Kronik böbrek hastalığında aterojenisite; etkileyen faktörler ve asimetrik dimetilarjininin yeri
Atherogenicity in chronic renal disease: affecting factors and the role of asymetric dimethylarginine
Yazar: SEVAL AKPINAR
Danışman: YRD. DOÇ. SEDAT ÜSTÜNDAĞ
Trakya Üniversitesi / Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2009
Konu: Nefroloji = Nephrology
Dizin: Ateroskleroz = Atherosclerosis ; Böbrek yetmezliği-kronik = Kidney failure-chronic

Özet:
Asimetrik dimetilarjininin kronik böbrek hastalığı (KBH) ndaki erken-hızlanmış ateroskleroz gelişiminde önemli rolü olabileceği düşünülmektedir. Çalışmamızda 32 sağlıklı birey ve 3-4 KBH olan 65 hastada asimetrik dimetilarjininin ateroskleroz gelişimindeki yeri araştırıldı.Sağlıklı kontrol grubuna göre hastalarımızda, ateroskleroz göstergesi olan karotis arter intima-media kalınlığı belirgin artmış (p=0.0004) bulundu. Hastalarımızda, intima media kalınlığı ile hasta yaşı (r=0.619; p<0.001), malondialdehit (r=0.434; p=0.005), C-reaktif protein (r=0.482; p<0.003), sistolik kan basıncı (r=0.402; p=0.009), bel/kalça oranı (r=0.377; p=0.015), diyastolik kan basıncı (r=0.332; p=0.034), asimetik dimetilarjinin (r=0.320; p<0.041), homosistein (r=0.335; p=0.043), ve üriner protein atılımı (r=0.308; p=0.049) pozitif; total nitrit/serum kreatinin oranı (-r=0.415; p=0.011) negatif doğrusal ilişkili bulundu. Çok değişkenli nedensellik ilişkisi araştırmasında sadece hasta yaşı (p=0.00007) ve plazma asimetrik dimetilarjinin düzeyinin (p=0.03) intima media kalınlığının bağımsız belirleyicileri olduğu; yaşdaki her 1 yıl artışın intima media kalınlığını 0.011 mm, asimetrik dimetilarjinin düzeyindeki her 1 ?mol/L artışın intima media kalınlığını 0.336 mm artırdığı saptandı.Hastalarımızda, asimetrik dimetilarjinin düzeyleri E-selektin (r=0.376; p=0.004), C-reaktif protein (r=0.335; p=0.012), homosistein (r=0.305; p=0.022) ve malondialdehit (r=0.282; p=0.025) ile pozitif; Arjinin/ asimetrik dimetilarjinin (-r=0.573; p=0.001) ve total nitrit/serum kreatinin oranı (-r=0.362; p=0.006) negatif doğrusal ilişkili bulundu. Çok değişkenli nedensellik ilişkisi araştırmasında sadece C-reaktif proteinin (p=0.002) plazma asimetrik dimetilarjinin düzeyinin bağımsız belirleyicisi olduğu, her 1 mg/dL C-reaktif proteinin artışının plazma ADMA düzeyini 0.100 µmol/L artırdığı saptandı.Özetle, çalışmamızda hasta yaşı ve plazma asimetrik dimetilarjinin artışının ateroskleroz gelişiminin bağımsız belirleyicileri olduğunu saptadık. Hastalarımızdaki asimetrik dimetilarjinin artışından, öncelikle inflamasyon artışı ile ilişkili gelişen yıkılım azlığının sorumlu olabileceğini belirledik. Bulgularımız, hastalarımızda aterosklerozun bağımsız ve değiştirilebilir tek bağımsız göstergesi olarak ortaya çıkan plazma asimetrik dimetilarjinin düzeylerini azaltmaya yönelik tedavi yöntemlerinin geliştirilerek-uygulanabilmesi durumunda, kronik böbrek hastalarında gözlenen erken-hızlanmış ateroskleroz gelişiminin azaltılabileceğini düşündürmüştür.

Abstract:
Asymmetric dimethylarginine may play an important role in early-accelerated atherosclerosis development in patients with chronic renal disease. Our study aimed to define the role of asymmetric dimethylarginine in atherosclerosis development in 32 healthy controls and 65 patients with chronic renal disease.Intima and media thickness of carotid artery were found to be significantly (p=0.0004) increased in patients compared to controls, indicating existence of atherosclerosis. Patient age (r=0.619; p<0.001), malondialdehyde (r=0.434; p=0.005), C-reactive protein (r=0.482; p<0.003), systolic blood pressure (r=0.402; p=0.009), waist/hip ratio (r=0.377; p=0.015), diastolic blood pressure (r=0.332; p=0.034), ADMA (r=0.320; p<0.041), homocysteine (r=0.335; p=0.043), urinary protein excretion (r=0.308; p=0.049) were positively and total nitrite/serum creatinine ratio was (-r=0.415; p=0.011) negatively correlated with intima and media thickness of carotid artery. In multivariate analysis only patient age (p=0.00007) and plasma asymmetric dimethylarginine level (p=0.03) were found to be independent predictors of intima and media thickness of carotid artery. Increase of each one year in patient age and 1 ?mol/L plasma asymmetric dimethylarginine level resulted an increase of 0.011 (0.06-0.16) mm and 0.336 (0.035-0.637) mm in intima and media thickness of carotid artery independent of other factors, respectively.In our patients e-selectin (r=0.376; p=0.004), C-reactive protein (r=0.335; p=0.012), homocysteine (r=0.305; p=0.022) ve MDA (r=0.282; p=0.025) were positively and arginine/ asymmetric dimethylarginine (-r=0.573; p=0.001) ratio and total nitrit/serum creatinine ratio (-r=0.362; p=0.006) were negatively correlated with asymmetric dimethylarginine levels. But multivariate analysis revealed that only C-reactive protein (p=0.002) was found to be an independent predictor of increased asymmetric dimethylarginine level and each increase of 1 mg/dL in C-reactive protein level resulted in 0.1 mm increase of intima and media thickness of carotid artery.In conclusion, we showed that patient age and plasma asymmetric dimethylarginine level were independent predictors of atherosclerosis development. We also revealed that decreased metabolism as a result of inflammation could be responsible for increased plasma asymmetric dimethylarginine levels in our patients. Our results suggest that therapies aiming to decrease the levels of asymmetric dimethylarginine, the only independent and changeable parameter of atherosclerosis, in early period would prevent the development of early and accelerated atherosclerosis, hence increased morbidity and mortality.Key words: Chronic renal disease, atherosclerosis, nitric oxide, asymmetric dimethylarginineAsymmetric dimethylarginine may play an important role in early-accelerated atherosclerosis development in patients with chronic renal disease. Our study aimed to define the role of asymmetric dimethylarginine in atherosclerosis development in 32 healthy controls and 65 patients with chronic renal disease.Intima and media thickness of carotid artery were found to be significantly (p=0.0004) increased in patients compared to controls, indicating existence of atherosclerosis. Patient age (r=0.619; p<0.001), malondialdehyde (r=0.434; p=0.005), C-reactive protein (r=0.482; p<0.003), systolic blood pressure (r=0.402; p=0.009), waist/hip ratio (r=0.377; p=0.015), diastolic blood pressure (r=0.332; p=0.034), ADMA (r=0.320; p<0.041), homocysteine (r=0.335; p=0.043), urinary protein excretion (r=0.308; p=0.049) were positively and total nitrite/serum creatinine ratio was (-r=0.415; p=0.011) negatively correlated with intima and media thickness of carotid artery. In multivariate analysis only patient age (p=0.00007) and plasma asymmetric dimethylarginine level (p=0.03) were found to be independent predictors of intima and media thickness of carotid artery. Increase of each one year in patient age and 1 ?mol/L plasma asymmetric dimethylarginine level resulted an increase of 0.011 (0.06-0.16) mm and 0.336 (0.035-0.637) mm in intima and media thickness of carotid artery independent of other factors, respectively.In our patients e-selectin (r=0.376; p=0.004), C-reactive protein (r=0.335; p=0.012), homocysteine (r=0.305; p=0.022) ve MDA (r=0.282; p=0.025) were positively and arginine/ asymmetric dimethylarginine (-r=0.573; p=0.001) ratio and total nitrit/serum creatinine ratio (-r=0.362; p=0.006) were negatively correlated with asymmetric dimethylarginine levels. But multivariate analysis revealed that only C-reactive protein (p=0.002) was found to be an independent predictor of increased asymmetric dimethylarginine level and each increase of 1 mg/dL in C-reactive protein level resulted in 0.1 mm increase of intima and media thickness of carotid artery.In conclusion, we showed that patient age and plasma asymmetric dimethylarginine level were independent predictors of atherosclerosis development. We also revealed that decreased metabolism as a result of inflammation could be responsible for increased plasma asymmetric dimethylarginine levels in our patients. Our results suggest that therapies aiming to decrease the levels of asymmetric dimethylarginine, the only independent and changeable parameter of atherosclerosis, in early period would prevent the development of early and accelerated atherosclerosis, hence increased morbidity and mortality.