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The article presents a retrospective study which examines the effect of concentration-controlled treatment on mycophenolic acid (MPA) exposure and renal outcome in patients with lupus nephritis. It mentions the administration of intravenous cyclophosphamide to 16 systemic lupus erythematosus (SLE) patients with lupus nephritis, followed by mycophenolate mofetil. It notes that concentration-controlled dose adjustments has contributed to the optimized MPA exposure and improved renal outcome.

Behavioral sensitization, the progressive and enduring enhancement of certain stimulant-induced behaviors following repetitive drug use, is mediated in part by dopaminergic pathways known to play a role in drug dependence. It has been theorized that sensitization underlies the development of drug craving and initiates addictive behaviors of drug dependence. We propose that down-regulation of D3 dopamine receptor function contributes to sensitization. Rodent locomotion is regulated by the opposing influence of dopamine receptor subtypes, with D3 stimulation inhibiting and concurrent D1/D2 receptor activation stimulating locomotion. The D3 receptor has greater occupancy than D1 or D2 receptors following stimulant drug administration. Sensitization may therefore result in part from greater accommodation of the inhibitory D3 receptor 'brake' on locomotion, leading to progressive locomotion increase following repeated stimulant exposure. Further study is needed to test this proposed model, and to clarify the role of individual dopamine receptor subtypes in sensitization and drug dependence. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is associated with adverse outcomes in kidney transplant recipients (KTR), including graft failure, morbidity, and mortality. Since both exercise training and dietary modifications have the potential to improve redox status, we aimed to investigate the potential mitigating effects of exercise or exercise plus diet intervention on circulating levels of free thiols (R-SH) as marker of systemic redox status in KTR., Methods: We conducted a post-hoc analysis of the Active Care after Transplantation (ACT) study, a randomized controlled lifestyle intervention trial which proved to enhance physical functioning of KTR. Systemic R-SH levels were quantified at baseline, 3-months, and 15-months (end of study) using a colorimetric detection method. Estimated marginal means (EMM) were reported using general linear mixed models., Results: KTR were randomized to usual care (n=40), exercise intervention (n=54), or exercise plus diet intervention (n=55). At 3 months post-baseline, systemic R-SH concentrations decreased significantly in the control group, while the intervention groups showed a less pronounced decrease, although the difference compared to control nearly reached statistical significance in either the exercise intervention group (EMM +20.2 μM (95%CI -1.4, +41.9), P=0.067) or the exercise plus diet intervention group (EMM +18.9 μM (95%CI -2.7, +40.4), P=0.086). At 15 months post-baseline, R-SH concentrations further decreased in the exercise intervention group, resulting in a difference compared to control of +9.0 μM (95%CI -14.4, +32.3; P=0.45), whereas R-SH concentrations increased to above baseline in the exercise plus diet intervention group, with a statistically significant difference compared to control of +32.8 μM (95%CI +9.4, +56.2; P=0.006)., Conclusions: Lifestyle changes involving exercise and diet positively impacted systemic R-SH, suggesting that reducing oxidative stress through lifestyle interventions could potentially contribute to clinical benefits in KTR., (Copyright © 2025. Published by Elsevier Inc.)

Background and Hypothesis: A more pronounced short-term increase in single-kidney GFR (ΔskGFR) has been associated with better long-term kidney function in living kidney donors. Whether this also applies to non-donors is unknown. We evaluated if ΔskGFR is associated with long-term risk of eGFR decline in individuals undergoing unilateral nephrectomy., Methods: This study included 1777 participants from the SCREAM cohort who underwent radical unilateral nephrectomy in Stockholm between 2006-2021. The ΔskGFR was calculated as the early (1-6 months) post-nephrectomy eGFR minus 50% of the pre-nephrectomy eGFR. Multivariable Cox regression was used to study the association between Δsk-GFR and the subsequent risk of progressive eGFR decline, defined as composite of an eGFR decline > 30% compared to the early (6 months) post-nephrectomy eGFR or kidney failure., Results: Mean age at nephrectomy was 68 ± 11 years, 40% were female, 92% had kidney cancer, and median (IQR) pre-nephrectomy eGFR was 76 (61-89) mL/min/1.73m2. Median Δsk-GFR was 11 (7-20) mL/min/1.73m2. Pre-nephrectomy determinants of Δsk-GFR were age (inverse association) and pre-nephrectomy eGFR (positive association). During a median follow-up of 5 years (range 0.6-15 years), 178 participants developed progressive eGFR decline. Individuals with a Δsk-GFR above the median had a lower rate of progressive eGFR decline (adjusted HR: 0.58, 95% CI: 0.42-0.80), compared to those with a Δsk-GFR below the median, independent of baseline eGFR and age., Conclusions: A stronger increase in single-kidney eGFR early after unilateral nephrectomy was associated with a lower long-term risk of progressive eGFR decline. Evaluation of Δsk-GFR could help identify patients at higher risk of progressive kidney function decline following unilateral nephrectomy., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Background: KEPs (kidney exchange programs) facilitate living donor kidney transplantations (LDKT) for patients with incompatible donors, who are typically higher risk than non-KEP patients because of higher sensitization and longer dialysis vintage. We conducted a comparative analysis of graft outcomes and risk factors for both KEP and non-KEP living donor kidney transplants., Methods: All LDKTs performed in the Netherlands between 2004-2021 were included. The primary outcome measures were one-, five- and 10-year death censored graft survival (DCGS). The secondary outcome measures were delayed graft function (DGF), graft function, rejection rates and patient survival. We used a propensity score matching model to account for differences at baseline., Results: Out of 7536 LDKTs, 694 (9%) were transplanted via the KEP. Ten-year graft survival was similar for KEP 0.916 (95% CI: 0.894 - 0.939) and non-KEP 0.919 (0.912 - 0.926, p = 0.82). We observed significant differences in five-year rejection (12% vs 7%), and five-year patient survival (KEP: 84%, non-KEP: 90%), which was non-significant after propensity score matching. Significant risk factors for lower graft survival included high donor age, re-transplantations, extended dialysis vintage, higher panel reactive antibodies, and nephrotic syndrome as the cause of end-stage kidney disease ., Conclusions: Transplantation via KEP offers a viable alternative for patients lacking compatible donors, avoiding specific and invasive pre- and post-transplant treatments. KEP's similar survival rate to non-KEP suggests prioritizing KEP LDKT over deceased donor kidney transplantation, desensitization, and dialysis. However, clinicians should consider the identified risk factors when planning and managing pre- and post-transplant care to enhance patient outcomes. Thus, we advocate for the broad adoption of KEP and establishment in regions lacking such programs, alongside initiation and expansion of international collaborations., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background: Alemtuzumab can be an alternative to rabbit anti-thymocyte globulin (rATG) to treat severe or glucocorticoid-resistant acute T cell-mediated kidney transplant rejection (TCMR). Yet, there are few reports in which these two treatments are evaluated let alone, compared. This study describes the real-world clinical experience of both therapies and compares their efficacy and toxicity., Methods: Kidney transplant recipients of two Dutch transplant centers who received lymphocyte-depleting antibody therapy for severe or glucocorticoid-resistant TCMR were retrospectively evaluated. In the first, alemtuzumab was the standard treatment for this indication, in the second, it was rATG. Patient survival, graft survival and function, and the occurrence of infections and malignancies were reported and compared., Results: One hundred and forty-three patients treated with alemtuzumab and 57 patients with rATG were evaluated. Patient survival was not significantly different during follow-up (p = 0.55), and 5-year survival rates were 71.0% (95% confidence interval [CI]: 63.0-79.9) after alemtuzumab and 70.7% (95% CI: 58.3-85.7) after rATG. Graft survival was not significantly different during follow-up either (p = 0.24), and 5-year graft loss rates were 32.3% (95% CI: 24.2-40.5) after alemtuzumab and 29.2% (95% CI: 16.0-42.4) after rATG. The occurrence of infections and malignancies did not differ between groups., Conclusion: Mostly, severe TCMRs have good long-term graft survival and function after either alemtuzumab or rATG therapy. No significant differences between the two therapies were found in this real-world clinical experience. Alemtuzumab is an effective alternative to rATG for the treatment of severe TCMR., (© 2024 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)

Background: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR., Methods: We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed)., Results: Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine., Conclusions: Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Muscles are crucial for daily activities, and kidney transplant recipients (KTRs) often have reduced muscle mass and strength. We aimed to investigate the potential relationship of muscle mass and strength with physical health-related quality of life (HRQoL) in KTRs., Methods: Data from the TransplantLines Biobank and Cohort Studies were used. Muscle mass was assessed using appendicular skeletal muscle mass index (ASMI) and 24-hour urinary creatinine excretion rate index (CERI). Muscle strength was assessed by handgrip strength index (HGSI). HRQoL was measured using Short Form 36 physical component score (PCS)., Results: We included 751 KTRs (61% male; mean age, 56 ± 13 years, median of 3 years post-transplant). Ordinary least squares regression analyses demonstrated that lower ASMI, CERI, and HGSI were all nonlinearly associated with lower PCS, independent of potential confounders and each other. Below median values, ASMI, CERI, and HGSI were each associated with PCS; whereas above median values, associations were less pronounced. Compared to the 50th percentile, a decrease to the 10th percentile was associated with a change in PCS of -4.8% for ASMI ( P  = 0.011), of -5.1% for CERI ( P  = 0.008), and -13.2% for HGSI ( P  < 0.001), whereas an increase to the 90th percentile was associated with a change in PCS of only +0.7% for ASMI ( P  = 0.54), of +3.6% for CERI ( P  = 0.05), and -0.4% for HGSI ( P  = 0.73)., Conclusion: Low muscle mass and strength are potentially modifiable risk factors for impaired physical HRQoL in KTRs. The nonlinear associations suggest that KTRs with low muscle mass or strength may particularly benefit from (p)rehabilitation interventions to improve HRQoL., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Pregnancy after orthotopic liver transplantation (OLT) puts the mother, child, and transplanted organ at risk. Little is known about long-term outcomes. We performed a nationwide retrospective cohort study to evaluate short-term and long-term outcomes of post-OLT pregnancies. The secondary aim was to assess predictors for adverse pregnancy outcomes. A composite outcome of preeclampsia, preterm birth, low birth weight, and neonatal intensive care unit admission was made. Survival of women who received a transplant at <50 years of age with and without pregnancy after OLT were compared (Dutch Organ Transplantation Registry data). Descriptive statistics, regression analysis, Kaplan-Meier and log-rank analysis, and generalized estimating equation analysis were used. Among the included 70 women with 113 pregnancies >20 weeks of gestation, hypertension occurred in 20% and preeclampsia in 12%. The live birth rate was 87%; 33% were preterm, and 23% had low birth weight. Long-term follow-up (median 10 y [IQR: = 4-14]) showed small changes in serum creatinine and bilirubin ( p < 0.001). Sixteen mothers (23%) died during follow-up (median 8 y [IQR: = 4-12]), with all their children aged <18 years. No difference in survival was found when comparing women with and without pregnancy after OLT. The composite outcome occurred in 43/98 of pregnancies. Higher body mass index (BMI) and maternal age at conception increased the composite outcome risk (OR: 1.24, p < 0.01, and OR: 1.25, p = 0.01, respectively). To conclude, pregnancy after OLT does not seem to influence long-term outcomes of graft, kidney function, or patient survival in most cases. However, although pregnancy does not seem to impact survival after OLT, we do show that a substantial number of children will lose their mothers early in life. We believe this is important for pregnancy couseling of patients with an OLT and their partners., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Robust evidence for interventions to improve health-related quality of life (HRQoL) in people who receive a kidney transplant is scarce. We aimed to assess the effects of a lifestyle intervention in this context., Methods: We conducted a multicentre, open-label, parallel-group, randomised controlled trial among people who have received a kidney transplant. Participants from six hospitals across the Netherlands were randomly assigned 1:1:1 by an independent company into: usual care, exercise, and exercise plus diet. The exercise intervention encompassed two phases, a 3-month supervised exercise programme (twice weekly) followed by 12 months of lifestyle coaching, with 15 months of additional dietary counselling (12 sessions) for the exercise plus diet group. The primary outcome was HRQoL-domain physical functioning, assessed using the 36-item Short Form Survey at 15 months., Findings: From Oct 12, 2010 to Nov 18, 2016, 221 participants who had received a kidney transplant (138 [62%] male and 83 [38%] female, with a mean age of 52·5 [SD 13·5] years, who were a median of 5·5 [IQR 3·6-8·4] months post-transplant) were included and randomly assigned to usual care (n=74), exercise intervention (n=77), and exercise plus diet intervention (n=70). In the intention-to-treat analyses, at 15 months post-baseline, no significant differences in HRQoL-domain physical functioning were found for the exercise group (5·3 arbitrary units, 95% CI -4·2 to 14·9; p=0·27), and the exercise plus diet group (5·9 arbitrary units, -4·1 to 16·0; p=0·25) compared with control. Safety outcomes showed no safety concerns. After 3 months of supervised exercise intervention, HRQoL-domain physical functioning improved in the exercise group (7·3 arbitrary units, 95% CI 1·2 to 13·3; p=0·018) but not in the exercise plus diet group (5·8 arbitrary units, -0·5 to 12·1; p=0·072)., Interpretation: A lifestyle intervention is safe and feasible in people who have received kidney transplants, paving the way for lifestyle intervention studies in other multimorbid populations with polypharmacy. However, improving HRQoL for people who have received a kidney transplant is challenging. The lifestyle interventions in the current study did not show significant improvements in HRQoL at the end of the study at the total group level., Funding: Dutch Kidney Foundation, Innovation Fund of the Dutch Medical Insurance Companies, and University Medical Center Groningen., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Ex vivo normothermic machine perfusion (NMP) is a promising tool for assessing an isolated kidney prior to transplantation. However, there is no consensus on the perfusate's optimal oxygen-carrying capacity to support renal function. To investigate the association of hemoglobin levels with renal function parameters, a retrospective analysis of isolated, normothermically, perfused porcine kidneys was performed., Methods: Between 2015 and 2021, a total of 228 kidneys underwent 4 h of NMP with perfusates that varied in hemoglobin levels. A generalized linear model was used to determine the association of hemoglobin levels with time-weighted means of renal function markers, such as fractional sodium excretion (FENa) and creatinine clearance (CrCl). Stratified by baseline hemoglobin level (<4.5, 4.5-6, or >6 mmol/L), these markers were modeled over time using a generalized linear mixed-effects model. All models were adjusted for potential confounders., Results: Until a hemoglobin level of around 5 mmol/L was reached, increasing hemoglobin levels were associated with superior FENa and CrCl. Thereafter, this association plateaued. When hemoglobin levels were categorized, hemoglobin <4.5 mmol/L was associated with worse renal function. Hemoglobin levels were neither significantly associated with proteinuria during NMP nor with ATP levels at the end of NMP. Hemoglobin levels >6 mmol/L showed no additional benefits in renal function., Conclusion: In conclusion, we found an association between baseline hemoglobin levels and superior renal function parameters, but not injury, during NMP of porcine kidneys. Furthermore, we show that performing a retrospective cohort study of preclinical data is feasible and able to answer additional questions, reducing the potential use of laboratory animals., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Kidney transplant recipients (KTRs) experience more fatigue, anxiety, and depressive symptoms and lower concentration and health-related quality of life (HRQoL) compared with the general population. Anemia is a potential cause that is well-recognized and treated. Iron deficiency, however, is often unrecognized, despite its potential detrimental effects related to and unrelated to anemia. We investigated the interplay of anemia, iron deficiency, and patient-reported outcomes in 814 outpatient KTRs (62% male, age 56 ± 13 years) enrolled in the TransplantLines Biobank and Cohort Study (Groningen, The Netherlands). In total, 28% had iron deficiency (ie, transferrin saturation < 20% and ferritin < 100 μg/L), and 29% had anemia (World Health Organization criteria). In linear regression analyses, iron deficiency, but not anemia, was associated with more fatigue, worse concentration, lower wellbeing, more anxiety, more depressive symptoms, and lower HRQoL, independent of age, sex, estimated glomerular filtration rate, anemia, and other potential confounders. In the fully adjusted logistic regression models, iron deficiency was associated with an estimated 53% higher risk of severe fatigue, a 100% higher risk of major depressive symptoms, and a 51% higher chance of being at risk for sick leave/work disability. Clinical trials are needed to investigate the effect of iron deficiency correction on patient-reported outcomes and HRQoL in KTRs., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. M.F. Eisenga has declared receiving consultant fees from Vifor Pharma and Cablon Medical; serving on the Advisory Board for Cablon Medical and GlaxoSmithKline; and receiving speaker fees from Vifor Pharma, Pharmacosmos, and Astellas. All other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many kidney diseases are associated with proteinuria. Since proteinuria is independently associated with kidney function loss, anti-proteinuric medication, often in combination with dietary salt restriction, comprises a major cornerstone in the prevention of progressive kidney failure. Nevertheless, complete remission of proteinuria is very difficult to achieve, and most patients with persistent proteinuria slowly progress toward kidney failure. It is well-recognized that proteinuria leads to kidney inflammation and fibrosis via various mechanisms. Among others, complement activation at the apical side of the proximal tubular epithelial cells is suggested to play a crucial role as a cause of progressive loss of kidney function. However, hitherto limited attention is given to the pathophysiological role of tubular complement activation relative to glomerular complement activation. This review aims to summarize the evidence for tubular epithelial complement activation in proteinuric kidney diseases in relation to loss of kidney function., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Kidney transplantation is the best treatment for kidney failure in older patients. However, little is known regarding changes in health-related quality of life (HRQoL) from before to after transplantation and determinants of HRQoL in older kidney transplant recipients (KTR). We studied both, using data of older (≥65 years) patients waitlisted for kidney transplantation and older KTR 1 year after transplantation from the TransplantLines Biobank and Cohort Study. HRQoL was assessed using the SF-36 questionnaire. We included 145 older waitlisted patients (68% male, age 70 ± 4 years) and 115 older KTR at 1 year after transplantation (73% male, age 70 ± 4 years). Both mental (48.5 ± 8.4 versus 51.2 ± 7.7, p = 0.009) and physical (47.4 ± 8.5 versus 52.1 ± 7.2, p < 0.001) HRQoL were higher among included KTR, compared to the waitlisted patients. In paired analyses among 46 patients with HRQoL-data both before and after transplantation, there was a trend towards increased mental HRQoL (49.1 ± 8.4 to 51.6 ± 7.5, p = 0.054), and significantly increased physical HRQoL (48.1 ± 8.0 to 52.4 ± 6.7, p = 0.001) after transplantation. Among all assessed factors, the number of patient-reported immunosuppressive drug-related side effects was most strongly negatively associated with both mental and physical HRQoL. In conclusion, HRQoL is significantly higher among older KTR after kidney transplantation compared to older waitlisted patients., 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 de Boer, Knobbe, Kremer, van Munster, Nieuwenhuijs-Moeke, Pol, Bakker, Berger and Sanders.)

Background: Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant recipients (KTRs). This single-center retrospective study aimed to identify DSAm and assess their association with outcomes in a cohort of KTRs with pretransplant serum donor-specific antibodies (DSA)., Methods: We polyclonally activated pretransplant peripheral blood mononuclear cells (PBMCs) from 60 KTRs in vitro, isolated and quantified IgG from the culture supernatant using ELISA, and analyzed the HLA antibodies of eluates with single antigen bead (SAB) assays, comparing them to the donor HLA typing for potential DSAm. Biopsies from 41 KTRs were evaluated for rejection based on BANFF 2019 criteria., Results: At transplantation, a total of 37 DSAm were detected in 26 of 60 patients (43%), of which 13 (35%) were found to be undetectable in serum. No significant association was found between pretransplant DSAm and ABMR (P=0.53). Similar results were observed in a Kaplan-Meier analysis for ABMR within the first year posttransplant (P=0.29). Additionally, MFI levels of DSAm showed no significant association with ABMR (P=0.28)., Conclusion: This study suggests no significant association between DSAm and biopsy-proven clinical ABMR. Further prospective research is needed to determine whether assessing DSAm could enhance existing immunological risk assessment methods for monitoring KTRs, particularly in non-sensitized KTRs., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Altulea, van den Born, Diepstra, Bungener, Terpstra, Hepkema, Lammerts, Heeringa, Heidt, Otten, Reteig, Karahan, Berger and Sanders.)

COVID-19 is of special concern to immunocompromised individuals, including organ transplant recipients. However, the exact implications of COVID-19 for the immunocompromised host remain unclear. Existing theories regarding this matter are controversial and mainly based on clinical observations. Here, the postmortem histopathology, immunopathology, and viral presence in various tissues of a kidney transplant recipient with COVID-19 were compared to those of 2 nontransplanted patients with COVID-19 matched for age, sex, length of intensive care unit stay, and admission period in the pandemic. None of the tissues of the kidney transplant recipient demonstrated the presence of SARS-CoV-2. In lung tissues of both controls, some samples showed viral positivity with high Ct values with quantitative reverse transcription polymerase chain reaction. The lungs of the kidney transplant recipient and controls demonstrated similar pathology, consisting of acute fibrinous and organizing pneumonia with thrombosis and an inflammatory response with T cells, B cells, and macrophages. The kidney allograft and control kidneys showed a similar pattern of interstitial lymphoplasmacytic infiltration. No myocarditis could be observed in the hearts of the kidney transplant recipient and controls, although all cases contained scattered lymphoplasmacytic infiltrates in the myocardium, pericardium, and atria. The brainstems of the kidney transplant recipient and controls showed a similar pattern of lymphocytic inflammation with microgliosis. This research report highlights the possibility that, based on the results obtained from this single case, at time of death, the immune response in kidney transplant recipients with long-term antirejection immunosuppression use prior to severe illness is similar to nontransplanted deceased COVID-19 patients., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Background: Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR)., Methods: In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method. Multivariate Cox regression analyses were performed., Results: A total of 621 KTR (mean age 53 y old, 43% female) at a median of 5.2 y posttransplantation were included. Median 24-h urinary endotrophin excretion was 5.6 (3.1-13.6) µg/24h. During a median follow-up of 7.5 y, 87 KTR (14%) developed graft failure and 185 KTR (30%) died; 24-h urinary endotrophin excretion was associated with increased risk of graft failure (hazard ratio [95% confidence interva] per doubling = 1.24 [1.08-1.42]) and all-cause mortality (hazard ratio [95% confidence intervals] per doubling = 1.14 [1.03-1.25]) independent of potential confounders including plasma endotrophin concentration. Twenty-four-hour urinary protein excretion was a significant effect modifier for the association with mortality (P interaction  = 0.002). Twenty-four-hour urinary endotrophin excretion was only significantly associated with mortality in KTR with low levels of proteinuria., Conclusions: Urinary endotrophin is independently associated with an increased risk of graft failure in all KTR and mortality only in KTR with low levels of proteinuria. Further studies with different KTR populations are needed to confirm these findings., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited., Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo., Results: A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m 2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m 2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m 2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection ( P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower., Conclusions: Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We investigated whether urinary vascular non-inflammatory molecule-1 (vanin-1), a promising early-onset tubular injury marker, correlates with other established tubular injury markers and is associated with graft failure in kidney transplant recipients (KTR). We measured 24 h urinary vanin-1 excretion in 656 KTR (age 53 ± 13 years, 43% female, estimated glomerular filtration rate (eGFR) 53 ± 21 mL/min/1.73 m 2 ) who had undergone kidney transplantation ≥ 1 year. The median 24 h urinary vanin-1 excretion was 145 [51-331] pmol/24 h. 24 h urinary vanin-1 excretion correlated weakly but significantly with other tubular injury markers (ρ = 0.14, p < 0.001 with urinary liver-type fatty acid binding protein, ρ = 0.13, p = 0.001 with urinary post-translationally modified fetuin-A protein, and ρ = 0.10, p = 0.011 with plasma neutrophil gelatinase-associated lipocalin) and with eGFR (ρ = - 0.13, p = 0.001). During a median follow-up of 7.4 [4.9-8.0] years, 94 (14%) KTR developed death-censored graft failure. In multivariable Cox regression analyses, 24 h urinary vanin-1 excretion was not associated with an increased risk of death-censored graft failure (adjusted hazard ratio [95% confidence interval] = 0.96 [0.86-1.07], p = 0.5). In conclusion, our findings do not support the role of urinary vanin-1 as a biomarker of graft failure after kidney transplantation., (© 2024. The Author(s).)

Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ transplant recipients. Additionally, there is a growing interest in the role of HDL particles in immune function; therefore, assessment of both HDL concentrations and TTV load may be of interest in transplant recipients. The objective of this study was to analyze TTV loads and HDL parameters in serum samples collected at least one year post-transplantation from 656 stable outpatient kidney transplant recipients (KTRs), enrolled in the TransplantLines Food and Nutrition Cohort (Groningen, the Netherlands). Plasma HDL particles and subfractions were measured using nuclear magnetic resonance spectroscopy. Serum TTV load was measured using a quantitative real-time polymerase chain reaction. Associations between HDL parameters and TTV load were examined using univariable and multivariable linear regression. The median age was 54.6 [IQR: 44.6 to 63.1] years, 43.3% were female, the mean eGFR was 52.5 (±20.6) mL/min/1.73 m 2 and the median allograft vintage was 5.4 [IQR: 2.0 to 12.0] years. A total of 539 participants (82.2%) had a detectable TTV load with a mean TTV load of 3.04 (±1.53) log10 copies/mL, the mean total HDL particle concentration was 19.7 (±3.4) μmol/L, and the mean HDL size was 9.1 (±0.5) nm. The univariable linear regression revealed a negative association between total HDL particle concentration and TTV load (st.β = -0.17, 95% CI st.β: -0.26 to -0.09, p < 0.001). An effect modification of smoking behavior influencing the association between HDL particle concentration and TTV load was observed (P interaction = 0.024). After adjustment for age, sex, alcohol intake, hemoglobin, eGFR, donor age, allograft vintage and the use of calcineurin inhibitors, the negative association between HDL particle concentration and TTV load remained statistically significant in the non-smoking population (st.β = -0.14, 95% CI st.β: -0.23 to -0.04, p = 0.006). Furthermore, an association between small HDL particle concentration and TTV load was found (st.β = -0.12, 95% CI st.β: -0.22 to -0.02, p = 0.017). Higher HDL particle concentrations were associated with a lower TTV load in kidney transplant recipients, potentially indicative of a higher immune function. Interventional studies are needed to provide causal evidence on the effects of HDL on the immune system.

Introduction: Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs)., Methods: Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion., Results: A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses., Conclusions: Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD., Methods: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients ( n = 55), HD patients ( n = 41), non-dialysis chronic kidney disease (CKD) patients ( n = 15) and healthy controls ( n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF., Results: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients ( p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels ( p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis ( p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF ( p < 0.01)., Conclusions: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FP currently owns or owned stock in ChemoCentryx, Apellis Pharmaceuticals and Omeros Corporation. The other authors declared no conflict of interest.

Introduction: Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTRs)., Methods: KTRs with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 was quantitatively evaluated using ImageScope., Results: Sixty-seven KTRs (85% male, 46 ± 13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTRs developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034)., Conclusions: Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Fatigue and impaired health-related quality of life (HRQoL) are common among kidney transplant recipients (KTR). We hypothesized that both may partially be attributable to poor sleep., Methods: Cross-sectional and longitudinal data of KTR enrolled in the TransplantLines Biobank and Cohort Study were used. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. Individual strength (i.e. a composite of fatigue, concentration, motivation and physical activity), societal participation and HRQoL were assessed using validated questionnaires., Results: We included 872 KTR (39% female, age 56 ± 13 years) and 335 healthy controls. In total, 33% of male KTR and 49% of female KTR reported poor sleep quality, which was higher compared with male and female healthy controls (19% and 28%, respectively, P < .001 for both). In logistic regression analyses, female sex, anxiety, active smoking, low protein intake, physically inactive lifestyle, low plasma magnesium concentration, using calcineurin inhibitors, not using mTOR inhibitors and using benzodiazepine agonists were associated with poor sleep quality. In adjusted linear regression analyses, poor sleep was strongly and independently associated with lower individual strength [standardized β (st.β) = 0.59, 95% confidence interval (CI) 0.45 to 0.74, P < .001], poorer societal participation (frequency: st.β = -0.17, 95% CI -0.32 to -0.01, P = .04; restrictions: st.β = -0.36, 95% CI -0.51 to -0.21, P < .001; satisfaction: st.β = -0.44, 95% CI -0.59 to -0.28, P < .001) and lower HRQoL (physical: st.β = -0.53, 95% CI -0.68 to -0.38, P < .001; mental: st.β = -0.64, 95% CI -0.78 to -0.50, P < .001). The associations with poorer societal participation and lower HRQoL were strongly mediated by individual strength (P < .001 for all), yet the suggested direct effects of poor sleep quality on HRQoL remained significant (Pphysical = .03, Pmental = .002). Longitudinal data of 292 KTR showed that sleep quality improves after kidney transplantation in males (P < .001), but not in females (P = .9)., Conclusions: Poor sleep quality is common among KTR, and may be a potential target to improve fatigue, societal participation and HRQoL among KTR., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10 -65 ) and mental HRQoL (R = -0.14, P = 1.3 × 10 -3 ). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R 2  = 0.58%, FDR = 5.43 × 10 -4 and R 2  = 0.37%, FDR = 1.38 × 10 -3 , respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders., (© 2023. The Author(s).)

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney., Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125 I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson's correlation coefficient and linear regression were used to assess relations between parameters., Results: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 μm 2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.β = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.β = 0.31, p = 0.01) and at five years (St.β = 0.30, p = 0.01) after donation, independent of age., Conclusions: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors., (© 2023. The Author(s).)

Rationale & Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population., Study Design: Cross-sectional study., Setting & Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study., Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use., Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire., Analytical Approach: Logistic and linear regression., Results: We included 937 kidney transplant recipients (mean age 56±13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P<0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P<0.001), lower physical HRQoL (regression coefficient-8.54, 95% CI, -11.54 to-5.54, P<0.001), and lower mental HRQoL (regression coefficient-4.66, 95% CI, -7.15 to-2.17, P<0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity., Limitations: Residual confounding and inability to assess causal relationships., Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted., Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Kidney transplant candidates (KTCs) need to be in optimal physical and psychological condition prior to surgery. However, KTCs often experience compromised functional capacity which can be characterised as frailty. Prehabilitation, the enhancement of a person's functional capacity, may be an effective intervention to improve the health status of KTCs. The PREhabilitation of CAndidates for REnal Transplantation (PreCareTx) study aims to examine the effectiveness of a multimodal prehabilitation programme on the health status of KTCs, and to explore the potential of implementation of prehabilitation in daily clinical practice., Methods and Analysis: This study uses a single centre, effectiveness-implementation hybrid type I study design, comprised of a randomised controlled trial and a mixed-methods study. Adult patients who are currently on the transplant waiting list or are waitlisted during the study period, at a university medical centre in The Netherlands, will be randomly assigned to either prehabilitation (n=64) or care as usual (n=64) groups. The prehabilitation group will undergo a 12-week home-based, tailored prehabilitation programme consisting of physical and/or nutritional and/or psychosocial interventions depending on the participant's deficits. This programme will be followed by a 12-week maintenance programme in order to enhance the incorporation of the interventions into daily life. The primary endpoint of this study is a change in frailty status as a proxy for health status. Secondary endpoints include changes in physical fitness, nutritional status, psychological well-being, quality of life and clinical outcomes. Tertiary endpoints include the safety, feasibility and acceptability of the prehabilitation programme, and the barriers and facilitators for further implementation., Ethics and Dissemination: Medical ethical approval was granted by the Medical Ethics Committee Groningen, Netherlands (M22.421). Written informed consent will be obtained from all participants. The results will be disseminated at international conferences and in peer-reviewed journals., Trial Registration Number: ClinicalTrials.gov, NCT05489432., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Normothermic machine perfusion (NMP) is a promising modality for marginal donor kidneys. However, little is known about the effects of NMP on causing endothelial glycocalyx (eGC) injury. This study aims to evaluate the effects of NMP on eGC injury in marginal donor kidneys and whether this is affected by perfusion pressures and hematocrits., Methods: Porcine slaughterhouse kidneys (n = 6/group) underwent 35 min of warm ischemia. Thereafter, the kidneys were preserved with oxygenated hypothermic machine perfusion for 3 h. Subsequently, 4 h of NMP was applied using pressure-controlled perfusion with an autologous blood-based solution containing either 12%, 24%, or 36% hematocrit. Pressures of 55, 75, and 95 mm Hg were applied in the 24% group. Perfusate, urine, and biopsy samples were collected to determine both injury and functional parameters., Results: During NMP, hyaluronan levels in the perfusate increased significantly ( P < 0.0001). In addition, the positivity of glyco-stained glycocalyx decreased significantly over time, both in the glomeruli ( P = 0.024) and peritubular capillaries ( P = 0.003). The number of endothelial cells did not change during NMP ( P = 0.157), whereas glomerular endothelial expression of vascular endothelial growth factor receptor-2 decreased significantly ( P < 0.001). Microthrombi formation was significantly increased after NMP. The use of different pressures and hematocrits did not affect functional parameters during perfusion., Conclusions: NMP is accompanied with eGC and vascular endothelial growth factor receptor-2 loss, without significant loss of endothelial cells. eGC loss was not affected by the different pressures and hematocrits used. It remains unclear whether endothelial injury during NMP has harmful consequences for the transplanted kidney., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Neurocognitive impairment is common in kidney transplant recipients (KTRs). Adequate brain functioning requires energy and neurotransmitter activity, for which iron is essential. We aimed to investigate iron deficiency (ID) as a potentially modifiable risk factor for cognitive impairment in KTRs., Methods: We analyzed stable KTRs participating in the TransplantLines Biobank and Cohort study. Participants underwent neuropsychological tests for memory, mental speed, and attention and executive functioning. ID was defined as ferritin <100 µg/mL or 100-299 µg/mL with transferrin saturation (TSAT) ≤20%. Associations between iron status and norm scores of neurocognitive outcomes, corrected for age, sex and education, were assessed using multivariable linear regression analyses adjusted for potential confounders including hemoglobin., Results: We included 166 KTRs [median (IQR) age 57 (45-65) years, 59% male, estimated glomerular filtration rate 51±18 mL/min/1.73 m2]. Time since transplantation was 5.8 (1.0-12.0) years. Prevalence of ID was 65%. ID was independently associated with lower scores for mental speed (std.β = -0.19, P = .02) and attention and executive functioning (std.β = -0.19, P = .02), and tended to be associated with worse memory (std.β = -0.16, P = .07). Lower plasma ferritin levels were associated with worse memory (std.β = 0.23, P = .007), mental speed (std.β = 0.34, P < .001), and attention and executive functioning (std.β = 0.30, P = .001). Lower TSAT was associated with worse memory (std.β = 0.19, P = .04) and mental speed (std.β = 0.27, P = .003), and tended to be associated with worse attention and executive functioning (std.β = 0.16, P = .08)., Conclusions: Iron-deficient KTRs performed worse on neurocognitive tasks measuring memory, mental speed, and attention and executive functioning. These findings set the stage for prospective studies addressing whether ID correction restores cognitive function after kidney transplantation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)