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Search Results (582)

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11 pages, 594 KB  
Systematic Review
Outcomes and Complications of Total Joint Arthroplasty in Heart Transplant Recipients: A Systematic Review
by Alexandros Koskiniotis, George A. Komnos, Antonios Koutalos, Michael Hantes, Theofilos Karachalios, Sokratis Varitimidis and Nikolaos Stefanou
J. Clin. Med. 2026, 15(17), 6794; https://doi.org/10.3390/jcm15176794 - 1 Sep 2026
Viewed by 125
Abstract
Background: Heart transplantation has evolved into a life-saving intervention for thousands of patients with end-stage disease worldwide. Advances in surgical techniques and immunotherapy have increased life expectancy in this specific patient group, resulting in the emergence of degenerative diseases such as osteoarthritis. [...] Read more.
Background: Heart transplantation has evolved into a life-saving intervention for thousands of patients with end-stage disease worldwide. Advances in surgical techniques and immunotherapy have increased life expectancy in this specific patient group, resulting in the emergence of degenerative diseases such as osteoarthritis. Concurrently, due to the frequent administration of corticosteroids to transplant recipients, the rates of joint osteonecrosis remain high. This review aims to evaluate the final functional outcomes as well as the complications of patients with a history of heart transplantation who underwent total hip, knee, or shoulder arthroplasty. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. The primary objective of the study was the improvement of various functional scores at the final clinical follow-up, as well as the recording of postoperative complication rates. Results: A total of 19 retrospective studies were included in the review, including small case series. Among the studies specifically evaluating functional outcomes, patients demonstrated statistically significant improvement in final clinical scores and quality of life. However, regarding complication rates, 12 out of the 19 articles identified a higher ratio compared to the general population, involving either systemic (e.g., renal failure), musculoskeletal (periprosthetic fracture, infection), or cardiac-related adverse events concerning the graft. Conclusions: According to the data analyzed in this systematic analysis, total arthroplasty of major joints demonstrates consistent potential to significantly improve the daily life and functional status of transplant patients. However, evidence regarding overall safety remains heterogeneous. Full article
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9 pages, 200 KB  
Brief Report
Association Between the Implementation of Shared Decision-Making and Clinical Characteristics of Living-Donor Kidney Transplantation
by Akito Mochizuki, Kazuhiro Tada, Sho Shimamoto, Koji Takahashi, Kenji Ito, Yoko Yokoyama, Masahiro Tachibana, Nobuyuki Nakamura, Nobuhiro Haga and Kosuke Masutani
Healthcare 2026, 14(17), 2774; https://doi.org/10.3390/healthcare14172774 - 1 Sep 2026
Viewed by 135
Abstract
Background/Objectives: Shared decision-making (SDM), which incorporates patients’ values and preferences, may support patient-centered selection of renal replacement therapy, but its association with the clinical characteristics of living-donor kidney transplantation (LDKT) remains unclear. This study aimed to evaluate the association between SDM implementation and [...] Read more.
Background/Objectives: Shared decision-making (SDM), which incorporates patients’ values and preferences, may support patient-centered selection of renal replacement therapy, but its association with the clinical characteristics of living-donor kidney transplantation (LDKT) remains unclear. This study aimed to evaluate the association between SDM implementation and the clinical characteristics of LDKT. Methods: A specialized SDM outpatient clinic was established at our institution in 2019. We retrospectively analyzed 65 patients who underwent LDKT at a single center between 2010 and 2025, comparing a pre-SDM group (2010–2018, n = 25) with a post-SDM group (2019–2025, n = 40). Results: Recipient characteristics were similar between groups, whereas donors were older after SDM implementation (62.0 [52.3–68.0] vs. 55.0 [44.5–60.0] years; p = 0.01). ABO-incompatible transplantation (37.5% vs. 4.0%; p = 0.003) and preformed donor-specific antibody-positive transplantation (20.0% vs. 0%; p = 0.02) were more frequent in the post-SDM group. The proportion of preemptive kidney transplantation (PEKT) was similar; however, among PEKT recipients, estimated glomerular filtration rate was higher at initial evaluation and admission, and preoperative dialysis was numerically less frequent in the post-SDM group (20.0% vs. 54.5%; p = 0.106). Conclusions: Implementation of the SDM clinic was associated with a higher frequency of immunologically complex LDKT and better-preserved kidney function at initial transplant evaluation and admission among PEKT recipients. These associations should be interpreted cautiously given potential secular changes in transplant practice. Full article
(This article belongs to the Section Clinical Care)
16 pages, 879 KB  
Review
Clinical Evolution, Outcomes, and Emerging Preservation Technologies in Pancreas and Islet Transplantation
by Maria Irene Bellini and Vassilios Papalois
J. Clin. Med. 2026, 15(17), 6774; https://doi.org/10.3390/jcm15176774 - 31 Aug 2026
Viewed by 246
Abstract
Historically regarded as competitive modalities, pancreas and islet transplantation are increasingly recognized as complementary approaches to beta-cell replacement therapy. While whole-organ pancreas transplantation remains the established gold standard, islet transplantation has transitioned into an effective clinical alternative for selected cohorts of patients suffering [...] Read more.
Historically regarded as competitive modalities, pancreas and islet transplantation are increasingly recognized as complementary approaches to beta-cell replacement therapy. While whole-organ pancreas transplantation remains the established gold standard, islet transplantation has transitioned into an effective clinical alternative for selected cohorts of patients suffering from type 1 diabetes. This review provides a comprehensive evaluation of the clinical evolution characterizing these therapeutic modalities, tracing the shift from static cold storage (SCS) toward innovative dynamic preservation technologies, and exploring potential markers for predicting clinical outcomes. A focus on immunosuppression in islet transplantation is provided, emphasizing precise, tolerance-inducing strategies and investigating costimulation blockade, regulatory T-cell (Treg)-based therapies, and biomaterial-enabled local immunoprotection, with the aim of facilitating long-term graft survival while mitigating the metabolic and renal toxicities secondary to chronic calcineurin inhibitor exposure. Current evidence related to the transition from conventional SCS to advanced perfusion platforms, namely hypothermic machine perfusion (HMP), oxygenated hypothermic perfusion (HOPE), normothermic ex vivo perfusion (NEVP), and normothermic regional perfusion (NRP) is examined: the literature suggests that dynamic pancreas preservation platforms may improve metabolic recovery and some islet isolation outcomes; however, evidence that HOPE specifically reduces ischemia–reperfusion injury and consistently increases islet yield in the pancreas remains limited. Although normothermic perfusion provides significant utility for real-time viability assessment and graft reconditioning, its widespread clinical implementation remains constrained by technical impediments, notably interstitial edema. Ultimately, preservation efficacy is conceptualized not merely as a discrete preservation option, but as a multidimensional construct integrating biological integrity, graft usability, and recipient clinical outcomes. Full article
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23 pages, 1953 KB  
Article
Short-Term Silymarin Supplementation After Kidney Transplantation Is Associated with Reduced Early Albuminuria: A Prospective Cohort Study
by Matej Vnučák, Karol Graňák, Patrícia Kleinová, Tímea Jusková, Andrej Kollár, Katarína Ševčíková and Ivana Dedinská
J. Clin. Med. 2026, 15(17), 6694; https://doi.org/10.3390/jcm15176694 - 28 Aug 2026
Viewed by 149
Abstract
Background: Early post-transplant albuminuria is associated with adverse graft and cardiovascular outcomes and may reflect ischemia–reperfusion injury-induced damage to the glomerular filtration barrier. However, evidence for safe adjunctive interventions targeting these early pathophysiological processes remains limited. Methods: In this single-center prospective cohort study [...] Read more.
Background: Early post-transplant albuminuria is associated with adverse graft and cardiovascular outcomes and may reflect ischemia–reperfusion injury-induced damage to the glomerular filtration barrier. However, evidence for safe adjunctive interventions targeting these early pathophysiological processes remains limited. Methods: In this single-center prospective cohort study with historical controls, adult kidney transplant recipients transplanted between January 2020 and September 2022 served as controls, while consecutive recipients transplanted from October 2022 onward received adjunctive silymarin (900 mg/day for 30 days) in addition to standard immunosuppression. The principal renal outcome was UACR assessed during the first 3 months post-transplant. A ≥25% reduction in UACR between Months 1 and 3 was additionally evaluated as an exploratory responder outcome. Secondary outcomes included estimated glomerular filtration rate (eGFR), lipid profile parameters, tacrolimus exposure, and safety. Results: A total of 136 patients (78 silymarin-treated and 58 controls) were included. UACR was consistently lower in the silymarin group at months 1–3. In multivariable analysis, silymarin treatment was independently associated with lower UACR at month 3. In an exploratory responder analysis, a ≥25% reduction in UACR between Months 1 and 3 occurred more frequently in silymarin-treated patients (OR 3.28, 95% CI 1.38–7.79; p = 0.007). eGFR trajectories were similar between groups. No consistent independent effects on lipid parameters were observed after adjustment. Tacrolimus exposure and adverse event rates were comparable between groups. Conclusions: Short-term silymarin exposure initiated early after kidney transplantation was associated with lower UACR during the first three post-transplant months. These findings support a potential targeted effect on early glomerular injury and suggest that silymarin may represent a safe adjunctive strategy to modulate early post-transplant risk. Full article
(This article belongs to the Section Nephrology & Urology)
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17 pages, 4269 KB  
Article
Everolimus-Involving Immunosuppression Attenuates Renal Interstitial Fibrosis Through Modulation of Mammalian Target of Rapamycin-Related Signal Transduction
by Takuro Saito, Mitsuru Saito, Ryohei Yamamoto, Ryuichiro Sagehashi, Yu Aoyama, Mizuki Mori, Chika Kajiwara, Kengo Furihata, Hideaki Kagaya, Hironobu Yagishita, Nobuhiro Fujiyama, Soki Kashima, Kazuyuki Numakura, Shintaro Narita, Masafumi Kikuchi, Masatomo Miura and Tomonori Habuchi
Int. J. Mol. Sci. 2026, 27(17), 7634; https://doi.org/10.3390/ijms27177634 - 26 Aug 2026
Viewed by 179
Abstract
Chronic allograft dysfunction, driven by interstitial fibrosis and tubular atrophy, remains a major cause of long-term renal allograft loss. Everolimus (EVR), a mammalian target of rapamycin (mTOR) inhibitor, may reduce fibrosis through antifibrotic effects and calcineurin inhibitor minimization. This study aimed to evaluate [...] Read more.
Chronic allograft dysfunction, driven by interstitial fibrosis and tubular atrophy, remains a major cause of long-term renal allograft loss. Everolimus (EVR), a mammalian target of rapamycin (mTOR) inhibitor, may reduce fibrosis through antifibrotic effects and calcineurin inhibitor minimization. This study aimed to evaluate the impact of EVR-involving immunosuppression on renal allograft fibrosis and to identify predictors of fibrotic progression. A total of 104 living-donor kidney transplant recipients transplanted between 2011 and 2017 were retrospectively analyzed (EVR, n = 61; non-EVR, n = 43). Interstitial fibrosis was quantified in protocol biopsies using digital image analysis. Phosphorylation of the mTOR-signaling proteins p70 ribosomal S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 was assessed using a semiquantitative immunoreactive score. Multivariable regression analyses identified independent predictors of fibrotic progression. Cytomegalovirus infection was less frequent in the EVR group, whereas acute rejection, graft function, and graft survival were comparable between groups. At 1-year posttransplantation, interstitial fibrosis was significantly lower in the EVR group. EVR significantly suppressed p-4EBP1 phosphorylation and effectively modulated the mTOR-signaling pathway. Multivariable analysis identified the absence of EVR therapy as an independent predictor of accelerated fibrosis. EVR-involving immunosuppression attenuated renal interstitial fibrosis, likely through suppression of mTOR-signaling. Full article
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13 pages, 681 KB  
Review
Hepatitis C in Chronic Kidney Disease After the DAA Revolution: Clinical Decisions, Transplantation, and Implementation Challenges
by Mostafa Mohrag, Ali Someili, Erwa Elmakki and Mohammed Abdulrasak
J. Clin. Med. 2026, 15(17), 6504; https://doi.org/10.3390/jcm15176504 - 22 Aug 2026
Viewed by 259
Abstract
Direct-acting antiviral (DAA) therapy has dramatically transformed the management of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). Severe renal impairment and dialysis dependence are no longer considered major barriers to virologic cure. The main difficulties have shifted toward efficient diagnosis, [...] Read more.
Direct-acting antiviral (DAA) therapy has dramatically transformed the management of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). Severe renal impairment and dialysis dependence are no longer considered major barriers to virologic cure. The main difficulties have shifted toward efficient diagnosis, choosing the regimen in the presence of cirrhosis and drug interactions, coordinating treatment with kidney transplantation, managing HCV-associated immune-complex kidney disease, and providing treatment in dialysis and resource-limited settings. This narrative review aims to discuss these issues in a decision-oriented manner, using verified guidelines, systematic reviews, important clinical trials, transplant cohorts, and studies of cryoglobulinemic disease, while explicitly comparing the strength and consistency of the underlying evidence and highlighting areas of genuine clinical uncertainty. Present evidence supports using the recommended DAA regimens without renal dose adjustment, while ribavirin needs dose modification when kidney function is reduced and can result in hemolytic anemia. Kidneys from HCV-viremic donors can be transplanted to recipients without HCV infection when proper informed consent, rapid access to DAA treatment, and organized post-transplant monitoring are available, although the minimum effective duration of peri-transplant antiviral prophylaxis remains unresolved. Antiviral therapy is the first-line treatment for HCV-associated glomerular disease, while rituximab-based immunosuppression is largely reserved for severe, rapidly progressive, or persistent cryoglobulinemic vasculitis. Future progress will depend less on proving antiviral efficacy and more on closing the gaps between screening, confirmatory testing, starting treatment, transplantation pathways, and long-term follow-up, gaps that stem from inequities in diagnostic infrastructure, drug reimbursement, and healthcare-system organization as much as from any remaining biomedical uncertainty. Full article
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13 pages, 277 KB  
Article
Integrated Serum and Urinary Metabolomics Reveal Distinct Signatures of Kidney Graft Function—A Single-Center Cohort Study
by Cezar Valeriu Băluță, Lucian Siriteanu, Ionuț Nistor, Luminița Voroneanu, Simona Mihaela Hogas, Andreea Covic, Călin Namolovan, Raluca Erika Irimie Băluță, Radu Gavril, Calin Deleanu, Alina Nicolescu, Mehmet Kanbay and Adrian Covic
Biomedicines 2026, 14(8), 1875; https://doi.org/10.3390/biomedicines14081875 - 21 Aug 2026
Viewed by 397
Abstract
Background/Objectives: Kidney transplantation remains the gold standard treatment of end-stage kidney disease; however, its recipients exhibit mixed clinical trajectories, with variable renal function and proteinuria evolution over time. Currently used methods to screen these changes are associated with possible adverse effects and [...] Read more.
Background/Objectives: Kidney transplantation remains the gold standard treatment of end-stage kidney disease; however, its recipients exhibit mixed clinical trajectories, with variable renal function and proteinuria evolution over time. Currently used methods to screen these changes are associated with possible adverse effects and limitations. Methods: In this single-center cohort study, 174 adult kidney transplant recipients were enrolled between January 2024 and January 2025 and followed for 12 months. Patients underwent serum and urinary metabolomic profiling using nuclear magnetic resonance (NMR) spectroscopy. Furthermore, clinical and biological data were collected, allowing for assessment of changes in renal function and proteinuria, with patient stratification based on outcome trends. Results: Serum metabolomic profiles were linked to renal outcomes. For ΔeGFR, valine differed between patients with positive and negative trajectories, while GlycA, GlycB and Glyc/SPC were associated with ΔeGFR in adjusted models. For Δproteinuria, GlycA, VLDL particles and triglycerides showed correlations, while glucose differed between patients with improving and worsening proteinuria. In adjusted models, isoleucine, alanine, GlycA and Glyc/SPC were associated with Δproteinuria. Urinary metabolomic profiles showed fewer associations. Dimethylamine and urinary creatinine were associated with ΔeGFR in adjusted models, while acetic acid differed between proteinuria groups. No urinary metabolite was associated with Δproteinuria after adjustment. Conclusions: Overall, metabolomic changes were connected with renal outcomes in kidney transplant patients, with distinct but partially overlapping patterns for ΔGFR and Δproteinuria. Serum findings were more consistent, while urinary associations were more limited. Further longitudinal and externally validated studies are required to confirm these observations and explore the potential of this metabolomic approach in the search for novel biomarkers. Full article
31 pages, 1865 KB  
Article
Topical Magnesium Orotate Lipogel in Kidney Transplant Recipients with Persistent Hypomagnesemia: Formulation Development and Pilot Clinical Study
by Corina Moisa, Florin Bănică, Ioana Adela Rațiu, Octavia Gligor, Laura Grațiela Vicaș, Cristian Adrian Rațiu, Mădălin Florin Ganea, Csaba Nagy, Anamaria Ratiu, Edy Hagi Islai and Mariana Ganea
Nutrients 2026, 18(16), 2740; https://doi.org/10.3390/nu18162740 - 21 Aug 2026
Viewed by 423
Abstract
Background: In solid-organ transplant recipients, hypomagnesemia is a frequent and persistent complication, predominantly related to long-term use of calcineurin inhibitors. Oral magnesium supplementation is often ineffective due to poor adherence, gastrointestinal adverse effects, and high treatment costs. Objectives: This pilot study [...] Read more.
Background: In solid-organ transplant recipients, hypomagnesemia is a frequent and persistent complication, predominantly related to long-term use of calcineurin inhibitors. Oral magnesium supplementation is often ineffective due to poor adherence, gastrointestinal adverse effects, and high treatment costs. Objectives: This pilot study aimed to (i) develop a topical magnesium formulation for use in renal transplant recipients with persistent hypomagnesemia; (ii) evaluate the influence of formulation excipients on magnesium release from pharmaceutical preparations; and (iii) preliminarily assess the clinical outcomes, functional parameters, patient satisfaction, and tolerability associated with topical magnesium lipogel use in renal transplant recipients with persistent hypomagnesemia. Materials and Methods: Three lipogel formulations containing magnesium orotate, citrate, or sulfate were prepared and characterized in terms of organoleptic properties, pH, colloidal stability, and rheological behavior. In vitro magnesium release was evaluated using Franz diffusion cells. The formulation demonstrating the most favorable release profile, magnesium orotate lipogel, was administered twice daily for two months to 21 renal transplant recipients with persistent hypomagnesemia who had shown inadequate response, intolerance, or non-adherence to oral magnesium supplementation. Laboratory parameters were assessed at baseline and after treatment. Patient satisfaction was evaluated using the Lübeck questionnaire, while physical activity and exercise capacity were assessed using the International Physical Activity Questionnaire (IPAQ) and metabolic equivalent task (MET) calculations. Results: Franz cell studies demonstrated superior magnesium release from the magnesium orotate lipogel compared with the other formulations. After two months, serum magnesium levels were higher than baseline (1.554 ± 0.124 vs. 1.448 ± 0.111 mg/dL, p < 0.001), although they remained below the normal reference range. No significant changes were observed in eGFR or hsCRP. Moderate-intensity physical activity increased significantly (310.475 ± 92.505 vs. 279.286 ± 89.907 MET-min/week, p < 0.001), while vigorous-intensity activity did not change significantly. No relevant adverse effects were reported. Patient satisfaction was high across all evaluated domains, including practicability (86.6%), efficacy (96.4%), tolerability (97.1%), and trust in medical professionals (97.6%). Conclusions: In this pilot study, topical magnesium orotate lipogel was well tolerated and accepted by renal transplant recipients with persistent hypomagnesemia. Serum magnesium levels and moderate physical activity improved over the two-month observation period, although magnesium levels remained below the normal range. These preliminary findings warrant confirmation in larger, randomized, placebo-controlled studies. Full article
(This article belongs to the Special Issue Magnesium in Aging, Health and Diseases)
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22 pages, 1326 KB  
Review
Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification—A Narrative Review
by Caterina Nela Dumitru, Teodora Marcu, Alina Oana Dumitru, Simona Steliana Tudor, Ionela Daniela Ferțu, Alina-Mihaela Elisei and Larisa Goroftei
Pharmaceuticals 2026, 19(8), 1313; https://doi.org/10.3390/ph19081313 - 20 Aug 2026
Viewed by 2923
Abstract
Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far [...] Read more.
Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement–drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era. Full article
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13 pages, 681 KB  
Article
Parathyroid Hormone Levels at Transplant and Outcomes in Renal Transplant Recipients: A Single-Center Retrospective Study
by Ruyan Zhang, Justin H. Wong, Linda L. Wong and Lung-Yi Lee
Transplantology 2026, 7(3), 19; https://doi.org/10.3390/transplantology7030019 - 18 Aug 2026
Viewed by 240
Abstract
Background: Patients with end-stage kidney disease commonly develop hyperparathyroidism, which may impair muscle strength and physical function. Elevated parathyroid hormone (PTH) levels have been associated with weakness and poor Timed Up and Go (TUG) test performance. We hypothesized that elevated PTH at kidney [...] Read more.
Background: Patients with end-stage kidney disease commonly develop hyperparathyroidism, which may impair muscle strength and physical function. Elevated parathyroid hormone (PTH) levels have been associated with weakness and poor Timed Up and Go (TUG) test performance. We hypothesized that elevated PTH at kidney transplantation would correlate with worse TUG performance and poorer post-transplant outcomes. Methods: We performed a retrospective cohort study of 226 kidney transplant recipients (2015–2023) at a single transplant center with documented TUG testing and PTH levels. Patients were divided into normal PTH (≤600 pg/mL, nPTH) and high PTH (>600 pg/mL, hPTH) groups. Demographics, clinical characteristics, and transplant outcomes, including graft and patient survival, were analyzed. Results: The hPTH group (n = 16) was younger than the nPTH group (41.8 vs. 55.4 years, p < 0.001) and more likely to have English as a second language (62.5% vs. 35.6%, p = 0.032). They also had lower estimated post-transplant survival scores (29.3 vs. 52.0, p = 0.003) and higher rates of hyperphosphatemia (18.8% vs. 4.3%, p = 0.044). TUG pass rates, acute rejection, delayed graft function, and patient survival were similar between groups. However, the hPTH group demonstrated shorter mean graft survival (6.6 vs. 7.7 years, p = 0.022). On multivariable Cox regression, elevated PTH at transplantation remained independently associated with graft failure (adjusted hazard ratio 20.6, 95% CI 1.91–222). Conclusions: Elevated PTH at transplant was associated with poorer graft survival despite similar rejection rates and patient survival. Although not directly measured in this study, high PTH may reflect increased medical complexity or adherence-related challenges. Full article
(This article belongs to the Section Solid Organ Transplantation)
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13 pages, 802 KB  
Article
Real-World Effectiveness and Renal Safety of Foscarnet for CMV Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation
by Leylagül Kaynar, Ibrahim Abdi Ali, Mahmoud Alrais, Amir Hossein Abedi, Süreyya Yiğit Kaya, Olgu Erkin Çınar, Hüseyin Saffet Beköz and Senem Maral
J. Clin. Med. 2026, 15(16), 6365; https://doi.org/10.3390/jcm15166365 - 18 Aug 2026
Viewed by 308
Abstract
Background/Objectives: Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir is used to prevent infections, but it is not available in many countries. Ganciclovir and valganciclovir carry a risk of bone [...] Read more.
Background/Objectives: Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir is used to prevent infections, but it is not available in many countries. Ganciclovir and valganciclovir carry a risk of bone marrow suppression. Foscarnet is frequently used as a bone marrow-sparing alternative; however, its clinical utility is constrained by nephrotoxicity. In this study, we aimed to evaluate the efficacy and renal safety of foscarnet and to identify factors associated with acute kidney injury (AKI) occurring during foscarnet treatment. Methods: This real-world, retrospective, single-center cohort study included 40 adult allo-HCT recipients treated with foscarnet for CMV reactivation between May 2022 and February 2025. Results: CMV polymerase chain reaction (PCR) negativity was achieved in 90% of patients, with a median time to PCR negativity of 10 (4–28) days. AKI occurred in 42.5% of patients, and 12.5% required hemodialysis. Foscarnet treatment was associated with a significant increase in serum creatinine levels and significant reductions in potassium, calcium, and magnesium concentrations (p < 0.05 for all). In univariable logistic regression analysis, myeloablative conditioning was associated with higher odds of AKI (OR 10.29, 95% CI 1.15–91.63; p = 0.037), while male sex showed numerically higher odds that did not reach conventional statistical significance (OR 4.28, 95% CI 0.96–19.01; p = 0.056). Conclusions: Among allo-HCT recipients treated with foscarnet, virological clearance was frequently observed, while AKI and electrolyte disturbances were common. These findings suggest that close renal and electrolyte monitoring may be warranted. However, given the retrospective, single-center design, small sample size, and absence of a comparator group, the findings should be interpreted cautiously and confirmed in larger prospective comparative studies. Full article
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18 pages, 597 KB  
Review
Pregnancy Outcomes After Belatacept Exposure in Solid Organ Transplant Recipients: A Scoping Review
by Ibrahim Tawhari, Manal Alotaibi, Hany El Hennawy, Fatmah Yamani, Muath Alqahtani, Khalid Asiri and Mohammed Tawhari
Healthcare 2026, 14(16), 2561; https://doi.org/10.3390/healthcare14162561 - 16 Aug 2026
Viewed by 309
Abstract
Background: Pregnancy after solid organ transplantation carries increased maternal and fetal risks, compounded by the teratogenicity, nephrotoxicity, and metabolic effects of available immunosuppressive agents. Belatacept, a calcineurin inhibitor-sparing T-cell costimulation blocker with favorable renal and metabolic profiles, has emerged as an alternative; [...] Read more.
Background: Pregnancy after solid organ transplantation carries increased maternal and fetal risks, compounded by the teratogenicity, nephrotoxicity, and metabolic effects of available immunosuppressive agents. Belatacept, a calcineurin inhibitor-sparing T-cell costimulation blocker with favorable renal and metabolic profiles, has emerged as an alternative; however, evidence regarding its safety during pregnancy remains scarce. Methods: A scoping review was conducted per PRISMA-ScR recommendations. PubMed, Google Scholar, Web of Science, Scopus, and the Cochrane Library were searched (January 2015–March 2025), supplemented by citation searching, for studies reporting pregnancy outcomes in solid organ transplant recipients receiving belatacept. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Results: Three studies (one case series and two case reports) encompassing 21 pregnancies among 15 recipients were included, predominantly in kidney transplant recipients; several recipients contributed more than one pregnancy, so pregnancy-level outcomes are not statistically independent. Sixteen pregnancies resulted in live birth and five ended in miscarriage, at least four of which occurred in pregnancies with periconception mycophenolate exposure. No congenital malformations were reported among live-born infants, although the number of exposures is far too small to characterize teratogenic risk. Stable allograft function was reported in 14 of 19 pregnancies with available follow-up, with no rejection episodes during belatacept exposure. Maternal complications included preeclampsia (8 of 16 in the case series), gestational diabetes, cytomegalovirus reactivation, and acute kidney injury. Low birth weight (<2500 g) was reported in all live births, predominantly in the context of preterm delivery. Conclusions: The published cases have not identified congenital malformations to date, but the number of documented exposures is far too small to characterize teratogenic risk, and the overall certainty of evidence is very low. Because no comparative studies were available, maternal and neonatal outcomes cannot be assumed equivalent to those of conventional immunosuppression. Belatacept cannot be recommended for routine use during pregnancy; clinical decisions must remain individualized, and preconception counseling and prospective multicenter registries are urgently needed. Full article
(This article belongs to the Special Issue Focus on Maternal, Pregnancy and Child Health: Second Edition)
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21 pages, 360 KB  
Article
Cardiac Comorbidity Burden and Post-Liver Transplant Outcomes: A Propensity-Matched Multicenter Analysis
by Noor Albusta, Sara Isa, Ali Bosta and Rehab Almarzooq
J. Clin. Med. 2026, 15(16), 6260; https://doi.org/10.3390/jcm15166260 - 13 Aug 2026
Viewed by 259
Abstract
Background/Objectives: Cardiac comorbidities are increasingly common among liver transplant candidates, particularly those with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis. Although the Liver Transplant Comorbidity Index identifies coronary artery disease (CAD) as a predictor of post-transplant mortality, the impact of overall cardiac comorbidity burden on [...] Read more.
Background/Objectives: Cardiac comorbidities are increasingly common among liver transplant candidates, particularly those with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis. Although the Liver Transplant Comorbidity Index identifies coronary artery disease (CAD) as a predictor of post-transplant mortality, the impact of overall cardiac comorbidity burden on early outcomes after liver transplantation remains unclear. We evaluated the association between pre-transplant cardiac comorbidities and early post-transplant outcomes, with emphasis on MASH-related cirrhosis. Methods: We performed a retrospective cohort study using the TriNetX US Collaborative Research Network. Adults undergoing first-time isolated liver transplantation through May 2026 were included. Pre-transplant CAD, heart failure (HF), and atrial fibrillation (AF) documented within 12 months before transplantation were identified using ICD-10-CM codes. Patients were categorized by cardiac comorbidity burden (0–3 conditions). Recipients with any cardiac comorbidity underwent 1:1 propensity score matching to those without cardiac disease using 16 baseline demographic, clinical, and laboratory variables, including MELD-Na. The estimand was the average treatment effect in the treated patients. Primary outcomes comprised 30- and 90-day all-cause mortality. Secondary outcomes included a prespecified restricted major adverse cardiac event (MACE) composite, limited to hard endpoints (death, myocardial infarction, cardiac arrest, ischemic stroke), and a broader composite, i.e., acute kidney injury, prolonged mechanical ventilation, vasopressor requirement, renal replacement therapy, ICU and hospital length of stay, and 90-day readmission. Results: Among 5124 recipients, 986 (19.2%) exhibited at least one cardiac comorbidity. After matching, 974 patients remained in each group. Pre-transplant cardiac comorbidity was associated with higher 30- and 90-day mortality and increased risks of all secondary outcomes. The association with MACE persisted but was attenuated when restricted to hard endpoints (90-day RR 1.55; 95% CI 1.19–2.03) when compared with the broad composite (RR 1.75; 95% CI 1.40–2.18). MASH recipients with cardiac comorbidities experienced numerically higher event rates than did non-MASH recipients, but interaction estimates were imprecise and non-significant. In separate matched analyses, AF was most strongly associated with MACE, whereas CAD showed the strongest association with mortality. Conclusions: Pre-transplant cardiac comorbidity burden is associated with worse early post-transplant outcomes. Although MASH-cirrhosis recipients experienced numerically higher event rates, exploratory subgroup analyses did not demonstrate statistically significant differences from the non-MASH recipients. These findings may help refine cardiac risk prediction and perioperative planning, but they do not establish that intensified cardiac risk stratification or perioperative optimization improve outcomes. Prospective studies incorporating detailed cardiac, donor, operative, frailty, and medication data are needed to validate these associations and determine whether targeted risk-stratification and perioperative strategies can improve post-transplant outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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15 pages, 1569 KB  
Article
Divergent Cellular and Humoral Immunity to BK Polyomavirus in Healthy Adults and Renal Transplant Recipients Based on Blood and Urine Samples: Implications for Immune-Guided Monitoring
by Deema Ibrahim Fallatah and Steve Christmas
Biomedicines 2026, 14(8), 1820; https://doi.org/10.3390/biomedicines14081820 - 13 Aug 2026
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Abstract
Background/Objectives: BK polyomavirus (BKPyV) establishes lifelong, asymptomatic persistence but frequently reactivates in renal transplant recipients, contributing to significant post-transplant morbidity. Although humoral responses are routinely monitored, the role of cellular immunity in viral control remains incompletely characterized. This study aimed to characterize [...] Read more.
Background/Objectives: BK polyomavirus (BKPyV) establishes lifelong, asymptomatic persistence but frequently reactivates in renal transplant recipients, contributing to significant post-transplant morbidity. Although humoral responses are routinely monitored, the role of cellular immunity in viral control remains incompletely characterized. This study aimed to characterize BKPyV-specific T-cell responses and IgG-binding levels in healthy adults and renal transplant recipients and to explore their association with active BKPyV viruria. Methods: BKPyV DNA was screened and quantified in urine samples from eighty-two healthy adults and thirty-three renal transplant recipients, who were categorized into active, no, historical, and pre-transplant infection groups. BKPyV-specific cellular immunity was assessed in peripheral blood mononuclear cells using IFN-γ ELISPOT and T-cell proliferation assays, and IgG binding levels were measured in plasma using semi-quantitative ELISA. Results: Healthy BKPyV-positive individuals had significantly higher IFN-γ-secreting T-cell frequencies than BKPyV-negative individuals, with no significant difference in IgG levels. Transplant recipients with detectable viruria had markedly diminished IFN-γ responses compared with all other groups, whereas IgG levels remained comparable except in the pre-transplant group (n = 2). A strong negative correlation was observed between IgG levels and urine viral load in actively infected patients. Proliferation assays showed no detectable antigen-specific proliferation despite measurable cytokine secretion. Conclusions: Cellular immunity, rather than total binding IgG levels, may be more closely associated with BKPyV activity, particularly in transplant recipients. Given the exploratory cross-sectional design, prospective validation is needed. These findings support integrating cell-mediated immune assays into BKPyV monitoring to improve post-transplant risk assessment. Full article
(This article belongs to the Special Issue BK Polyomavirus: Immunopathology and Therapeutic Approaches)
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17 pages, 548 KB  
Article
Clinical Anterior Segment and Ocular Surface Findings Across Renal Replacement Modalities: Associations with CKD-Related Factors, Mineral Metabolism and Activin A
by Ioana-Madalina Bilha, Stefana Catalina Bilha, Nada Akad, Adrian Covic, Simona Hogaș, Mihai Marian Hogaș, Ioana Alina Halip, Calina Anda Sandu-Boz, Camelia Margareta Bogdanici and Irina Draga Caruntu
Life 2026, 16(8), 1294; https://doi.org/10.3390/life16081294 - 6 Aug 2026
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Abstract
Background: Chronic kidney disease (CKD) is characterized by persistent inflammation, metabolic dysregulation, and mineral and bone disorder (CKD-MBD), all of which may affect ocular tissues. While retinal manifestations of CKD have been increasingly investigated, data regarding clinical anterior segment modifications and their relationship [...] Read more.
Background: Chronic kidney disease (CKD) is characterized by persistent inflammation, metabolic dysregulation, and mineral and bone disorder (CKD-MBD), all of which may affect ocular tissues. While retinal manifestations of CKD have been increasingly investigated, data regarding clinical anterior segment modifications and their relationship with systemic biochemical parameters remain limited. Methods: We performed a cross-sectional study including 130 participants: 53 non-CKD subjects, 29 patients undergoing maintenance hemodialysis (HD), and 48 kidney transplant recipients (KTRs). All participants underwent comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement using Goldmann applanation tonometry, Schirmer I test, tear break-up time (TBUT) and assessment of cataract and blepharitis prevalence. Serum creatinine estimated glomerular filtration rate (eGFR), calcium, phosphate, parathyroid hormone (PTH), magnesium, 25-hydroxyvitamin D, and Activin A were recorded. Associations between ocular and systemic parameters were evaluated using correlation and regression analyses. Results: TBUT, Schirmer I and IOP did not differ significantly among groups (all p > 0.05). After adjustment for age, sex, BMI and diabetes mellitus (DM), HD patients showed worse visual acuity than the non-CKD reference group, reflected by higher logMAR BCVA values (adjusted B = +0.128, p = 0.024). In KTRs, higher corrected calcium was independently associated with reduced tear film parameters, correlating with both shorter TBUT (B = −0.903, p = 0.037) and lower Schirmer I values (B = −5.947, p = 0.008). Circulating Activin A increased progressively from controls to KTR to HD patients (median 189.5 vs. 273.0 vs. 314.0 pg/mL, p < 0.001) but showed no independent association with any anterior segment parameter; it was instead associated with cumulative glucocorticoid exposure (B = +1.602, p = 0.024). Conclusions: In CKD, clinical anterior segment and ocular surface differences were largely explained by age, sex, and comorbidity rather than renal replacement modality, with visual acuity deficit persisting in HD after adjusting for these covariates. At the individual level, corrected calcium was the parameter most consistently associated with tear film parameters in KTRs, whereas elevated Activin A was not independently associated with ocular involvement and likely reflects systemic disease activity. Full article
(This article belongs to the Section Medical Research)
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