Son dönem böbrek yetmezliğinde aterojenisite ve asimetrik dimetilarjininin yeri
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Dosyalar
Tarih
2012
Yazarlar
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Asimetrik dimetilarginin, esas olarak endojen nitrik oksit sentaz inhibitörüdür. Endojen anti-aterosklerotik molekül` olarak bilinen nitrik oksit, major endotel kaynaklı vazoaktif mediatörüdür. Dolayısıyla asimetrik dimetilarginin endotel disfonksiyonu ile ilgili anahtar rolü oynayabileceği düşünülmektedir. Nitrik oksit sentazın endojen yarışmalı bir inhibitörü olan asimetrik dimetilarginin, kardiyovasküler ve böbrek hastalıklarının bir biyobelirteci olarak tanımlanmaktadır. Son dönem böbrek yetmezliği olan hastalarda asimetrik dimetilarginin, endotelyal disfonksiyon ve kardiyovasküler hastalıkların bağımsız bir belirleyicisi olarak ortaya çıkmıştır. Bu çalısmanın amacı, son dönem böbrek yetmezligi olan hastalarda asimetrik dimetilarginin düzeyleri ile ateroskleroz gelişimi arasındaki ilişkinin kardiyovasküler hastalıklar açısından değerlendirilmesidir. Çalışmamızda, 31 hemodiyaliz tedavisi, 28 periton diyalizi tedavisi ve 25 prediyaliz hastada asimetrik dimetilarjininin ateroskleroz geli?imindeki yeri ara?tırıldı. Henüz renal replasman tedavisi almayan prediyaliz grubu hastalarına kıyasla hemodiyaliz tedavisi gören hastalarımızda, ateroskleroz göstergesi olan karotis arter intima-media kalınlığı anlamlı artmış (p=0.016) bulundu. Periton diyalizi uygulanan hastaların asimetrik dimetilarjinin düzeylerinin, hemodiyaliz uygulanan hastalara göre 0,1 ?mol/L düşük olduğu saptandı. Hastalarımızda, asimetrik dimetilarjinin ile karotis arter ortalama intima-media kalınlığı (r=0.371; p=0.001) ve interlökin-6 düzeyi (r=0.240; p=0.035) pozitif doğrusal ili?kili bulundu. ?ntima media kalınlığı ile erkek cinsiyet (r=0.397; p<0.001), IL-6 (r=0.321; p=0.004), sigara içimi (r=0.283; p=0.009), diyaliz tedavisi alma (r=0.270; p=0.013), serum kreatinin (r=0.377; p=0.015) pozitif; yüksek molekül ağırlıklı lipoprotein (-r=0.236; p=0.031) negatif doğrusal ilişkili saptandı. Interlökin-6 değeri karotis arter ortalama intima-media 60 kalınlığı (r=0.403; p<0.001), fibrinojen (r=0.322; p=0.004) ve intersellüler adezyon molekülü-1 (r=0.261; p=0.021) ile pozitif doğrusal ili?kili bulundu. Özetle, hastalarımızdaki atreoskleroz geli?iminde geleneksel ateroskleroz risk faktörlerinin yanı sıra artmış asimetrik dimetilarginin düzeyi ve inflamasyon artışı gibi yeni risk faktörlerinin etkili olduğunu saptadık. Periton diyalizi tedavisinin asimetrik dimetilarginin temizleme gücünün hemodiyaliz tedavisine göre daha yüksek olabileceğini gözlemledik. Bulgularımız, asimetrik dimetilarjinin ve interlökin-6 düzeylerini azaltmaya yönelik tedavi yöntemlerinin erken dönemde uygulanabilmesi durumunda, kronik böbrek hastalarında gözlenen erken-hızlanmış ateroskleroz gelişimi ve buna bağlı kardiyovasküler morbidite ve mortalitenin azaltılabileceğini dü?şündürmüştür.
Abstract
Asymmetric dimethylarginine is the principal endogenous inhibitor of nitric oxide synthase. One of the major endothelium-derived vasoactive mediators is nitric oxide, which has been characterized as an endogenous -anti-atherosclerotic molecule. Thus, asymmetric dimethylarginine might be thought as a key role contributing to endothelial dysfunction. Asymmetric dimethylarginine, an endogenous competitive inhibitor of nitric oxide synthase, is increasingly recognized as a putative biomarker in cardiovascular an renal diseases. Asymmetric dimethylarginine has emerged as an independent predictor of endothelial dysfunction and cardiovascular disease in patients with end-stage renal disease. The goal of this study was to examine the relationship between asymmetric dimethylarginine and atherosclerosis development for cardiovascular diseases in patients with end-stage renal failure. Our study aimed to define the role of asymmetric dimethylarginine in atherosclerosis development in 31 patients with hemodialysis treatment, 28 patients with peritoneal dialysis treatment and 25 patients with end-stage renal failure who did not take any renal replacement therapy yet. Intima and media thickness of carotid artery were found to be significantly (p=0.016) increased in patients with hemodialysis treatment compared to predialysis group who did not take any renal replacement therapy, indicating existence of atherosclerosis. Asymmetric dimethylarginine levels were 0,1 ?mol/L decreased in patients with treatment peritonea dialysis compared to hemodialysis. Patient average intima and media thickness of carotid artery (r=0.371; p=0.001) and interleukin-6 levels (r=0.240; p=0.035) were positively correlated with asymmetric dimethylarginine levels. Patient male sex (r=0.397; p<0.001), asymmetric dimethylarginine (r=0.371; p=0.001), interleukin-6 (r=0.321; p=0.004), cigarette (r=0.283; p=0.009), renal replacement therapy (r=0.270; p=0.013), serum creatinine (r=0.377; p=0.015) were positively and high density lipoprotein (-r=0.236; p=0.031) was negatively correlated with intima and media thickness of carotid artery. Patient average intima and media thickness of carotid artery (r=0.403; p<0.001), fibrinogen (r=0.322; p=0.004), intercellular adhesion molecule-1 (r=0.261; p=0.021) were positively correlated with interleukin-6 levels. In conclusion, we found that increased levels of asymmetric dimethylarginine, and new risk factors such as increased inflammation were effective as well as traditional atherosclerosis risk factors in the development of atherosclerotic disease. We observed that cleaning power of asymmetric dimethylarginine may be higher in the treatment peritoneal dialysis than the hemodialysis therapy. Our results suggest that therapies aiming to reduce the levels of asymmetric dimethylarginine and interleukin-6 in early period would prevent the development of early and accelerated atherosclerosis in chronic renal diseases, hence increased cardiovascular rmorbidity and mortality.
Abstract
Asymmetric dimethylarginine is the principal endogenous inhibitor of nitric oxide synthase. One of the major endothelium-derived vasoactive mediators is nitric oxide, which has been characterized as an endogenous -anti-atherosclerotic molecule. Thus, asymmetric dimethylarginine might be thought as a key role contributing to endothelial dysfunction. Asymmetric dimethylarginine, an endogenous competitive inhibitor of nitric oxide synthase, is increasingly recognized as a putative biomarker in cardiovascular an renal diseases. Asymmetric dimethylarginine has emerged as an independent predictor of endothelial dysfunction and cardiovascular disease in patients with end-stage renal disease. The goal of this study was to examine the relationship between asymmetric dimethylarginine and atherosclerosis development for cardiovascular diseases in patients with end-stage renal failure. Our study aimed to define the role of asymmetric dimethylarginine in atherosclerosis development in 31 patients with hemodialysis treatment, 28 patients with peritoneal dialysis treatment and 25 patients with end-stage renal failure who did not take any renal replacement therapy yet. Intima and media thickness of carotid artery were found to be significantly (p=0.016) increased in patients with hemodialysis treatment compared to predialysis group who did not take any renal replacement therapy, indicating existence of atherosclerosis. Asymmetric dimethylarginine levels were 0,1 ?mol/L decreased in patients with treatment peritonea dialysis compared to hemodialysis. Patient average intima and media thickness of carotid artery (r=0.371; p=0.001) and interleukin-6 levels (r=0.240; p=0.035) were positively correlated with asymmetric dimethylarginine levels. Patient male sex (r=0.397; p<0.001), asymmetric dimethylarginine (r=0.371; p=0.001), interleukin-6 (r=0.321; p=0.004), cigarette (r=0.283; p=0.009), renal replacement therapy (r=0.270; p=0.013), serum creatinine (r=0.377; p=0.015) were positively and high density lipoprotein (-r=0.236; p=0.031) was negatively correlated with intima and media thickness of carotid artery. Patient average intima and media thickness of carotid artery (r=0.403; p<0.001), fibrinogen (r=0.322; p=0.004), intercellular adhesion molecule-1 (r=0.261; p=0.021) were positively correlated with interleukin-6 levels. In conclusion, we found that increased levels of asymmetric dimethylarginine, and new risk factors such as increased inflammation were effective as well as traditional atherosclerosis risk factors in the development of atherosclerotic disease. We observed that cleaning power of asymmetric dimethylarginine may be higher in the treatment peritoneal dialysis than the hemodialysis therapy. Our results suggest that therapies aiming to reduce the levels of asymmetric dimethylarginine and interleukin-6 in early period would prevent the development of early and accelerated atherosclerosis in chronic renal diseases, hence increased cardiovascular rmorbidity and mortality.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Son Dönem Böbrek Hastalığı, Asimetrik Dimetilarjinin, Nitrik Oksit, Ateroskleroz, End-stage Renal Disease, Asymmetric Dimethylarginine, Nitric Oxide, Atherosclerosis
