delay, or no delay at either timepoint. Binomial and multinomial mixed effects logistic regression models were used to predict each outcome based on patient characteristics. Results: The study included 2197 patients, of whom 14% demonstrated academic delay at 1 year post-KTx, 4% demonstrated a new onset of academic delay, 5% demonstrated a resolution of academic delay, and 10% demonstrated persistent academic delay. Patients undergoing transplantation at a younger age, receiving a deceased donor kidney, experiencing longer waitlist times, and undergoing KTx for vascular or other disease indications for KTx were more likely to experience academic delays, including new-onset academic delays. Conclusions: Academic delays are frequently reported among pediatric KTx recipients. Additional academic support may help resolving or preventing academic delay for at-risk subgroups of children undergoing KTx. [ABSTRACT FROM AUTHOR]

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy. [ABSTRACT FROM AUTHOR]

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment. [ABSTRACT FROM AUTHOR]

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Background: Pronase pretreatment can reduce rituximab (RTX) interference by degrading CD20 in B-cell flow cytometry crossmatch (FCXM) testing. However, it may also reduce the assay sensitivity by degrading HLA molecules. We investigated the effects of various pronase concentrations on RTX interference and the analytical sensitivity of B-cell FCXM testing. Methods: Using 59 patient serum samples and 38 donor lymphocyte samples, we designed 97 recipient–donor pairs and divided them into three groups according to RTX use and the presence of weak-to-moderate donor HLA-specific antibody (DSA) reactions: RTX+/DSA−, RTX+/DSA+, and RTX−/DSA+. FCXM was performed after pretreating lymphocytes with six different pronase concentrations (0, 0.5, 1, 2, 3, and 4 mg/mL). Results: With B-FCXM testing, false-positive results due to RTX in the RTX+/DSA– group markedly decreased with increasing pronase concentrations. The median channel shift values in the RTX+/DSA+ and RTX−/DSA+ groups did not significantly decrease when the pronase concentration was increased from 1 mg/mL to 2 or 3 mg/mL. All eight RTX+/DSA+ cases that were positive at 1 mg/mL pronase but negative at 2 or 3 mg/mL had mean fluorescence intensity (MFI) DSA values of less than 3,000 except for DQ5 (MFI: 5,226). With T-cell FCXM, false-positive results were observed in 2.9% of 315 FCXM tests with pronase pretreatment. Conclusions: Higher concentrations (2 or 3 mg/mL) of pronase effectively eliminated RTX interference but still carried a risk for false negativity for weak DSA reactions in B-cell FCXM. Higher pronase concentrations can be used as an auxiliary method to detect moderate-to-strong DSA reactions in RTX-treated patients. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation.AcceSS and Equity in Transplantation (ASSET), a health‐linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as ‘transplanting’, ‘intermediate’ or ‘remote’ depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web‐based mapping software was used to develop interactive geospatial maps.The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61–0.88)] or remote [OR: 0.38 (95% CI: 0.27–0.54)) region and Māori (OR: 0.35 (95% CI: 0.28–0.44)], Pacific [OR: 0.32 (95% CI: 0.24–0.42)) and Asian (OR: 0.66 (95% CI: 0.50–0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here.There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need. [ABSTRACT FROM AUTHOR]

Background: Denosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied. Results: The cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome. Conclusion: The model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data. [ABSTRACT FROM AUTHOR]

Introduction Methods Findings Conclusions The complexity of managing patients with end‐stage kidney disease on hemodialysis underscores the importance of implementing quality improvement (QI) initiatives to enhance patient safety and prioritize patient‐centered care. To address this, we established a QI committee at our tertiary academic center focusing on evidence‐based practices, patient‐centered approaches, and cost efficiency. To facilitate the seamless implementation of QI initiatives, we leveraged the capabilities of our electronic medical record (EMR) system.This review details effective strategies for optimizing use of an EMR system to successfully implement QI efforts. Drawing from our experience, we provide detailed descriptions and practical insights that can be applied to other EMRs.The creation of a secure and accessible dashboard, offering real‐time data on quality metrics, stands out as the most notable feature. This dashboard operates through an algorithm that merges data from both our dialysis and hospital EMR systems. Its primary objectives are to streamline the identification of high‐priority patients, enhance team communication, and facilitate tracking of quality indicators. Additionally, we integrated clinical pathways, checklists, and standardized protocols into the renal EMR to ensure smooth implementation of QI interventions. Notable examples of these interventions include an incremental hemodialysis protocol, a new hemodialysis start checklist, vaccination care plans, and personalized kidney transplant workups. Programmed electronic automatic reminders have proven invaluable in ensuring timely follow‐ups of assigned tasks. The EMR has also contributed to medication optimization and deprescribing by generating patient lists based on specific medication classes. Finally, the EMR's capability to swiftly generate lists of patients with specific features has significantly facilitated targeted QI interventions.Leveraging the capabilities of an EMR system can be crucial for enhancing care of hemodialysis patients and implementing effective QI initiatives. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Treatment strategies for BK polyomavirus (BKPyV) infection in kidney transplant recipients are heterogeneous among clinicians. We aimed to identify the treatment preferences of key stakeholders for BKPyV infection and measure the trade‐offs between treatment outcomes.Adult kidney transplant recipients, caregivers, and clinicians were eligible to participate in a discrete choice experiment between February 2021 and June 2022. The five treatment‐related attributes were achieving viral clearance and optimal graft function, as well as reducing the risk of graft loss, acute rejection, and complications. Results were analyzed using multinomial logistic models.In total, 109 participants (57 kidney transplant recipients, 10 caregivers, and 42 health professionals) were included. The most important attribute was the risk of graft loss, followed by side effects and acute rejection. As the risk of graft loss increased, all participants were less inclined to accept an assigned treatment strategy. For instance, if graft loss risk was increased from 1% to 50%, the probability of uptake of a treatment strategy for BKPyV infection was reduced from 87% to 3%.Graft loss is the predominant concern for patients, caregivers, and health professionals when deciding on the treatment for BKPyV infection, and should be included in intervention trials of BKPyV infection. [ABSTRACT FROM AUTHOR]

Letermovir (LET) is a novel antiviral agent recently approved for cytomegalovirus (CMV) prophylaxis of renal transplant patients in Japan. However, its interactions with tacrolimus (TAC), an important immunosuppressant, remain ambiguous, warranting careful evaluation considering the unique genetic and physiological characteristics of Japanese patients. Therefore, in this study, we aimed to investigate the drug-drug interactions between LET and extended-release TAC (ER-TAC) in Japanese renal transplant patients via physiologically based pharmacokinetic (PBPK) modeling. We developed PBPK models for LET and TAC, including a new model for ER-TAC, using the Simcyp simulator. We also created a virtual Japanese post-transplant population by incorporating physiological parameters specific to Japanese patients, including CYP3A5 genotypes. Our model accurately predicted the pharmacokinetics of both immediate-release and ER-TAC co-administered with LET. In the Japanese population, LET significantly increased ER-TAC exposure, with the effect varying by CYP3A5 genotype. For CYP3A5*1 carrier, the area under the curve ratio ranged from 2.33 to 2.53, while for CYP3A5*3/*3 carriers, it ranged from 2.82 to 2.86. The maximum concentration ratio was approximately 1.50 across all groups. Our findings suggest reducing the ER-TAC dose by approximately 57-60% for CYP3A5*1 carrier and 65% for CYP3A5*3/*3 carriers when co-administered with LET for Japanese renal transplant patients. Moreover, the developed model incorporating population-specific factors, such as hematocrit values and CYP3A5 genotype frequencies, is a valuable tool to evaluate complex drug interactions and guide the dosing strategies for LET and TAC in Japanese patients. Overall, this study expands the application of PBPK modeling in transplant pharmacology, contributing to the development of effective immunosuppressive strategies for Japanese renal transplant patients. [ABSTRACT FROM AUTHOR]

Background: Infusion of mesenchymal stromal cells (MSCs) has been proposed as immune-modulatory therapy in solid organ transplantation. The use of allogenic MSCs could improve standardization and allow for direct availability of the product. Method: The nonrandomized phase Ib Neptune clinical trial provided safety and feasibility data on the use of allogenic bone-marrow-derived MSCs, infused in 10 patients at week 25 and 26 post kidney transplantation. Here, we performed detailed analysis on the peripheral blood immune cell composition of these patients up to 52 weeks post transplantation. We used a 40 marker antibody panel with mass cytometry to assess potential effects of MSC therapy on the immune system. Results: We showed minor changes in major immune lineages at week 27, 34 and 52 post kidney transplantation after MSC infusion at week 25 and week 26, confirming previous data with regular flow cytometry. However, in a direct comparison between pre- and post MSC infusion, as soon as 4 hours after MSC infusion, we observed a significant increase in cell numbers of B cell and T cell subsets that shared a unique expression of CD11b, CD11c, CD38, CD39, and Ki-67. Conclusion: Exploring these CD11b+CD11c+CD38+CD39+Ki-67+ B cells and T cells in the context of MSC infusion after kidney transplantation may be a promising avenue to better understand the immunological effects of MSC therapy. [ABSTRACT FROM AUTHOR]

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals. Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure. Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors. Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics. [ABSTRACT FROM AUTHOR]

BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research Only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95 % confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval ICI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 9596) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 9096) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21°/0) and 3 years (21% vs. 2496). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95°/0, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.). [ABSTRACT FROM AUTHOR]

Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+ circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination. [ABSTRACT FROM AUTHOR]

The KATITA-25 (Kidney AlloTransplant Immunosuppressive Therapy Adherence) Questionnaire is a multidimensional self-administered scale developed in Brazilian Portuguese that measures the predisposition for non-adherence to immunosuppressive medication in candidate patients for kidney transplantation, in the pre-transplant setting. The aim of this study was the cross-cultural validation of the Spanish version of the KATITA-25 scale. The translation/back-translation method was used, followed by cognitive interviews and a pre-test. The Spanish version of KATITA-25 was administered to 163 candidate patients for kidney transplantation from 2 kidney transplant centres and 2 dialysis centres in Catalonia, Spain. The scale was re-administered to the first 79 patients included into the study, after a 2 to 4 weeks interval. Internal consistency was assessed using Cronbach's alpha, test–retest reliability with the intraclass correlation coefficient (ICC); construct validity with goodness of fit indices after confirmatory factor analysis using structural equation modelling. The Cronbach's alpha of the Spanish version was 0.83, the ICC was 0.86. Confirmatory factor analysis showed adequate fit of the structural model. Overall, the analytical results closely resembled those obtained in the validation of the original scale. In conclusion, this cross-cultural validation study showed adequate reliability and construct validity of the Spanish version of the KATITA-25 questionnaire. [ABSTRACT FROM AUTHOR]

This study aims to analyze data from patients who received kidney transplantation from deceased donors to investigate the anesthetic factors influencing early and late graft outcomes, including the incidence of slow graft function (SGF), delayed graft function (DGF), and 3-year graft outcomes. We retrospectively analyzed 202 recipients who underwent deceased donor kidney transplantation from March 2010 to December 2020. Anesthetic monitoring data during the intraoperative period was analyzed at 5-minute intervals, and basic clinical parameters were evaluated. The mean recipient age was 46.6 ± 10.3 years, and the mean donor age was 41.7 ± 12.7 years. Anesthetic time averaged 285.8 ± 70.2 min, and operation time averaged 223.1 ± 44.0 min. The incidence of SGF was 11.8%, and the incidence of DGF was 3.9%. Mean central venous pressures (CVPs) were higher in recipients with SGF or DGF (11.7 mmHg) compared to those with immediate graft function (9.7 mmHg). Higher CVP was identified as an independent risk factor for SGF or DGF (odds ratio 1.219, p = 0.006). This study suggests that intraoperative monitoring of CVP is crucial for predicting short-term graft function in deceased donor kidney transplantation and should be managed to prevent excessive fluid intake. [ABSTRACT FROM AUTHOR]

We describe a case of severe symptomatic tumoral calcinosis in a young man with end stage kidney disease secondary to antineutrophil cytoplasmic antibodies‐associated vasculitis with longstanding hyperphosphatemia and secondary hyperparathyroidism while on several years of peritoneal dialysis. The use of intravenous sodium thiosulfate, optimization of clearance with five times weekly hemodialysis, and intradialytic nutrition were used to treat his inoperable tumoral calcinosis. Over 3 months, he had a remarkable reduction in the size of his calcified masses and associated improvement in pain. He subsequently received a living donor kidney transplant. [ABSTRACT FROM AUTHOR]