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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:

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]

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]

Background: BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment. Case presentation: A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection. Conclusions: Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection. [ABSTRACT FROM AUTHOR]

Background: Perioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias. Objective: We aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant. Methods: This single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes. Results: Twenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05). Conclusion and Relevance: Both AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications. [ABSTRACT FROM AUTHOR]

The scarcity of organ donors relative to the number of patients with End Stage Kidney Disease (ESKD) has led to prolonged waiting times for kidney transplants, contributing to elevated cardiovascular mortality risk. Transplant professionals are tasked with the complex allocation of limited organs to a vulnerable patient group facing heightened morbidity and mortality risk. The need for continuous re-evaluation of waitlisted patients is evident due to the significant number who perish while awaiting transplantation. Among individuals with ESKD, vascular calcification, particularly Abdominal Arterial Calcifications (AAC), holds predictive value for cardiovascular events and mortality. However, a standardized method to quantify AAC's prognostic potential remains lacking, especially for kidney transplant evaluations. This study presents an ensemble machine learning (ML) approach to study the relationship between AAC score and mortality in patients on the waitlist and triage patients needing transplantation. Using the AAC score, the proposed ML model can predict kidney transplant waitlist morality with an accuracy of 78% while its accuracy is 68% without using this score. This study leverages explainable ML to explore the relationship between predictors and mortality in waitlisted patients, aiming to improve patient triage accuracy. [ABSTRACT FROM AUTHOR]

Kidney transplantation from donors with HIV to recipients with HIV (HIV D+/R+) is an emerging practice that has shown substantial clinical benefit. Sustained HIV superinfection, whereby a transplant recipient acquires a new strain of HIV from their organ donor, is a theoretical risk, which might increase chances of viral failure. In this issue of the JCI, Travieso, Stadtler, and colleagues present phylogenetic analysis of HIV from kidney tissue, urine, plasma, and cells from 12 HIV D+/R+ kidney transplants out to five years of follow-up. Early after transplant, donor HIV was transiently detected in five of 12 recipients, primarily from donors with untreated HIV and high-level viremia, consistent with a viral inoculum. Long-term, donor HIV was not detected in any recipients, demonstrating no sustained HIV superinfection. These reassuring data support earlier findings from South Africa and the United States and further confirm the safety of HIV D+/R+ transplantation. [ABSTRACT FROM AUTHOR]

Background Objective Design Participants Measurements Results Conclusion One of the most common problems encountered in transplant patients is nonadherence with immunosuppressive drugs, one of the most important reasons for graft rejection.The study aimed to assess the impact of text message reminders on medication adherence among kidney transplant recipients.A randomized controlled trial.The study was conducted from January to October 2021. This study included a total of 100 patients receiving a kidney transplant, 50 in the intervention group and 50 in the control group.Patients in the intervention group were sent text message reminders four times a day during the 6th–9th months after transplantation. Control patients received no such intervention. Tacrolimus concentrations in the bloodstream were monitored for all participants through measurements taken at Months 7, 8 and 9. Data collection tools included Sociodemographic Form and Immunosuppressive Medication Adherence Scale.Patients were homogeneously distributed among the groups. Sending daily text message reminders to transplant recipients caused an independent positive effect on medication adherence scale scores at the end of the study. Mean pretest medication adherence score of all patients was 45.18 ± 4.22 and posttest score was 47.4 ± 3.6. The intervention group exhibited a significantly higher mean posttest adherence score compared to controls, with values of 48.68 ± 2.58 and 45.62 ± 4.42, respectively (p < 0.001). Findings demonstrated a substantial improvement in the final medication adherence scores of transplant patients when they received daily Short Message Service reminders, acting as an independent factor (β = 0.356, p < 0.001).Sending text message reminders to kidney transplant recipients is a statistically and clinically effective intervention to improve immunosuppressive medication adherence. [ABSTRACT FROM AUTHOR]

The document explores the efforts of the Young Academic Urologists (YAU) group in the European Association of Urology to promote diversity, equity, and inclusion in academic urology. The YAU aims to foster a diverse community of future urology leaders by including members from various genders, countries, and cultural backgrounds. While progress has been made in increasing female representation, there is still work to be done to achieve gender balance in authorship and leadership roles. The YAU is actively working on defining and implementing criteria for diversity, equity, and inclusion within its working groups to enhance representation and opportunities for all members. The text underscores the importance of diversity, equity, and inclusion in urology, emphasizing the need for diverse representation in speaker rosters and the use of data analytical tools to measure progress. It also addresses challenges to DEI initiatives, such as lack of implementation, tracking, and discussion, as well as pressure for immediate results. The document stresses the necessity of a long-term vision for an inclusive future in the urological community and offers additional resources for those interested in further research on the topic. [Extracted from the article]

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101–153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1–3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15–22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106–159) µmol/L post-COVID-19 infection and 128 (101–161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection. [ABSTRACT FROM AUTHOR]

This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation stands as the optimal option, yet the scarcity of organs persists. Employing tissue engineering, researchers sought to assess the feasibility of generating kidneys for transplantation. Pig kidneys were utilized since they possess higher similarities to human kidneys. Cells were removed via decellularization, which maintains the organ's microarchitecture. Subsequently, pig kidney cells and human red blood cells were perfused into the vacant kidney structure to reconstitute it. The methodologies employed showed promising results, suggesting a viable approach to increase the recellularization rate in whole pig kidneys. This proof-of-concept establishes a groundwork for potentially extending this technology to human kidneys, tackling the organ shortage, thus positively enhancing outcomes for ESRD patients by increasing the availability of transplantable organs. [ABSTRACT FROM AUTHOR]

Background Aims The European Union encompasses 30 outermost and overseas countries and territories (OCTs). Despite a recent increasing activity of renal transplantation in these territories, many patients still undergo transplantation in continental Europe, with follow‐up care coordinated between health professionals from both their transplant center and their home region. Each territory has its unique infectious epidemiology which must be known to ensure appropriate care for kidney transplant recipients (KTRs).This paper proposes a pragmatic approach to optimize pre‐transplant check‐up and to provide an overview of the specific epidemiological features of each region. It offers practical algorithms to help practitioners in managing infected KTR living in these territories. This work advocates for increased collaborative research among European OCTs. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Development of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.This is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.A total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%.Brain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms. Case description: We present a case report of a 56-year-old patient with HAEC1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%. Conclusion: lanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy. [ABSTRACT FROM AUTHOR]

Introduction: Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss. Methods: To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies. Results: From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression. Discussion: NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP). [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Since the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV. Methods: Using linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events. Results: Overall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p = 0.9). Conclusion: By linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx. Summary: In a matched analysis based on longitudinal data from the Swiss HIV and Transplant Cohort Studies including all people with HIV who received a kidney transplantation, HIV was not an independent risk factor for infectious disease events post-transplant. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty.We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information.The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6–67.2) years and a median (IQR) age at transplantation of 58.6 (52.7–65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate‐specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5–10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow‐up of 5.8 (2.5–10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow‐up of 5.3 (1–8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer.A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. Methods: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. Results: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. Conclusions: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Optimal care for patients with kidney failure reduces the risks of adverse health outcomes, including cardiovascular events and death. We evaluated data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN‐GKHA) to assess the capacity for quality service delivery for kidney failure care across countries and regions.We explored the quality of kidney failure care delivery and the monitoring of quality indicators from data provided by an international survey of stakeholders from countries affiliated with the ISN from July to September 2022.One hundred and sixty seven countries participated in the survey, representing about 97.4% of the world's population. In countries where haemodialysis (HD) was available, 81% (n = 134) provided standard HD sessions (three times weekly for 3–4 h per session) to patients. Among countries with peritoneal dialysis (PD) services, 61% (n = 101) were able to provide standard PD care (3–4 exchanges per day). In high‐income countries, 98% (n = 62) reported that >75% of centers regularly monitored dialysis water quality for bacteria compared to 28% (n = 5) of low‐income countries (LICs). Capacity to monitor the administration of immunosuppression drugs was generally available in 21% (n = 4) of LICs, compared to 90% (n = 57) of high‐income countries. There was significant variability between and within regions and country income groups in reporting the quality of services utilized for kidney replacement therapies.Quality assurance standards on diagnostic and treatment tools were variable and particularly infrequent in LICs. Standardization of delivered care is essential for improving outcomes for people with kidney failure. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions We evaluated whether a history of low‐dose rituximab treatment affected herpes zoster development after living kidney transplantation.We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis.The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200–400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster‐free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events.Low‐dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMethodsResultsConclusionsThe effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored.To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population.This retrospective observational study utilising the COVID-19 Registry Japan (COVIREGI-JP) included noncritical patients with COVID-19 and severe renal insufficiency (defined as serum creatinine levels ≥3 mg/dL, on maintenance dialysis, or kidney transplant recipients) admitted to Japanese hospitals within 7 days of symptom onset between January 1, 2020 and May 8, 2023. Patients were classified into the remdesivir group if remdesivir was initiated within the first 2 days of admission. We estimated the multivariable-adjusted hazard ratio (HR) for mortality and initiation of IMV/ECMO using landmark analysis to address immortal time bias.Among the 1,449 patients included in the landmark analysis (median age, 74 years [interquartile range 62–84 years]; 992 [68.5%] were male), 272 initiated remdesivir within the first 2 days of admission. During the 28 days from the landmark timepoint, 19 (7.0%) and 136 (11.6%) patients in the remdesivir and control groups, respectively, had an outcome. The remdesivir group had a lower risk of mortality or IMV/ECMO initiation than the control group (adjusted HR, 0.44; 95% confidence interval, 0.23–0.83).In noncritical patients with COVID-19 and severe renal insufficiency at admission, initiating remdesivir early after disease onset, within the first 2 days of admission, led to a lower risk of mortality or IMV/ECMO initiation, compared with non-initiation of remdesivir. [ABSTRACT FROM AUTHOR]

Aims: The once-daily extended-release tacrolimus formulation (ER-Tac) has demonstrated similar efficacy and safety to the twice-daily immediate-release formulation (IR-Tac), but few population-based pharmacokinetic models have been developed in de novo kidney transplant patients to optimize doses. Therefore, this study aimed i) at developing a population pharmacokinetic model for ER-Tac in de novo adult kidney transplant patients ii) and identifying genetic factors and time-varying covariates predictive of pharmacokinetic variability to guide tacrolimus dosage during the early posttransplant period. Methods: A total of 1,067 blood tacrolimus concentrations from 138 kidney transplant patients were analyzed. A total of 29 out of 138 patients were intensively sampled for 24 h on the day 5 post-transplantation; meanwhile, for the remaining patients, concentrations were collected on days 5, 10, and 15 after transplantation. Tacrolimus daily doses and genetic and demographic characteristics were retrieved from the medical files. Biochemistry timevarying covariates were obtained on different days over the pharmacokinetic (PK) study. A simultaneous PK analysis of all concentrations was carried out using the non-linear mixed-effects approach with NONMEM 7.5. Results: A two-compartment model with linear elimination and delayed absorption best described the tacrolimus pharmacokinetics. Between-patient variability was associated with oral blood clearance (CL/F) and the central compartment distribution volume (Vc/F). Tacrolimus concentrations standardized to a hematocrit value of 45% significantly improved the model (p < 0.001). This method outperformed the standard covariate modeling of the hematocrit-blood clearance relationship. The effect of the CYP3A5 genotype was statistically (p < 0.001) and clinically significant on CL/F. The CL/F of patients who were CYP3A5*1 carriers was 51% higher than that of CYP3A5*1 non-carriers. Age also influenced CL/F variability (p < 0.001). Specifically, CL/F declined by 0.0562 units per each increased year from the value estimated in patients who were 60 years and younger. Conclusion: The 36% between-patient variability in CL/F was explained by CYP3A5 genotype, age, and hematocrit. Hematocrit standardization to 45% explained the variability of tacrolimus whole-blood concentrations, and this was of utmost importance in order to better interpret whole-blood tacrolimus concentrations during therapeutic drug monitoring. The dose requirements of CYP3A5*/1 carriers in patients aged 60 years or younger would be highest, while CYP3A5*/1 non-carriers older than 60 years would require the lowest doses. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion injury (IRI) is unavoidable during kidney transplant and it is responsible for delayed or non-function after kidney transplantation. Cysteamine is the standard drug in the management of nephropathic cystinosis and its extra-renal complications. Thus, we designed this study to investigate its potential against renal reperfusion injury. Results: Significant elevation of H2O2, MDA, and nitrite and reduced GPx, GSH, and protein thiol in the Ischemia-reperfusion injury rats was reversed by cysteamine (50 and 100 mg/kg). Serum MPO, TNF-a, IL-1ß, creatinine, and AOPP were significantly elevated in IRI while rats treated with cysteamine revealed a significant decrease (p < 0.05) in the activities of these proinflammatory and renal injury markers. Conclusion: Based on its activity against inflammation, apoptosis, and free radical-induced stress, cysteamine has great potential to be used as a kidney transplant pre-operative drug to prevent renal reperfusion injury. [ABSTRACT FROM AUTHOR]

Aim: Tacrolimus, an immunosuppressant used to prevent organ rejection in renal transplant patients, exhibits high inter-patient variability, necessitating therapeutic drug monitoring. Early post-transplant tacrolimus exposure in Hispanics is understudied. Although genotypic information is linked to pharmacokinetic differences, its clinical application remains limited. This study aimed to use a real-world data-driven, pharmacokinetic model-based approach for tacrolimus in Hispanics to determine a suitable initial dose and design an optimal dose titration strategy by simulations to achieve plasma trough concentration target levels of 10-12 ng/mL at the earliest. Methods: Sparse concentration-time data of tacrolimus were obtained from electronic medical records for self-identified Hispanic subjects following renal transplant. Rich pharmacokinetic literature data was leveraged to estimate structural pharmacokinetic model parameters, which were then fixed in the current analysis. Only apparent clearance was estimated with the sparse tacrolimus data and potential covariates were identified. Simulations of various starting doses and different dose titration strategies were then evaluated. Results: The analysis included 121 renal transplant patients with 2,215 trough tacrolimus concentrations. A two-compartment transit absorption model with allometrically scaled body weight and time-varying hematocrit on apparent clearance adequately described the data. The estimated apparent clearance was 13.7 L/h for a typical patientweighing 70 kg and at 30%hematocrit, demonstrating a 40% decrease in clearance compared to other patient populations. Model based simulations indicated the best initial dose for the Hispanic population is 0.1mg/kg/day. The proposed titration strategy, with three dose adjustments based on trough levels of tacrolimus, increased the proportion of patients within the target range (10-12 ng/mL) more than 2.5-fold and decreased the proportion of patients outside the therapeutic window by 50% after the first week of treatment. Conclusion: Hispanic renal transplant population showed an estimated 40% decrease of apparent clearance in the typical patient compared to other populations with similar characteristics. The proposed dose adjustment attained the target range rapidly and safely. This study advocates for tailored tacrolimus dosing regimens based on population pharmacokinetics to optimize therapy in Hispanic renal transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles. Methods: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2). Naive, memory, and regulatory peripheral blood TCD4+ lymphocytes were quantified at 0, 30, and 365 d. Results: Results are reported as [mean(p25--p75)]. Young recipients had higher lymphocyte counts at baseline [2,100(1,630--2,400) vs. 1,310 (1,000--1,600)/mm3, p<0.0001] maintained higher counts within 365 d [1,850(1,590--2,120) vs. 1,130 (460--1,325)/mm3, p=0.018 and vs. 1,410(805--1,895)/mm3, p=0.268]. Elderly recipients showed a decrease in lymphocytes within 30 d [1,310(1,000--1,600) vs. 910(700--1,198)/mm3, p=0.0012] with recovery within 365 d. The same pattern was observed in total lymphocytes and TCD4+ counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 d in both young recipients [6.2(3.77--10.8) vs. 5.32(2.49--7.28)% of CD4+, p=0.036] and in elderly recipients [8.17(5.28--12.88) vs. 6.74(4.36--11)% of CD4+, p=0.05] on standard immunosuppression, returning to baseline at 365 d in elderly recipients but not in young recipients. Regulatory T CD39+ cells (Treg) percentages decreased at 30 d in elderly recipients [2.1(1.23--3.51) vs. 1.69(0.8--2.66)% of CD4+, p=0.0028] and in young recipients [1.29(0.45--1.85) vs. 0.84(0.18--1.82)% of CD4+, p=0.0038], returning to baseline at 365 d in elderly recipients [2.1(1.23-- 3.51) vs. 2.042(0.88--2.42)% of CD4+], but not in young recipients [1.29(0.45--1.85) vs. 0.86(0.7--1.34) % of CD4+]. The elderly everolimus conversion group did not show significant changes in cell profile over time or compared to elderly recipients with standard immunosuppression. Conclusion: Aging favored the maintenance of Treg during the late transplantation period despite ongoing immunosuppression. Lymphocyte depletion due to rATG was more prominent in elderly recipients and affected memory subsets with a temporary reduction in central memory T cells. However, conversion to everolimus did not impact Treg profile. Reducing the dose of rATG in elderly recipients seems necessary for the expected lymphocyte changes with EVL to occur. Clinical trial registration: nEverOld Trial, identifier NTC01631058. [ABSTRACT FROM AUTHOR]

Background Access to kidney transplantation (KT) remains challenging for patients with end-stage kidney disease. This study assessed women's access to KT in France by considering comorbidities and neighbourhood social deprivation. Methods All incident patients 18–85 years old starting dialysis in France between 1 January 2017 and 31 December 2019 were included. Three outcomes were assessed: access to the KT waiting list after dialysis start, KT access after waitlisting and KT access after dialysis start. Cox and Fine–Gray models were used. Gender–European Deprivation Index and gender–age interactions were tested and analyses were performed among strata if required. Results A total of 29 395 patients were included (35% of women). After adjusting for social deprivation and comorbidities, women were less likely to be waitlisted at 1 year {adjusted hazard ratio [adjHR] 0.91 [95% confidence interval (CI) 0.87–0.96]} and 3 years [adjHR 0.87 (95% CI 0.84–0.91)] after dialysis initiation. This disparity concerned mainly women ≥60 years of age [adjHR 0.76 (95% CI 0.71–0.82) at 1 year and 0.75 (0.71–0.81) at 3 years]. Access to KT after 2 years of waitlisting was similar between genders. Access to KT was similar between genders at 3 years after dialysis start but decreased for women after 4 years [adjHR 0.93 (95% CI 0.88–0.99)] and longer [adjHR 0.90 (95% CI 0.85–0.96)] follow-up. Conclusions In France, women are less likely to be waitlisted and undergo KT. This is driven by the ≥60-year-old group and is not explained by comorbidities or social deprivation level. [ABSTRACT FROM AUTHOR]

Background The population with kidney failure is at increased risk of cancer and associated mortality. Relative survival can provide insight into the excess mortality, directly or indirectly, attributed to cancer in the population with kidney failure. Methods We estimated relative survival for people all ages receiving dialysis (n  = 4089) and kidney transplant recipients (n  = 3253) with de novo cancer, and for the general population with cancer in Australia and New Zealand (n  = 3 043 166) over the years 1980–2019. The entire general population was the reference group for background mortality, adjusted for sex, age, calendar year and country. We used Poisson regression to quantify excess mortality ratios. Results Five-year relative survival for all-site cancer was markedly lower than that for the general population for people receiving dialysis [0.25, 95% confidence interval (CI) 0.23–0.26] and kidney transplant recipients (0.55, 95% CI 0.53–0.57). In dialysis, excess mortality was more than double (2.16, 95% CI 2.08–2.25) that of the general population with cancer and for kidney transplant recipients 1.34 times higher (95% CI 1.27–2.41). There was no difference in excess mortality from lung cancer between people with kidney failure and the general population with cancer. Comparatively, there was a significant survival deficit for people with kidney failure, compared with the general population with cancer, for melanoma, breast cancer and prostate cancers. Conclusion Decreased cancer survival in kidney failure may reflect differences in multi-morbidity burden, reduced access to treatment, or greater harm from or reduced efficacy of treatments. Our findings support research aimed at investigating these hypotheses. [ABSTRACT FROM AUTHOR]

Background This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). Methods Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. Results In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13%, respectively), or underwent pre-emptive KTx (4%; 3%, respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). Conclusions The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft. [ABSTRACT FROM AUTHOR]

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = −0.250 and p = 0.04, citric acid with r = −0.296 and p = 0.014, formic acid with r = −0.349 and p = 0.004, and glycine with r = −0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the safety of a modified peritoneal fenestration technique with clipping of the window edges during kidney transplantation (KTx) and to determine its impact on reducing lymphocele following KTx. We compared the outcomes of this modified method with those of peritoneal fenestration without clipping. Methods: Among 430 consecutive KTxs performed between 2015 and 2019, preventive peritoneal fenestration and clipping of the margins were performed in 25 patients. These patients were compared with 75 matched patients in whom the margins were not clipped. Postoperative lymphocele formation and other patient data were compared between these two groups. Results: The rate of clinically relevant lymphocele decreased by 2.7% after peritoneal fenestration with clipping, although this decrease was not statistically significant (p = 0.829). There was no significant increase in the rate of other complications in the modified fenestration group (p = 0.067). The incidence of clinically significant lymphocele formation was notably higher in patients with a body mass index greater than 25 kg/m2 (p = 0.028). Univariate analysis indicated that older recipients, individuals with a history of previous abdominal surgery, those receiving the kidney from deceased and older donors were at increased risk of developing a clinically relevant lymphocele. Conclusions: Our preliminary results suggest that peritoneal fenestration with clipping may be as effective as the conventional fenestration technique in preventing lymphocele formation. Further clinical trials with larger sample sizes are required to determine the exact role of preventive peritoneal fenestration with clipping in preventing clinically relevant lymphocele after KTx. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population. Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD. Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years. Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population. [ABSTRACT FROM AUTHOR]

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts' survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure. [ABSTRACT FROM AUTHOR]

Introduction: Polyomavirus-associated nephropathy (BKPyVAN) is a common complication in kidney transplant recipients. The histological changes in the context of BKPyVAN and their association with the viral load and outcomes are still being investigated. Methods: This retrospective study involved 100 adult patients transplanted between 2000 and 2021, with available archived biopsy slides, aiming to analyze associations between viral load clearance in the blood (reduction in BKPyVAN-DNAemia below detection level) and histological features in biopsy-proven BKPyVAN. A kidney pathologist blinded to the clinical data reassessed the BANFF 2019 lesion scores in the BKPyVAN index biopsy. The primary endpoint was viral clearance three months after the diagnosis. Results: The presence of tubulointerstitial inflammation, peritubular capillaritis, and higher PVN Class at the diagnosis was linked to a reduced likelihood of viral clearance three months later (interstitial inflammation OR = 0.2, 95% CI [0.07–0.55], tubulitis OR = 0.39, 95% CI [0.21–0.73], peritubular capillaritis OR = 0.25, 95% CI [0.08–0.82], PVN Score OR = 0.1, 95% CI [0.03–0.4]), independently of other covariates. Combining the four lesions using the ROC analysis enhanced their capability to predict persistent BK viremia after 3 months with an AUC of 0.94. Conclusions: The presence of interstitial inflammation, tubulitis, and peritubular capillaritis, as well as the higher PVN Score, was associated with an up to 90% lower likelihood of viral load clearance three months post-diagnosis. These findings underscore the importance of histological evaluation as a surrogate of subsequent viral clearance and offer valuable insights for the management of BKPyVAN. [ABSTRACT FROM AUTHOR]

Background/Objectives: Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. Methods: 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. Results: CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. Conclusions: Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers. [ABSTRACT FROM AUTHOR]

(1) Background: Globally, the kidney donor shortage has made the allocation process critical for patients awaiting a kidney transplant. Adopting Machine Learning (ML) models for donor–recipient matching can potentially improve kidney allocation processes when compared with traditional points-based systems. (2) Methods: This study developed an ML-based approach for donor–recipient matching. A comprehensive evaluation was conducted using ten widely used classifiers (logistic regression, decision tree, random forest, support vector machine, gradient boosting, boost, CatBoost, LightGBM, naive Bayes, and neural networks) across three experimental scenarios to ensure a robust approach. The first scenario used the original dataset, the second used a merged version of the dataset, and the last scenario used a hierarchical architecture model. Additionally, a custom ranking algorithm was designed to identify the most suitable recipients. Finally, the ML-based donor–recipient matching model was integrated into a web-based platform called Nephron. (3) Results: The gradient boost model was the top performer, achieving a remarkable and consistent accuracy rate of 98% across the three experimental scenarios. Furthermore, the custom ranking algorithm outperformed the conventional cosine and Jaccard similarity methods in identifying the most suitable recipients. Importantly, the platform not only facilitated efficient patient selection and prioritisation for kidney allocation but can be flexibly adapted for other solid organ allocation systems built on similar criteria. (4) Conclusions: This study proposes an ML-based approach to optimize donor-recipient matching within the kidney allocation process. Successful implementation of this methodology demonstrates significant potential to enhance both efficiency and fairness in kidney transplantation. [ABSTRACT FROM AUTHOR]