Başkent Üniversitesi Makaleler

Permanent URI for this collectionhttps://hdl.handle.net/11727/13096

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Subject: search.filters.subject.Immunosuppressive drugs

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    Determinants of Fasting Total Serum Homocysteine Levels in Liver Transplant Recipients
    (Başkent Üniversitesi, 2006-06) Akoglu, Bora; Wondra, Kathrin; Caspary, Wolfgang F.; Dominik, Faust
    Objectives: Homocysteine (HCY) is a sulfur-containing amino acid considered to be a marker for a relative folate deficiency. Hyperhomocysteinemia is a known risk factor for development of cardiovascular disease, vascular dementia, depression, and possibly some carcinogeneses. Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. The aim of this study is to elucidate the determinants for hyperhomocysteinemia as an additional risk factor in these patients. Materials and Methods: Seventy stable liver transplant recipients, 48 men (mean age, 50 ± 11 years) and 22 women (mean age, 52 ± 13 years) had their serum homocysteine levels tested after orthotopic liver transplantation. For mainstay immunosuppression, 53 patients were treated with tacrolimus, 10 with cyclosporine, 3 with mycophenolate mofetil, and 4 with sirolimus. Fasting blood samples were obtained and analyzed immediately (within 1 hour) for total serum homocysteine by high-performance liquid chromatography. Results: In all patients, mean homocysteine levels were 22.7 ± 14 µmol/L (normal range, 9-15 µmol/L). Forty-six patients were found to have homocysteine levels > 15 µmol/L, and all 70 recipients had homocysteine levels > 9 µmol/mL. In our patients, increased homocysteine levels correlated well with body mass index and renal function. Homocysteine levels in patients receiving cyclosporine were higher than those in patients receiving tacrolimus (22.3 ± 6 vs 17.9 ± 12 µmol/L, P < .05). Conclusions: Overall, homocysteine levels are significantly increased in liver transplant recipients. Homocysteine levels correlate well with obesity, renal function, and the particular immunosuppressant protocol. Therefore, a specific treatment for patients after liver transplantation (eg, one with folates) might reduce the risk of complications resulting from hyperhomocysteinemia.
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    Ageing and Immunosuppression in Kidney Transplantation
    (Başkent Üniversitesi, 2004-12) Land, Walter Gottlieb
    Modern approaches to tailor-made, individualized immunosuppressive therapy for patients receiving organ transplantation require a rethinking of therapeutic strategies when it comes to older persons receiving kidney transplants, especially from deceased older donors. This review article makes the case for the use of calcineurin-inhibitor–free immunosuppressive induction/maintenance protocols in this “worst-case scenario” and discusses the theoretical and clinical data that support this recommendation. We will discuss modern theories of ageing, emphasizing the free-radical theory in relation to new insights into the mechanisms of innate immunity. In this context, a new, modified theory of ageing is presented. Increased generation of reactive oxygen species during ageing, via increased leakage of these oxidizing molecules from mitochondria, may contribute to senescence and age-related diseases by direct damage to intracellular DNA, proteins, and lipids. In addition, free-radical–mediated tissue injury, accompanied by induction of damage-associated molecular patterns, may result in activation of both inflammatory and vascular cells of the innate immune system, contributing (via inflammatory processes) to ageing and age-related diseases such as atherosclerosis. Calcineurin-inhibiting agents have been shown to induce oxidative stress and are thus defined as “proageing” drugs. Their use in older patients may aggravate the preexisting oxidized intracellular state and therefore should be avoided. In contrast, inosine-monophosphate dehydrogenase–inhibiting agents such as mycophenolate mofetil have been shown to even ameliorate oxidative stress and are thus defined as “antiageing” drugs. Therefore, their use for immunosuppression in older patients receiving kidney transplantation is suggested. This recommendation is supported by data from a prospective trial on the application of a calcineurin-inhibitor–free, mycophenolate-mofetil–based indu-ction/maintenance immunosuppressive protocol in older recipients of kidneys from deceased older donors: the 5-year patient and 5-year allograft survival rates are currently 87% and 70%, respectively.