Kidney transplantation is a crucial treatment for end-stage kidney disease, with immunosuppressive drugs helping to reduce acute rejection rates. However, kidney graft longevity remains a concern. This study explores the role of indoleamine 2,3-dioxygenase 1 (IDO1) in kidney transplant immunology. IDO1 breaks down tryptophan, affecting immune cell behavior, primarily T-cells. The research focuses on both cellular and antibody-mediated immune responses, often causing graft damage. The study assessed IDO1 expression in renal transplant biopsies from patients with graft function decline, examining its connection to clinical parameters. A total of 121 biopsy samples were evaluated for IDO1 expression using immunohistochemistry. Patients were categorized as IDO1(+) positive or IDO1(−) negative based on immunoreactivity in tubular epithelium. Results showed a significant link between IDO1 expression and rejection incidence. IDO1(+) positive patients had lower rejection rates (32.9%) compared to IDO1(−) negative ones (62.2%) [p = 0.0017], with substantial differences in antibody-mediated rejection (AMR) (5.2% vs. 20%) [p = 0.0085] and T-cell mediated rejection (TCMR) (31.6% vs. 57.8%). These associations suggest that IDO1 may play a protective role in kidney transplant rejection. IDO1 modulation could offer novel therapeutic avenues to enhance graft survival. The study underscores IDO1 as a potential marker for rejection risk assessment, with its potential applications in personalized interventions and improved patient outcomes. Further research is needed to fully comprehend the mechanisms behind IDO1’s immunomodulatory functions and its potential clinical translation.
This case report describes a 59-year-old male patient after heart and kidney transplantation, subsequently diagnosed with refractory hypertension since implemented antihypertensive pharmacotherapy consisting of six agents did not provide a substantial therapeutic response. Elevated blood pressure and its impact on a hypertrophied transplanted heart and impaired renal graft function have led to a significant deterioration in the patient’s cardiovascular risk profile. To address this issue, a native renal arteries denervation was performed. It resulted in a noteworthy decrease in both systolic and diastolic pressure values, thus manifesting a positive hypotensive effect. Furthermore, a sustainable reduction of left ventricular mass and stabilization in kidney graft function were noticed. The presented case provides evidence that renal denervation can be an efficacious complementary treatment method in individuals who received kidney and heart grafts as it leads to a decrease in cardiovascular risk.
6 February 2023 in Annales Academiae Medicae Silesiensis
Wstęp: Styl życia jest głównym determinantem zdrowia, może jednak zmieniać się z biegiem lat. Studentów cechują zwykle „gorsze” zachowania zdrowotne niż te u osób dorosłych. To ciekawe zjawisko nie było badane w środowisku lekarskim. Celem pracy była ocena stylu życia lekarzy w porównaniu z ich zachowaniami z lat studenckich.Materiał i metody: Badanie przekrojowe przeprowadzono w 2020 r. z wykorzystaniem autorskiego kwestionariusza oceniającego różne elementy stylu życia, które klasyfikowano jako „zdrowe” lub „niezdrowe” na podstawie rekomendacji Światowej Organizacji Zdrowia. W badaniu uczestniczyło 112 lekarzy (64,3% mężczyzn i 35,7% kobiet); mediana wieku wynosiła 37 lat (IQR 36–38). Wyniki porównano z danymi otrzymanymi w tej grupie na podstawie tego samego kwestionariusza dystrybuowanego w latach 2003–2005, tj. gdy badani byli studentami medycyny.Wyniki: Zaobserwowano istotne, korzystne zmiany dotyczące rzadszego spożycia posiłków z dużą zawartością soli kuchennej (p < 0,01) oraz częstszego spożycia warzyw i owoców (p < 0,01). Zaobserwowano zwiększenie częstości picia kawy (p < 0,01). W pozostałym zakresie nawyki żywieniowe i stosowanie używek pozostawały niezmienne. Nie stwierdzono różnic dotyczących aktywności fizycznej, występowania stresu oraz jego charakteru (mobilizujący/destabilizujący).Wnioski: Styl życia lekarzy nie zmienia się znacząco w porównaniu z latami studenckimi, co można wiązać z przyzwyczajeniami z lat młodości.
Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker of kidney allograft injury. Elevated dd-cfDNA has been associated with acute rejection, particularly antibody-mediated rejection; however, dd-cfDNA reflects graft-derived tissue injury rather than a specific alloimmune mechanism. Its interpretation may therefore be challenging in conditions characterized by endothelial and microvascular injury, such as atypical hemolytic uremic syndrome (aHUS). This retrospective observational study included 14 kidney transplant recipients who underwent their first kidney transplantation at Wroclaw Medical University between April and December 2022. Twelve non-aHUS recipients with stable renal function and two recipients with aHUS were assessed. Plasma samples were collected at four early post-transplant time points: day 7 (D7), day 14 (D14), month 1 (M1), and month 2 (M2). dd-cfDNA was measured using next-generation sequencing with the AlloSeq cfDNA assay. Donor-specific anti-HLA antibodies (DSA) were assessed using single-antigen bead testing. In non-aHUS recipients, median %dd-cfDNA declined from 0.72% [0.28%, 2.33%] at D7 to 0.12% [0.05%, 0.34%] by M1. In contrast, recipients with aHUS demonstrated persistently elevated dd-cfDNA values fluctuating around 1% [0.88%, 1.14%] during the first month of follow-up. No DSA were detected in any patient during the observation period. No apparent correlation was observed between %dd-cfDNA and serum creatinine in this small cohort. In this preliminary observational study, kidney transplant recipients with aHUS showed persistently elevated early post-transplant dd-cfDNA despite the absence of detectable DSA, absence of clinically documented rejection, and preserved graft function during follow-up. These findings suggest that universal dd-cfDNA thresholds may require cautious interpretation in aHUS. Larger biopsy-anchored studies integrating complement and endothelial injury markers are needed to clarify whether dd-cfDNA elevation in aHUS reflects alloimmune injury, complement-mediated microvascular injury, or overlapping mechanisms.
Monitoring immunosuppression in kidney transplant recipients remains challenging, as conventional therapeutic drug monitoring (TDM) reflects pharmacokinetic exposure rather than the overall functional immune state. Torque teno virus (TTV), a non-pathogenic virus, has emerged as a potential complementary biomarker of the net state of immunosuppression. This review evaluates the current evidence regarding the utility of TTV load in this context, focusing on its correlation with standard pharmacokinetic markers, the analytical performance of quantitative PCR assays, its role as an integrated marker of immunosuppression, and its predictive value for clinical outcomes. Available data indicate that TTV load shows weak and inconsistent correlations with individual drug levels, such as tacrolimus trough concentrations, supporting its role as a complementary rather than substitutive tool. qPCR-based assays demonstrate generally good sensitivity and reproducibility, although inter-assay variability and lack of standardization remain important limitations. Clinically, higher TTV levels have been associated with an increased risk of opportunistic infections, whereas lower levels have been linked to acute rejection, suggesting a potential association between TTV viremia and immune status. TTV monitoring may represent a promising complementary approach for a more individualized assessment of immunosuppression. However, further prospective and interventional studies are required to validate standardized thresholds and determine whether TTV-guided strategies improve transplant outcomes compared with conventional monitoring.
Background/Objectives: COVID-19 may result in persistent symptoms, some of which can be disabling, referred to as post-acute sequelae of SARS-CoV-2 (PASC, or long COVID). The growing recognition of PASC as a public health challenge underscores the need for comprehensive studies of its course, risk factors, and clinical outcomes. This multicentric study aimed to compare the prevalence, symptom spectrum, and functional impact of PASC in two patient groups: those hospitalized with COVID-19 and those managed exclusively in ambulatory care. Methods: Molecular, clinical, and demographic data were obtained from 319 patients diagnosed with COVID-19 in seven European countries. Patients were classified as PASC in accordance with the WHO definition. Results: PASC is more frequent and severe among hospitalized patients, while ambulatory patients present with milder but prolonged symptoms. Categorical age analysis suggests that older age was associated with a higher incidence of PASC, highlighting the need for multidisciplinary management and targeted support. Conclusions: Our findings highlight distinct differences in the presentation and impact of PASC across patient groups, with important implications for individualized care, multidisciplinary management, and effective healthcare planning in the post-pandemic era.