Increased Incidence of Acute Graft Rejection on Calcineurin Inhibitor–Free Immunosuppression After Heart Transplantation

Celik, Sultan; Doesch, Andreas O.; Konstandin, Mathias; Kristen, Arnt V.; Ammon, K.; Sack, Falk–Udo; Katus, Hugo A.; Dengler, Thomas J.

doi:10.1016/j.transproceed.2010.12.059

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…This is in accordance with the study by Celik et al. . However, a more refined analysis showed a highly significant association with a history of late rejection, that is, those episodes occurring after the initial (one yr) period after transplantation.…”

Section: Discussionsupporting

confidence: 92%

“…This is in accordance with the safety profile observed in previous studies , in which all the patients were treated with mycophenolate mofetil. However, concomitant steroid therapy showed only a non‐significant trend to lower incidence of rejection after conversion, again in coincidence with previous reports .…”

Section: Discussionsupporting

confidence: 90%

“…. Although this agrees well with the time course of rejection after transplantation, it could also be biased by the higher biopsy rates in the first year after transplantation .…”

Section: Discussionsupporting

confidence: 82%

“…In observational studies , the rejection rate averaged 5.8% (range: 0–26.6%). In a recent retrospective study, the incidence of rejection episodes per patient‐month was significantly higher on CNI‐free patients as compared with conventional CNI patients .…”

mentioning

confidence: 95%

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Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

González‐Vílchez

Prada

Paniagua

et al. 2013

Clinical Transplantation

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We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

“…. Although this agrees well with the time course of rejection after transplantation, it could also be biased by the higher biopsy rates in the first year after transplantation .…”

Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 95%

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Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

González‐Vílchez

Prada

Paniagua

et al. 2013

Clinical Transplantation

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“…Mitogen-activated protein kinase (MAPK) is a key molecular signaling pathway in eukaryotes and serves an essential function in regulating cellular structure and functional activities (6). In eukaryotes, the MAPK signaling channel contains several subfamilies including p38, extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and ERK5 (6). A previous study demonstrated that the p38, ERK and JNK signal transduction pathways had a marked association with cartilage injury identified in RA (7).…”

Section: Introductionmentioning

confidence: 99%

Combined treatment with sinomenine and acupuncture on collagen‑induced arthritis through the NF‑κB and MAPK signaling pathway

Liu

Wan

et al. 2018

Oncol Lett

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Sinomenine is a monomer extracted from the traditional Chinese medicine plant , which possesses several pharmacological properties including prominent abirritation, mitigation, anti-inflammation, immune suppression, cough relief, stimulation of histamine release, decrease in blood pressure and antiarrhythmia. Sinomenine is clinically employed to treat rheumatic disease. To investigate the impact of combined sinomenine treatment with acupuncture on the progression of arthritis and explore the potential underlying molecular mechanisms, the present study analyzed a collagen-induced arthritis model. Results from the combined curative (CC) treatment group (combined treatment with sinomenine and acupuncture) demonstrated a decrease in volume changes and arthritis score changes within rat paws, and increased the overall body weight in arthritic rats. CC treatment significantly decreased tumor necrosis factor α, interleukin (IL)-6, IL-1β and IL-8 serum levels in arthritic rats. CC treatment significantly increased superoxide dismutase and inhibited malondialdehyde levels in arthritic rats. The protein expression of cyclooxygenase-2, inducible nitric oxide synthase, matrix metalloproteinase (MMP)2 and MMP9 in arthritic rats was suppressed owing to CC treatment. Finally, nuclear factor κB and phosphorylated p38 mitogen-activated protein kinase (MAPK) protein expression in arthritic rats were also suppressed following CC treatment. The results indicate that the combined treatment of sinomenine and acupuncture on collagen-induced arthritis takes effect through the nuclear factor κB and MAPK signaling pathway.

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Chronic Renal Insufficiency in Heart Transplant Recipients: Risk Factors and Management Options

González‐Vílchez

Prada

2014

Drugs

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Renal dysfunction after heart transplantation is a frequently observed complication, in some cases resulting in significant limitation of quality of life and reduced survival. Since the pathophysiology of renal failure (RF) is multifactorial, the current etiologic paradigm for chronic kidney disease after heart transplantation relies on the concept of calcineurin inhibitor (CNI)-related nephrotoxicity acting on a predisposed recipient. Until recently, the management of RF has been restricted to the minimization of CNI dosage and general avoidance of classic nephrotoxic risk factors, with somewhat limited success. The recent introduction of proliferation signal inhibitors (PSIs) (sirolimus and everolimus), a new class of immunosuppressive drugs lacking intrinsic nephrotoxicity, has provided a completely new alternative in this clinical setting. As clinical experience with these new drugs increases, new renal-sparing strategies are becoming available. PSIs can be used in combination with reduced doses of CNIs and even in complete CNI-free protocols. Different strategies have been devised, including de novo use to avoid acute renal toxicity in high-risk patients immediately after transplantation, or more delayed introduction in those patients developing chronic RF after prolonged CNI exposure. In this review, the main information on the clinical relevance and pathophysiology of RF after heart transplantation, as well as the currently available experience with renal-sparing immunosuppressive regimens, particularly focused on the use of PSIs, is reviewed and summarized, including the key practical points for their appropriate clinical usage.

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Increased Incidence of Acute Graft Rejection on Calcineurin Inhibitor–Free Immunosuppression After Heart Transplantation

Cited by 7 publications

References 22 publications

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

Combined treatment with sinomenine and acupuncture on collagen‑induced arthritis through the NF‑κB and MAPK signaling pathway

Chronic Renal Insufficiency in Heart Transplant Recipients: Risk Factors and Management Options

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