Search

Background: Reactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population., Methods: This study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan's National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals., Results: This study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23-1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71-3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences., Conclusions: No significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Accelerated development of atherosclerosis has been observed in renal transplant recipients (RTRs). Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are vascular enzymes that play important roles in vascular development and angiogenesis., Objective: This study aimed to investigate the relationship between Ang-2 and VEGF and atherosclerosis in RTRs., Design and Setting: This study was conducted at Ankara City Hospital, Turkey., Methods: This cross-sectional study included 36 (37.5%) female and 60 (62.5%) male RTRs. All findings were compared with those of 70 healthy controls. Ultrasonographic measurements of the carotid artery intima-media thickness (CA-IMT) and renal resistive index (RRI) were used as indicators of atherosclerosis., Results: Log10 Ang-2, log10 VEGF, CA-IMT, and RRI levels were significantly higher in patients than in healthy controls. No significant differences were detected in CA-IMT and RRI between those with log10 Ang-2 ≥ 3.53 pg/mL and those with < 3.53 pg/mL. No significant differences were detected in CA-IMT and RRI between those with log10 VEGF ≥ 1.98 pg/mL and those with < 1.98 pg/mL. No correlation was detected between log10 Ang-2 and log10 VEGF, CA-IMT, or RRI., Conclusions: Increased serum angiogenic growth factor levels and increased atherosclerosis development were detected in RTRs compared to healthy individuals. No relationship was observed between angiogenic growth factors and atherosclerosis. This may be due to the decreased synthesis and effect of angiogenic growth factor receptors synthesized from atherosclerotic plaques due to atherosclerosis, which improves after renal transplantation.

Rejection seriously affects the success of kidney transplantations. However, the molecular mechanisms underlying this rejection remain unclear. The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to infer the proportions of 22 immune cells. Moreover, infiltrating immune cell-related genes were identified using weighted gene co-expression network analysis (WGCNA), and enrichment analysis was conducted to observe their biological functions. Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune cells and hub gene expression levels. The rejection and non-rejection groups showed significantly different distributions (P < 0.05) of eight immune cells (B cell memory, Plasma cells, mast cells, follicular helper T cells, T CD8 cells, Macrophages M1, T Cells CD4 memory activated, and gamma delta T cells). Subsequently, CD8A, CRTAM, GBP2, WARS, and VAMP5 were screened as hub genes using the XGBoost and LASSO algorithms and could be used as diagnostic biomarkers. Finally, differential analysis and quantitative real-time PCR suggested that CD8A, CRTAM, GBP2, WARS, and VAMP5 were upregulated in rejection samples compared to non-rejection samples. The present study identified five key infiltrating immune cell-related genes (CD8A, CRTAM, GBP2,WARS, and VAMP5) involved in kidney transplant rejection, which may explain the molecular mechanism of rejection in kidney transplantation development., (© 2024. The Author(s).)

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024. The Author(s).)

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 a 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 [CI], 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. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). 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%, 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.)., (Copyright © 2024 Massachusetts Medical Society.)

BACKGROUND Rejection is the main cause of kidney allograft failure, and kidney biopsy is the criterion standard method to diagnose it. However, non-invasive techniques to detect kidney transplant rejection are necessary. This study aimed to evaluate urinary chemokines CXCL9 and CXCL10 as potential biomarkers of kidney transplant rejection and to analyze chemokine association with allograft prognosis. MATERIAL AND METHODS We collected 117 urine samples from kidney transplant recipients undergoing allograft biopsy. CXCL9 and CXCL10 levels were measured by ELISA and the ratio to urine creatinine was calculated. Histology and other clinical data were collected from medical records. RESULTS The diagnostic performance of urinary CXCL9/cre in discriminating rejection from all other histological groups showed an ROC AUC value of 0.728 (95% CI 0.632-0.824, p<0.001), and a cut-off value 0.11 ng/mmol had the best sensitivity (76.9%) and specificity (73.1%). The ability of CXCL10/cre to discriminate transplant rejection from all other histological groups had ROC AUC value 0.73 (95% CI 0.63-0.84, P<0.001), the cut-off value 0.42 ng/mmol with best sensitivity (71.4%) and specificity (84.6%). CXCL9 and CXCL10 levels were also increased in patients with polyoma BK virus, recurrent AA amyloidosis, and thrombotic microangiopathy. Patients with higher CXCL9/cre (≥0.11 ng/mmol) and CXCL10/cre (≥0.42 ng/mmol) levels were at increased risk of transplant progression to ESRD (HR 3.25, 95% CI=1.27-8.36, P=0.01), irrespective of serum creatinine at the time of biopsy. CONCLUSIONS Urinary CXCL9/cre and CXCL10/cre were able to distinguished between patients with transplant rejection and those without rejection. High levels of urinary CXCL9/cre and CXCL10/cre were associated with worse allograft survival.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications., (© 2024. The Author(s).)

Objective: to review the literature regarding the relationship between pre- and post-transplant hypo-Albuminemia with various renal transplant-related infections., Materials and Methods: In a systematic review, we included the following keywords in the search: (Albumin*) AND (infection*) AND ("renal transplant" OR "renal transplantation" OR "renal transplants") OR ("kidney transplant" OR "kidney transplantation" OR "kidney transplants") OR "kidney grafting") with investigating databases including ProQuest, PubMed, Scopus, and Web of Science to May 2023. All adult patients who had renal transplantation were included. Albumin levels of infected (bacterial, fungal, or viral) patients and the type of infection should be reported in the included studies. The search strategy used in this review was reported by Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension (PRISMA-S). To conduct Meta-analyses, Stata version 17 was used. Also, DerSimonian-Laird random-effects models were used for this study. In our study, heterogeneity was quantified with I2 and τ2 statistics. Inconsistency across studies is quantified by I2 statistics, and the impact of heterogeneity on the meta-analysis is assessed by this quantification., Results: Overall, 18 studies were found to be reporting measures of association including risk ratio, odds ratio, and, hazard ratio. Among them, 10 and 8 studies reported bacterial and viral types of infection. The combined risk ratios were not statistically significant, in either type of infection. The mean (SD) of ages for bacterial and viral infections were found to be 45.3 (6.4) and 50.5 (7.6) years old, respectively., Conclusion: Hypoalbuminemia is not related to post-transplantation infections, and it seems that with adherence to proper pretransplant screening of recipients, vaccination, and post-transplant surveillance and prophylaxis, the impact of infections may be reduced.

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., (© 2024. The Author(s).)

Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and donor antigens and the attachment of the C1q complement fragment. This study aimed to determine the levels of circulating C1q immunocomplexes (CIC-C1q) and complement activation (CH50), in sensitized kidney transplant recipients (KTRs). In this cross-sectional study we used serum samples from KTRs with de novo or preformed DSAs ( n = 14), KTRs without DSAs ( n = 28), and 22 subjects with no history of chronic kidney disease (controls). C1q immunocomplexes and CH50 concentration in serum were measured with the enzyme immunoassay (EIA) kit MicroVue CIC-C1q (Quidel, Athens, OH, USA) and EIA kit MicroVue CH50 (Quidel, OH, USA), respectively. Higher concentrations of CIC-C1q was observed in KTRs with DSAs in comparison with controls and with KTRs with no DSAs (6.8 ± 2.7 and 4.8 ± 1.9 vs. 5.0 ± 1.2 μg Eq/mL, respectively, p < 0.01). We found no difference in CIC-C1q between KTRs with no DSAs and controls. CIC-C1q levels were positively correlated with DSA titer. CH50 levels were decreased in KTRs with DSAs in comparison with controls and KTRs with no DSAs (39 ± 15 vs. 68 ± 40 and 71 ± 34 U Eq/mL, respectively, p < 0.01). There was no difference in CH50 between DSA-negative KTRs and controls. Kidney transplant recipients with DSAs had increased serum levels of C1q immunocomplexes and increased classical pathway complement activation.

In the last few years, next-generation sequencing (NGS) has emerged as a technology for laboratory diagnosis of many culture-negative infections and slow-growing microorganisms. In this study, we describe the use of metagenomic NGS (mNGS) for rapid diagnosis of T. marneffei infection in a 37-year-old renal transplant recipient who presented with chronic pneumonia syndrome. Bronchoalveolar lavage for mNGS was positive for T. marneffei sequence reads. Prolonged incubation of the bronchoalveolar lavage revealed T. marneffei colonies after 6 days of incubation. Analysis of 23 cases of T. marneffei infections in renal transplant recipients from the literature revealed that the number of cases ranged from 1 to 4 cases per five years from 1990 to 2020; but increased rapidly to 9 cases from 2021 to 2023, with 7 of them diagnosed by NGS. Twenty of the 23 cases were from T. marneffei-endemic areas [southern part of mainland China (n = 9); Hong Kong (n = 4); northeastern India (n = 2); Indonesia (n = 1) and Taiwan (n = 4)]. For the 3 patients from non-T. marneffei-endemic areas [United Kingdom (n = 2) and Australia (n = 1)], they had travel histories to China and Vietnam respectively. The time taken for diagnosis by mNGS [median 1 (range 1 to 2) day] was significantly shorter than that for fungal culture [median 6 (range 3 to 15) days] (P = 0.002). mNGS is useful for picking up more cases of T. marneffei infections in renal transplant recipients as well as providing a rapid diagnosis. Talaromycosis is an emerging fungal infection in renal transplant recipients., (© 2024. The Author(s).)

Background: BK virus-associated nephropathy (BKVAN), caused by infection with or reactivation of BK virus, remains a challenge in kidney transplantation. Screening is recommended for all kidney transplant recipients. For those with clinically significant infection, reduction of immunosuppression is the cornerstone of management. There is no specific antiviral or immunomodulatory therapy sufficiently effective for routine use., Objectives: This review aimed to examine the benefits and harms of interventions for BK virus infection in kidney transplant recipients., Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 5 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov., Selection Criteria: All randomised controlled trials (RCTs) and cohort studies investigating any intervention for the treatment or prevention of BKVAN for kidney transplant recipients., Data Collection and Analysis: Two authors independently assessed the study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: Twelve RCTs (2669 randomised participants) were included. Six studies were undertaken in single centres, and six were multicentre studies; two of these were international studies. The ages of those participating ranged from 44 to 57 years. The length of follow-up ranged from three months to five years. All studies included people with a kidney transplant, and three studies included people with signs of BK viraemia. Studies were heterogeneous in terms of the type of interventions and outcomes assessed. The overall risk of bias was low or unclear. Intensive screening for the early detection of BK viraemia or BK viruria prevents graft loss (1 study, 908 participants: RR 0.00, 95% CI 0.00 to 0.05) and decreases the presence of decoy cells and viraemia at 12 months (1 study, 908 participants: RR 0.06, 95% CI 0.03 to 0.11) compared to routine care (high certainty evidence). No other outcomes were reported. Compared to placebo, fluoroquinolones may slightly reduce the risk of graft loss (3 studies, 393 participants: RR 0.37, CI 0.09 to 1.57; I 2 = 0%; low certainty evidence), probably makes little or no difference to donor-specific antibodies (DSA), may make little or no difference to BK viraemia and death, had uncertain effects on BKVAN and malignancy, but may increase the risk of tendonitis (2 studies, 193 participants: RR 5.66, CI 1.02 to 31.32; I 2 = 0%; low certainty evidence). Compared to tacrolimus (TAC), cyclosporin (CSA) probably makes little or no difference to graft loss and death, may make little or no difference to BKVAN and malignancy, but probably decreases BK viraemia (2 studies, 263 participants: RR 0.61, 95% CI 0.26 to 1.41; I 2 = 38%) and probably reduces the risk of new-onset diabetes after transplantation (1 study, 200 participants: RR 0.41, 95% CI 0.12 to 1.35) (both moderate certainty evidence). Compared to azathioprine, mycophenolate mofetil (MMF) probably makes little or no difference to graft loss and BK viraemia but probably reduces the risk of death (1 study, 133 participants: RR 0.43, 95% CI 0.16 to 1.16) and malignancy (1 study, 199 participants: RR 0.43, 95% CI 0.16 to 1.16) (both moderate certainty evidence). Compared to mycophenolate sodium (MPS), CSA has uncertain effects on graft loss and death, may make little or no difference to BK viraemia, but may reduce BKVAN (1 study, 224 participants: RR 0.06, 95% CI 0.00 to 1.20; low certainty evidence). Compared to immunosuppression dose reduction, MMF or TAC conversion to everolimus or sirolimus may make little or no difference to graft loss, BK viraemia or BKVAN (low certainty evidence). TAC conversion to sirolimus probably results in more people having a reduced BK viral load (< 600 copies/mL) than immunosuppression reduction (1 study, 30 participants: RR 1.31, 95% CI 0.90 to 1.89; moderate certainty evidence). Compared to MPS, everolimus had uncertain effects on graft loss and BK viraemia, may reduce BKVAN (1 study, 135 participants: 0.06, 95% CI 0.00 to 1.11) and may increase the risk of death (1 study, 135 participants: RR 3.71, 95% CI 0.20 to 67.35) (both low certainty evidence). Compared to CSA, everolimus may make little or no difference to BK viraemia, has uncertain effects on graft loss and BKVAN, but may increase the risk of death (1 study, 185 participants: RR 3.71, 95% CI 0.42 to 32.55; low certainty evidence). Compared to immunosuppression reduction, the leflunomide derivative FK778 may make little or no difference to graft loss, probably results in a greater reduction in plasma BK viral load (1 study, 44 participants: -0.60 copies/µL, 95% CI -1.22 to 0.02; moderate certainty evidence), but had uncertain effects on BKVAN and malignancy. Aggravated hypertension may be increased with KF778 (1 study, 46 participants: RR 8.23, 95% CI 0.50 to 135.40; low certainty evidence). There were no deaths in either group., Authors' Conclusions: Intense monitoring early after transplantation for BK viruria and BK viraemia is effective in improving BK virus infection outcomes as it helps with early detection of the infection and allows for a timely reduction in immunosuppression reduction. There is insufficient evidence to support any other intervention for BK virus infection in kidney transplant recipients., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mahler, Friedl, Nusshag, Speer, Benning, Göth, Schaier, Sommerer, Mieth, Mehrabi, Renders, Heemann, Krautter, Schwenger, Echterdiek, Zeier, Morath and Kälble.)

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., (© 2024. The Author(s).)

Competing Interests: Competing interests:: None declared.

Identification of early signatures of immune rejection represents a key challenge in the clinical management of kidney transplant. To address such an issue, we enrolled 53 kidney transplant recipients without signs of graft rejection, no infectious episodes and no change in the immunosuppressive regimen in the last 6 months. An extensive immune profile revealed increased activation of the T cells, a decreased amount and growth ability of the Treg and a higher level of the T R3-56 regulatory T cell subset, described by us as involved in the preferential control of cytotoxic T lymphocytes. In renal transplant recipients, the high level of the T R3-56 cells associates with a reduction in both the amount and the growth ability of the Treg. Moreover, when the transplanted subjects were categorised according to their stable or unstable disease status, as defined by changes in serum creatinine ≥0.2 mg/dL in two consecutive detections, a higher T R3-56 level and defective Treg growth ability were observed to characterise patients with unstable graft control. Further studies are required to substantiate the hypothesis that immune profiling, including T R3-56 evaluation, might represent a valuable diagnostic tool to identify patients at risk of developing significant anti-donor allo-immune responses.

Background: Intraoperative hypotension is associated with acute kidney injury after surgery. However, the definition (duration and magnitude) of hypotension during kidney transplantation (KT) surgery on early graft function remains unclear., Methods: We conducted a retrospective cohort study of KT recipients from December 1, 2009, to December 31, 2019. Exposure to intraoperative hypotension was characterized as the duration (minutes) of mean arterial pressure (MAP) <55, <65, <75, and <85 mmHg. Our co-primary outcomes were DGF-creatinine reduction ratio (DGF-CRR, <30% creatinine reduction, postoperative days 1 and 2), and DGF-dialysis (DGF-D, required dialysis within the week of KT for deceased donor recipients). Logistic regression models were fitted to assess this relationship between MAP and DGF., Results: We included 1602 KT (939 deceased donors, 663 living donors) and 23 were excluded. DGF-CRR occurred in 33% of patients. DGF-CRR was associated with MAP < 65 (>5 min: OR 1.77, 95% confidence interval [CI]: 1.39-2.30; 6-10 min: OR 1.67, 95% CI: 0.97-2.86; 11-20 min: OR 2.18, 95% CI: 1.31-3.63) in unadjusted and <55 mmHg (5 min: OR 1.85, 95% CI: 1.47-2.32; 5-10 min: OR 2.41, 95% CI: 1.65-3.53; 11-20 min: OR 2.36, 95% CI: 1.60, 3.48) in adjusted models. There was also a signal for increased risk of DGF-CRR at MAP < 75 (>5 min: OR 1.69, 95% CI: 1.02-2.80). DGF-D (incidence 35%) in deceased donor KT was not associated with hypotension., Conclusions: We found an association between intraoperative hypotension and DGF-CRR at a threshold MAP of 55 mmHg, with a consistent signal toward increased risk at both 65 and 75 mmHg, as indicated by unadjusted models., (© 2024 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)

Cytomegalovirus (CMV) infection is related to acute rejection and graft loss after kidney transplantation, though the underlying mechanism remains largely unknown. Some CMV strains produce a peptide that is identical to a peptide sequence found in the leader peptide of specific HLA-A and -C alleles. In this retrospective study of 351 kidney transplantations, we explored whether CMV-seropositive recipients without the VMAPRTLIL, VMAPRTLLL or VMAPRTLVL HLA class I leader peptide receiving a transplant from a donor with this peptide, faced an increased risk of T-cell-mediated rejection (TCMR) in the first 90 days after transplantation. An independent case-control cohort was used for validation (n = 122). The combination of recipient CMV seropositivity with the VMAPRTLIL peptide mismatch was associated with TCMR with a hazard ratio (HR) of 3.06 (p = 0.001) in a multivariable analysis. Similarly, the VMAPRTLLL peptide mismatch was associated with TCMR revealing a HR of 2.61 (p = 0.008). Transplantations featuring either a VMAPRTLIL or a VMAPRTLLL peptide mismatch had a significantly higher cumulative TCMR incidence (p < 0.0001), with the primary impact observed in the first 2 weeks post-transplantation. The findings could be validated in an independent cohort. Together, our data strongly suggest that CMV-positive recipients without an HLA peptide identical to a CMV peptide yet transplanted with a donor who does possess this peptide, have a significantly increased risk of early TCMR. Considering the prevention of such an leader peptide mismatch in these patients or adjusting immunosuppression protocols accordingly may hold promise in reducing the incidence of early TCMR., (© 2024 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

Introduction: Maribavir was recently approved by the FDA, expanding treatment options for post-solid-organ transplant refractory/resistant CMV. We sought to describe the post-marketing experience with maribavir at a large academic transplant center., Methods: This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia., Results: From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200 mg (SD-274 mg) in mycophenolate dosing with nonresponders having a mean increase of 167 mg (SD-764 mg)., Conclusions: Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/objectives: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status., Methods: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively ( p < 0.05)., Results: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI > 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88-8.52) for the MANO group and 74.59 (95% CI: 13.29-418.68) for the MAO group compared with the MHNO group., Conclusions: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.

Background: Recipient's VEGF-A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF-A gene polymorphism with rejection remained unelucidated till now., Methods: In this study, VEGF-A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n = 80) and without rejection (non-rejectors, n = 80). Blood VEGF-A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT-PCR, ELISA, and immunohistochemistry, respectively., Results: On comparing between the donor and rejectors, the polymorphic genotypes of VEGF -634 C>G [GG genotype, p < 0.0001; OR (95% CI) = 17.74 (5.16-60.96)]; VEGF -1154 G>A [AG genotype, p < 0.0001, OR (95% CI) = 16.07 (3.68-70.15)]; VEGF +936 C>T [CT genotype, p < 0.0001, OR (95% CI) = 178.64 (23.28-1370.9), and TT genotype, p < 0.0001; OR (95% CI) = 3149 (278.91-35 553)]; VEGF -1455 T>C [CC genotype, p value = 0.0464, OR (95% CI) = 3.13 (1.07-9.10)]; VEGF -2578 C>A [CA genotype, p = 0.0426, OR (95% CI) = 4.62 (1.03-20.59), and AA genotype, p value < 0.0001, OR (95% CI) = 21.89 (4.94-97.04)]; VEGF -2549 18 bp Insertion/Deletion [ID genotype, p value < 0.0001, OR (95% CI) = 27.27 (3.61-205.73) and DD genotype, p value < 0.0001, OR (95% CI) = 25.18 (3.30-191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non-rejectors, GA genotype of VEGF -1190 G>A and TC genotype of VEGF -1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non-rejectors, CG genotype of VEGF -634 C>G, AG of VEGF -1154 G>A; GA of VEGF -1190 G>A were associated with rejection. The blood VEGF-A mRNA and plasma VEGF levels were higher in the rejectors group compared to non-rejectors., Conclusions: Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Glomerulonephritis (GN) is one of the main causes of end-stage renal disease worldwide and therefore a frequent cause of kidney transplantation, with the possibility of recurrence of GN (Recurrent Glomerulonephritis [GNR]) in the transplanted kidney. The purpose of this study was to identify the clinic and pathological characteristics of GNR in a population of transplant patients., Materials and Methods: A descriptive, retrospective study was carried out in 109 patients in whom GNR was documented in the transplanted kidney demonstrated by biopsy during the period between 1998-2021., Results: Of 109 patients, the most frequent GNR was GNIgA, in 38.5% (42), followed by FSGS with 31.2% (34); These same entities were the ones that presented the greatest graft dysfunction, with 50% (21) and 26.2% (11) respectively. The ranges of proteinuria indicated by the biopsy were 31.2% (34) with a range of 500 to 3500mg/24h and 34.9% (38) with proteinuria >3500mg/24h. In relation to the time elapsed between the transplant and the diagnosis of GNR, 33% (36) of the cases were >5 years, followed by 1 to 5 years in 26.6% (29). Recurrence in patients with GNIgA occurred mostly after 5 years post-transplant with 45.2% (19) and for FSGS it was between 1 and 6 months., Conclusion: We found a general frequency of GNR presentation similar to those reported by other centers where biopsies are performed for clinical indication, finding that the GN that recurred most frequently are GNIgA and FSGS., (Copyright © 2024 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Most of the world's adult population is latently infected by the BK polyomavirus. It causes asymptomatic infection in healthy individuals but emerged as a threat to kidney transplant recipients because of virus-associated nephropathy caused by immunosuppressive therapy. In these conditions, when a functional cellular response is impaired by immunosuppression, neutralizing antibodies may play a major role because they can directly prevent infection of target cells, independently of cell-mediated immunity, by binding to the viral particles. Studying the contribution of anti-BK virus neutralizing antibodies in viral control has long been hampered by the lack of convenient in vitro models, but major progress has been made in the past decade. The four BK virus genotypes have been demonstrated to behave as distinct serotypes. A low recipient neutralizing antibody titer against the donor's serotype before kidney transplant has been significantly associated with BK virus replication after transplant. Different mechanisms exploited by the BK virus to evade neutralizing antibodies have been described. Recent studies also support the potential benefit of administering intravenous Igs or monoclonal neutralizing antibodies as a therapeutic strategy, and more interestingly, this could also be used as preventive or preemptive therapy before advanced kidney damage has occurred. Besides, neutralizing antibodies could be induced by vaccination. In this review, we summarize accumulated knowledge on anti-BK virus neutralizing antibodies as well as their clinical importance and therapeutic potential for kidney transplant recipients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Competing Interests: The authors declare no funding or conflicts of interest.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Urinary tract infections (UTIs) are the second most common cause of graft dysfunction, accounting for significant morbidity, and are associated with poor graft and patient survival. This study aimed to assess the association between post-renal transplant UTI and graft outcomes., Methods: We examined the effect of UTIs on graft outcomes in patients who underwent renal transplantation surgery between January 2010 and December 2022. The study population included 349 renal transplantations, of which 74 experienced 140 UTI events. Based on the number of UTI episodes, patients were categorized into three groups., Results: Of the 349 recipients, 275 (74.4%) had no UTI, 47 (18.8%) had non-recurrent UTIs (NR-UTIs), and 27 (6.8%) had recurrent UTIs (R-UTIs). Kaplan-Meier survival analysis showed that post-KT UTI status was a significant factor in graft survival, death-censored graft survival, and patient survival after a follow up of 5 years (log rank, P < 0.001). R-UTIs were associated with very poor graft survival and patient survival when compared with no UTI after a follow up of 5 years (hazard ratio [HR], 1.506; 95% confidence interval [CI], 1.233-1.840; P < 0.001 & HR, 1.529; 95% CI, 1.227-1.905; P = 0.001). R-UTIs were more likely to be associated with multi-drug resistant Gram-negative organisms (Klebsiella pneumonia or Escherichia coli) with resistance to nitrofurantoin (RR, 2.753; 95% CI, 1.257-6.032; P = 0.01) and carbapenem (RR, 2.064; 95% CI, 0.988-4.314; P = 0.05)., Conclusion: Compared to no UTI, R-UTIs were associated to worse graft and patient outcomes after a follow-up of 5 years, whereas NR-UTIs were associated with poor graft and patient outcomes in the long term.

Post-transplant recurrence of focal segmental glomerular sclerosis (FSGS) is a major challenge in the field of kidney transplantation. Currently, the most reliable predictor of FSGS recurrence is disease recurrence in a previous allograft. Recent studies suggest a possible causal role of anti-nephrin autoantibodies in the primary disease (primary FSGS and minimal change disease), as well as post-transplant recurrence of FSGS. In this issue of Kidney International, Batal et al. evaluate pretransplant anti-nephrin autoantibodies as a specific predictor of FSGS recurrence and demonstrate colocalization of nephrin and punctate IgG in anti-nephrin-positive patients with disease recurrence., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia., Methods: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis., Results: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death., Conclusion: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.

Objectives: Ferroptosis plays a pivotal role in the pathogenesis of renal ischemia-reperfusion injury, where the processes are mediated by free ferrous ions and mitochondrial-released reactive oxygen species. However, the administration of high doses of cyclosporine A (CsA) or deferoxamine (DFO) poses a significant risk of renotoxicity. In contrast, low doses of DFO act as a ferrous iron chelator, and CsA functions as a mitochondrial reactive oxygen species blocker. This study aims to explore the potential protective effects of donor treatment with low-dose CsA, DFO, or their combination against ischemia-reperfusion injury during renal transplantation in a rat model., Materials and Methods: In an ex vivo cold storage (CS) model utilizing renal slices, the impact of incorporating DFO, CsA, and a combination of both into the University of Wisconsin solution was assessed through the measurement of lactate dehydrogenase leakage. Additionally, their potential benefits were investigated in a rat donation after circulatory death (DCD) kidney transplant model, where the extent of damage was evaluated based on graft function, tubular necrosis, and inflammation., Results: The co-administration of DFO and CsA effectively decreased the release of lactate dehydrogenase induced by CS ( P ≥ .05). In the in vivo model, this combined supplementation demonstrated a mitigating effect on reperfusion injury, evidenced by lower blood urea nitrogen levels and acute tubular necrosis scores compared to the control group (allP ≤ .05). Furthermore, the combined treatment significantly reduced apoptotic levels compared to the control group (P ≥ .05)., Conclusions: The combined treatment with DFO and CsA mitigated the cold ischemia-reperfusion injury in the DCD kidney. Hence, this presents a new strategy for the CS of DCD kidney in clinical transplants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories., Methods: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group., Results: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036)., Conclusions: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The effect of belatacept on BK polyomavirus (BKPyV) control remains largely unknown., Methods: This is a propensity matched retrospective cohort study in adult kidney transplant recipients (KTR) transplanted between 2016-2020 who received a belatacept- versus tacrolimus-based immunosuppression regimen. A continuous time multi-state Markov model was used to evaluate BKPyV replication dynamics (BKPyV-dyn). Three BKPyV-dyn states were defined: BKPyV-dyn1 (viral load <3 log 10 ), BKPyV-dyn2 (viral load ≥ 3 log 10 and ≤4 log 10 ), and BKPyV-dyn3 (viral load >4 log 10 )., Results: Two hundred eighty KTR on belatacept- and 280 KTR on tacrolimus-based regimens were compared. The probability of transitioning between BKPyV-dyn states and time spent in each state in both groups was comparable. Total duration in BKPyV-dyn-1 was 632.1 days (95% CI 612.1, 648.5) for belatacept versus 615.2 days (95% CI 592.5, 635.8) for tacrolimus, BKPyV-dyn-2 was 49.2 days (95% CI 41.3, 58.4) for belatacept versus 55.6 days (95% CI 46.5, 66.8) for tacrolimus, and BKPyV-dyn-3 was 48.7 days (95% CI 37.1, 363.1) for belatacept versus 59.2 days (95% CI 45.8, 73.5) for tacrolimus. BKPyV associated nephropathy (PyVAN) occurred in 3.9% in belatacept- and 3.9% tacrolimus-treated KRT (P > .9)., Conclusions: Compared with tacrolimus-based immunosuppression, belatacept based immunosuppression was not associated with increased risk of BKPyV-DNAemia or nephropathy., (© 2024 Wiley Periodicals LLC.)

Purpose of Review: The number of cases of visceral leishmaniasis associated with transplant-associated immunosuppression has increased in recent years. Reviewing and updating the latest developments in its diagnostic management, treatment, and follow-up is necessary and relevant., Recent Findings: Visceral leishmaniasis cases associated with non-HIV immunosuppression are a growing cause of the parasitic infections, and the transplant patients are included in this context. These have been described especially in kidney transplantation. Liposomal amphotericin B is the first-line treatment. Due to immunosuppression, these patients often suffer from recurrent infections. The use of markers that indicate whether the patient has developed an adequate cellular response against Leishmania after treatment seems to be good biomarkers of cure and useful for monitoring and guiding secondary prophylaxis., Summary: There is a lack of consensus regarding the need for leishmaniasis screening in donors and recipients and the indications for secondary prophylaxis. The study of new biomarkers of cure may be useful in all three contexts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)-negative (-) recipients who received HCV NAT-positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT- recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution., Methods: This was an Institutional Review Board-approved, single-center, retrospective case-control study of HCV NAT- kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation., Results: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT-) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95-1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient-, D+/R-)., Conclusion: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV., (© 2024 Wiley Periodicals LLC.)

Background: Although it is acknowledged that ischemia-reperfusion injury is the primary pathology of cold storage-associated kidney transplantation, its underlying mechanism is not well elucidated., Methods: To extend the understanding of molecular events and mine hub genes posttransplantation, we performed bulk RNA sequencing at different time points (24 h, day 7, and day 14) on a murine kidney transplantation model with prolonged cold storage (10 h)., Results: In the present study, we showed that genes related to the regulation of apoptotic process, DNA damage response, cell cycle/proliferation, and inflammatory response were steadily elevated at 24 h and day 7. The upregulated gene profiling delicately transformed to extracellular matrix organization and fibrosis at day 14. It is prominent that metabolism-associated genes persistently took the first place among downregulated genes. The gene ontology terms of particular note to enrich are fatty acid oxidation and mitochondria energy metabolism. Correspondingly, the key enzymes of the above processes were the products of hub genes as recognized. Moreover, we highlighted the proximal tubular cell-specific increased genes at 24 h by combining the data with public RNA-Seq performed on proximal tubules. We also focused on ferroptosis-related genes and fatty acid oxidation genes to show profound gene dysregulation in kidney transplantation., Conclusions: The comprehensive characterization of transcriptomic analysis may help provide diagnostic biomarkers and therapeutic targets in kidney transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico., Methods: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS., Results: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-β-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis., Conclusion: Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis., (© 2024 Wiley Periodicals LLC.)

Purpose: Persistent hyperparathyroidism (PTHPT) in kidney transplant recipients is associated with bone loss, graft dysfunction and cardiovascular mortality. There is no clear consensus on the management of PTHPT. Accurate risk prediction of the disease is needed to support individualized treatment decisions. We aim to develop a useful predictive model to provide early intervention for hyperparathyroidism in these patients., Methods: We retrospectively analyzed 263 kidney transplantations in the urology department of China-Japan Friendship Hospital from January 2018 to December 2022. The overall cohort was randomly assigned 70% of the patients to the training cohort and 30% to the validation cohort. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for PTHPT and to construct the predictive model. This model was assessed regarding discrimination, consistency, and clinical benefit., Results: The occurrence of PTHPT was 25.9% (68 out of 263 patients) in this study. Dialysis duration, postoperative 3-month intact parathyroid hormone (iPTH), 3-month corrected calcium (cCa), and 3-month phosphorus (P) are independent risk factors for the development of PTHPT. The nomogram showed good discrimination with the area under the curve (AUC) value of 0.926 in the training cohort and 0.903 in the validation cohort. The calibration curve and decision curve also showed that the model was well-evaluated., Conclusion: We developed a validated nomogram model to predict PTHPT after kidney transplantation. This can help the clinic prevent and control PTHPT early and improve patients' prognosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status., Methods: We assessed the bias and P 30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement., Results: In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m 2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m 2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m 2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m 2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m 2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m 2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m 2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations., Conclusion: In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Delayed graft function (DGF) is a common condition that necessitates dialysis during the first week after transplantation. Although DGF rarely occurs following living-donor kidney transplantation (LDKT), it may eventually lead to acute or chronic graft rejection. This study aimed to assess the risk factors for DGF in patients who underwent LDKT., Methods: A systematic review and meta-analysis of studies published before August 2022 was conducted using the PubMed, Science Direct, Cochrane, and Directory of Open Access Journal (DOAJ) databases. The review included studies that assessed the incidence of DGF following LDKT, and examined its risk factors, while excluding studies involving deceased donors. Potential risk factors were analyzed using pooled mean differences or odds ratios with 95% confidence intervals (CIs). Review Manager 5.3 was used for the meta-analysis., Results: Among the 13 included studies, 3685 cases of DGF were identified in a total of 113,261 patients (3.25%). Potential risk factors for DGF following LDKT were examined across several aspects, including donor, recipient, donor/recipient relationship, and immunological and intraoperative factors. The identified risk factors included older donors (P = 0.07), male recipients (P < 0.0001), higher recipient body mass index (BMI) (P < 0.0001), non-white recipients (P < 0.0001), pre-existing diabetes (P < 0.0001), pre-existing hypertension (P = 0.01), history of dialysis (P < 0.0001), re-transplantation (P = 0.004), unrelated donor/recipient (P = 0.02), ABO incompatibility (P < 0.0001), higher panel reactive antibody (PRA) levels (P < 0.0001), utilization of right kidney (P < 0.0001), and longer cold ischemia time (CIT) (P = 0.004)., Conclusion: Several factors related to the donor, recipient, donor/recipient relationship, and immunological and intraoperative aspects were identified as potential risk factors for the development of DGF following LDKT. Addressing and optimizing these factors may improve the long-term outcomes of LDKT., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF)., Methods: Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF., Results: A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF., Conclusions: This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest., Competing Interests: G.W. is supported by an NHMRC Career Development Fellowship. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Patients with lower urinary tract malformations (LUTM) were suspended from kidney transplantation (KT) programs in the past due to various concerns. Consequently, only a limited number of studies have explored this topic at hand. In this study, our objective was to perform a systematic review (SR) to evaluate the current evidence regarding KT outcomes as well as patient survival (PS), postoperative complications and urinary tract infections (UTI) in individuals with childhood LUTM., Methods: The search encompassed databases of Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify all studies reporting outcomes on KT for patients with LUTM. The research included articles published in English from January 1995 till September 2023., Results: Of the 2634 yielded articles, 15 met the inclusion criteria, enrolling a total of 284,866 KT patients. There was significantly better 5-year graft survival (GS) in recipients with LUTM compared to the control group (RR, 1.04; 95% CI 1.02-1.06); while GS at 1-year and 10-year, and PS at 1-year, 5-year and 10-year were similar between groups. On the other hand, the postoperative UTI rate was significantly higher in the LUTM group (RR: 4.46; 95% CI 1.89-10.51). However, data on serum creatinine and estimated glomerular filtration rate on follow-up were insufficient., Conclusion: GS and PS rates appear to be similar in patients with childhood LUTM and those with normal lower urinary tract functions. Despite a higher postoperative UTI rate within this patient group, it appears that this has no effect on GS rates., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.

Objectives: We aimed to evaluate the changes in renal cortical microperfusion and quantitative contrast-enhanced ultrasonography (CEUS) parameters after kidney transplantation, and to determine the evidence-based value of CEUS in predicting renal dysfunction., Methods: The Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched for relevant studies published from 2000 to 2023 on the use of CEUS to assess the renal cortical microcirculation after kidney transplantation. Subject terms and related keywords were combined, and a meta-analysis and systematic review were performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines., Results: The search yielded six studies involving 451 patients with moderate to high overall quality. The peak intensity (standardized mean difference [SMD]: -0.64, 95% confidence interval [CI] -1.13 to -0.15, p = 0.01) of CEUS was significantly lower in patients with renal dysfunction than in those with stable renal function. However, the time to peak (SMD: 0.28, 95% CI 0.04 to 0.52, p = 0.02) was significantly shorter in patients with renal dysfunction than in those with stable renal function. The total renal cortical microperfusion and renal cortical perfusion intensity were decreased, and the perfusion time was prolonged, in patients with renal dysfunction after kidney transplantation., Conclusion: CEUS parameters can reflect real-time changes in renal cortical microperfusion, thus providing a basis for the early diagnosis of renal dysfunction after kidney transplantation., (© 2024 Wiley Periodicals LLC.)

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years., Methods: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses., Results: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection., Conclusion: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration., (© 2024 Wiley Periodicals LLC.)

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m 2 , 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d. Proteinuria increased with circulating CD38 + plasma cells and responded to an additional daratumumab dose. Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy. Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access. After treatment with obinutuzumab and daratumumab (1 dose each), she achieved stable complete remission (0.3 g/d proteinuria) with persistent plasmapheresis discontinuation. These cases suggest the potential of combining obinutuzumab with daratumumab for the treatment of recurrent FSGS., Competing Interests: Declaration of competing interests The authors of this manuscript have no conflicts of interest to disclose as described in the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients., Materials and Methods: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study., Results: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m 2 . In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy., Conclusion: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Purpose: Diarrhea is an important cause of morbidity and mortality in immunocompromised patients. After including sapovirus to the viral gastroenteritis screening of our institution's laboratory, we noticed an increase in sapovirus infections among kidney transplant recipients. Therefore, we assumed former gastrointestinal tract infections with unidentified pathogens could have been caused by sapovirus. To better understand the characteristics of a sapovirus infection in a high-risk group we initiated this study., Methods: Over a period of 6 months, all transplant recipients with diarrhea and later identified viral/unknown pathogens were included. Kidney function, levels of immunosuppressants and  c-reactive protein, acid-base balance, onset of symptoms and time of hospitalization were analyzed., Results: Among 13 hospitalized kidney transplant recipients sapovirus was detected in four patients, while in the remaining nine, three were diagnosed with norovirus, one with cytomegalovirus, one with inflammatory bowel disease and in four patients no pathogen was identified. Even though statistically not significant, creatinine levels at admission tended to be higher in sapovirus patients (median: sapovirus: 3.3 mg/dl (1.3; 5.0), non-sapovirus: 2.5 mg/dl (1.1; 4.9), p = 0.710). Also, Tacrolimus levels showed the same trend (sapovirus: 13.6 ng/ml (12.9; 13.6), non-sapovirus: 7.1 ng/ml (2.6; 22.6), p = 0.279). On discharge creatinine levels improved equally in both groups (sapovirus: 1.7 mg/dl (1.4; 3.2), non-sapovirus: 2 mg/dl (1.0; 3.6), p = 0.825)., Conclusion: In high-risk patients, early symptomatic treatment remains crucial to protect the transplant`s function. In our cohort all patients recovered well. Larger cohorts and longer follow-up times are needed to detect the long-term consequences and a potential need for further research regarding specific treatment., Trial Registration: The study has been registered on DRKS (trialsearch.who.int), Reg. Nr. DRKS00033311 (December 28th 2023)., (© 2024. The Author(s).)