Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial.
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SUBMITTER: Boissonnat P
PROVIDER: S-EPMC3533735 | biostudies-literature | 2012 Dec
REPOSITORIES: biostudies-literature
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Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial.
Boissonnat Pascale P Gaillard Ségolène S Mercier Catherine C Redonnet Michel M Lelong Bernard B Mattei Marie-Françoise MF Mouly-Bandini Annick A Pattier Sabine S Sirinelli Agnès A Epailly Eric E Varnous Shaida S Billes Marc-Alain MA Sebbag Laurent L Ecochard René R Cornu Catherine C Gueyffier François F
Trials 20121203
<h4>Background</h4>Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes.<h4>Methods</h4>In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were ce ...[more]
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Project description:BACKGROUND:Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. METHODS:In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). RESULTS:After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. CONCLUSIONS:HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen. TRIAL REGISTRATION:ClinicalTrials.gov NCT02108301.
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Project description:There is an urgent unmet need in solid organ transplantation for immunotherapeutic strategies that target B cells and plasma cells, ideally without increasing infectious complications. We conducted a phase 2 double-blind randomised placebo-controlled trial to assess the safety and potential efficacy of an anti-BLyS antibody, belimumab, in addition to standard of care immunosuppression post-kidney transplantation.
2018-06-11 | E-MTAB-5906 | biostudies-arrayexpress
Project description:Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating CD4+T-bet+ T cells, CD8+T-bet+ T cells, and CD4+FOXP3+ regulatory T cells were reduced. Single cell RNA sequencing revealed a unique expression profile in immune cells in the skin of baricitinib plus CsA treated mice, including decreased inflammatory neutrophils and increased CCR2- macrophages. In a fully major histocompatibility mismatched mismatched heart allograft model, baricitinib plus CsA prevented graft rejection for the entire 28-day treatment period compared with 9 days in controls. Our findings establish that the combination of baricitinib and CsA prevents rejection in allogeneic skin and heart graft models and supports the study of JAK inhibitors in human solid organ transplantation.
2024-06-13 | GSE269828 | GEO
Project description:AIMS:The prognostic impact of worsening renal function (WRF) in patients with acute heart failure (AHF) remains under debate. Successful decongestion might offset the negative impact of WRF, but little is known about indicators of successful decongestion in the very acute phase of AHF. We hypothesized that decongestion as evaluated by the percent reduction in brain natriuretic peptide (BNP) could identify relevant prognostic implications of WRF in the very acute phase of AHF. METHODS AND RESULTS:Data on 907 consecutive hospitalized patients with AHF in the REALITY-AHF study (age: 78±12 years; 55.1% male) were analyzed. Creatinine and BNP were measured at baseline and 48 hours from admission. WRF was defined as an increase in creatinine >0.3 mg at 48 hours from admission. The primary endpoint was 1-year all-cause mortality. Patients were divided into four groups according to the presence/absence of WRF and a BNP reduction higher/lower than the median: no-WRF/higher-BNP-reduction (n = 390), no-WRF/lower-BNP-reduction (n = 397), WRF/higher-BNP-reduction (n = 63), and WRF/lower-BNP-reduction groups (n = 57). Kaplan-Meier curve analysis showed that the WRF/lower-BNP-reduction group had a worse prognosis than the other groups. In a Cox regression analysis, only the WRF/lower-BNP-reduction group had higher mortality compared to the no-WRF/higher-BNP-reduction group (hazard ratio: 3.34, p<0.001). CONCLUSION:In the very acute phase of AHF, BNP reduction may aid in identifying relevant prognostic significance of WRF.
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