25 research outputs found
IN-VITRO STUDY OF NGAL IMMUNOMODULATORY EFFECT IN HEMODIALYSIS AND HYPERIMMUNIZED PATIENTS
No full textBackground: In recent years, an increasing number of patients waiting for kidney transplant, showed the presence of alloantibodies against HLA antigens, and non-HLA. Evidence demonstrates the contribution of regulatory T cells (Treg) in modulating the immune response in different animal models and in clinical transplant, to suggest their potential use as markers of tolerance, rejection or prediction of organ transplant outcome. We have previously provided in vitro evidence that NGAL (neutrophil gelatinase associated lipocalin), a known biomarker of renal injury, is able to induce immune tolerance by upregulating HLA-G expression and expansion of T regulatory cells in normal subjects. In this study, we evaluated the effect of NGAL on expression of HLA-G and influence on Treg populations in hemodialysis and hyperimmune patients.
Methods: We enrolled 30 subjects divided in 3 groups: 10 healthy subjects, 10 uremic patients on hemodialysis and 10 hyperimmunized patients. We carried out isolation and characterization of immunophenotypic lymphocyte population Treg from peripheral blood mononuclear cells (PBMCs).
Results: Following treatment with increased doses of NGAL (80–640 ng/ml), an increased expression of HLA-G was observed in the population of CD4+ CD25+ FOXP3+ in patients on hemodialysis. This increase is also proportional to the percentage of Treg themselves in PBMCs and comparable to healthy controls
Impact of the Type of Dialysis on Time to Transplantation: Is It Just a Matter of Immunity?
No full textBackground: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies
An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells
No full textBackground: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress. Materials and methods: Lactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide. Results: HB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9. Conclusion: This in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling
Longitudinal Analysis of Cardiovascular Risk Factors in Active and Sedentary Kidney Transplant Recipients
No full textDespite the benefits of physical activity on cardiovascular risk in kidney
transplant recipients (KTRs), the long-term effects of exercise have been poorly investigated. This is a
three-year observational study comparing graft function and cardiovascular risk factors in active
KTRs (AKTRs) vs. sedentary KTRs (SKTRs). Methods: KTRs with stable renal function were assigned
to active or sedentary group in relation to the level of daily physical activity based on World Health
Organization (WHO) recommendations (<150 or >150 min/week, respectively). Complete blood
count, renal function indices, lipid profile, blood pressure and anthropometric measures were collected
yearly for an observation period of three years. The comparisons between the two groups were
performed by repeated measures analyses of covariance (ANCOVAs), with age as a covariate. Results:
Fifty-four subjects were included in the study. Thirty of them were identified as AKTRs (M/F 26/4,
aged 45 ± 12 years) and 24 as SKTRs (M/F 18/6, aged 51 ± 14 years). Baseline characteristics were
similar between the groups except body mass index (BMI) that was significantly higher in SKTRs
(p = 0.043). Furthermore, over the three-year observation period, BMI decreased in AKTRs and
increased in SKTRs (p = 0.006). Graft function was stable in AKTRs, while it showed a decline
over time in SKTRs, as indicated by the rise in serum creatinine levels (p = 0.006) and lower eGFR
(p = 0.050). Proteinuria, glucose and uric acid levels displayed a decrease in AKTRs and an increase
in SKTRs during the three-year period (p = 0.015, p = 0.004 and p = 0.013, respectively). Finally,
concerning lipid profiles, AKTRs had a significant reduction over time of triglycerides levels, which
conversely showed a clinically relevant increase in SKTRs (p = 0.014). Conclusions: Our findings
indicate that regular weekly exercise training may counteract the increased cardiovascular risks and
also prevent graft function decline in KTRs
Impact of Single Hemodialysis Treatment on immune Cell Subpopulations
No full textHemodialysis (HD) is known to trigger a chronic inflammatory status, affecting the innate and acquired immune response. This study was aimed at a comparative analysis of immune cell subsets, proliferation, and apoptosis in subjects receiving chronic HD treatment with respect to a healthy control. Regardless of the dialysis filter used, we observed a reshaping of the acquired immune component both with respect to healthy patients and between the various sessions of dialysis treatment, with an impairment of CD3 cells, along with an increase in CD4 and CD8 cell populations producing pro-inflammatory factors such as IL-17 and IFN-gamma. The population of B cells, monocytes and NK cells were not impaired by the dialysis procedure. These results confirmed the high impact of the HD treatment on the patient’s immune system, underlying the imbalance of T cell counterparts
Role of killer-cell immunoglobulin-like receptor and human leucocyte antigen in kidney transplantation
No full text
Eparina non frazionata vs eparina a basso peso molecolare: effetti sui livelli plasmatici di osteoprotegerina, RANKL e citochine infiammatorie in dialisi
No full text
An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells
No full textOlga Baraldi,1 Francesca Bianchi,2,3 Viola Menghi,1 Andrea Angeletti,1 Anna Laura Croci Chiocchini,1 Maria Cappuccilli,1 Valeria Aiello,1 Giorgia Comai,1 Gaetano La Manna1 1Department of Experimental, Diagnostic and Specialty Medicine, Nephrology, Dialysis and Renal Transplant Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, 2Stem Wave Institute for Tissue Healing, Gruppo Villa Maria Care & Research – Ettore Sansavini Health Science Foundation, Lugo, Ravenna, 3National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Background: Acute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress.Materials and methods: Lactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide.Results: HB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9.Conclusion: This in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling. Keywords: acute kidney injury, apoptosis, hyaluronan ester of butyric acid, mesangial cell
