Hemodiyaliz hastalarında sol ventrikül hipertrofisine etki eden faktörler; otonom nöropatinin rolü
The factors affecting left ventricular hypertrophy in haemodialysis patients; the effect of autonomic neuropathy
Yazar: LÜTFİYE DEMİR
Danışman: PROF. DR. ALAATTİN YILDIZ
İstanbul Üniversitesi / Tıp Fakültesi / Dahili Tıp Bilimleri Bölümü / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2008
Konu: Nefroloji = Nephrology

Özet:
Hemodiyalize giren üremik hastaların büyük bir çoğunluğunda, hipertansiyon ve sol ventrikül hipertrofisi görülmektedir. Bunun sebebi, üreminin yol açtığı direkt toksisite nedeniyle üremik miyokardın oluşması ve fonksiyonlarının kötüleşmesi (ürenin kardiyak depresör özelliği, kalb kasındaki metabolizmanın bozulması ve sol ventrikül dilatasyonuna yol açması) olduğu gibi, kronik böbrek yetersizliğinde görülen pek çok metabolik, biyokimyasal, hormonal ve hemodinamik özellikler de olabilir. Kronik böbrek yetersizliği hastalarında üremik nöropatinin bir komponenti olarak otonom fonksiyon bozukluğu önceden beri bilinmektedir. Otonom sistem disfonksiyonu hemodiyaliz hastalarında, klinik olarak diyaliz sırasında hipotansiyon atakları, terleme bozuklukları, ortostatik hipotansiyon, erkeklerde impotans ile kendini göstermektedir. Otonom nöropati tanısında kardiyovasküler refleks testlerin yerini, kantitatif olması ve sempatik-parasempatik sistemi ayrı değerlendirmesi nedeniyle, son zamanlarda kalb hızı değişkenliğinin (KHD) spektral ve nonspektral analiz yöntemi almıştır.Bu çalışmada, hemodiyaliz hastalarında görülen sol ventrikül hipertrofisine etki eden diğer faktörlerin yanında üremik otonom nöropatinin etkisini incelemeyi amaçladık. Kronik hemodiyaliz programında izlenen, diyabetes mellitus, dilate kardiyomiyopati, iskemik kalp hastalığı ve konjestif kalp yetersizliği olmayan, 20-65 yaş arasındaki 42 hasta incelendi. Hastaların erkek ve kadın cinsiyet dağılımı eşit olup (E=21, K=21), ortalama yaş 44± 12 yıl idi. 19 hastanın son dönem böbrek yetersizliği nedeni bilinmiyordu. 7 hasta kronik glomerülonefrit, 6 hasta kronik pyelonefrit, 4 hasta VUR nefropatisi, 2 hasta primer nefroskleroz, 1 hasta polikistik böbrek hastalığı, 1 hasta herediter nefrit, 1 hasta herediter nefrit + VUR nefropatisi, 1 hasta HELLP tanısı ile izlenmekte idi. Hastaların sol ventrikül hipertrofisi tanısı, ekokardiyografik olarak bakılan SVKİ (sol ventrikül kitle indeksi)'e göre konuldu. Otonom nöropati ise holter verilerine göre kalb hızı değişkenliği spektral ve non-spektral analizi ile değerlendirildi. Sabah 07.00- gece 22.00 arası gündüz, gece 22.00- sabah 07.00 arası değerler gece parametreleri olarak kabul edildi.Kalb hızı değişkenliği parametreleri , biyokimyasal parametreler, sol ventrikül hipertrofisi olan ve olmayan grupta ayrı ayrı incelendi. CRP ve sedimentasyon değerleri SVH (sol ventrikül hipertrofisi) olan grupta, olmayan gruba göre anlamlı olarak yüksek bulundu. Hemoglobin değerleri arasında iki grup arasında anlamlı fark görülmedi ve korelasyon analizinde, Hb ile sol ventrikül hipertrofisi arasında korelasyon saptanmadı. Kalb hızı değişkenliği parametreleri, tüm hemodiyaliz hastalarında normal kişilerin değerine göre düşük düzeyde saptandı. Tüm KHD parametreleri ve sol ventrikül kitle indeksi arasında negatif korelasyon saptandı. Hastaların gece-gündüz ritmi değerlendirmesinde tüm hastalarda gündüz LF değeri gece LF değerine göre düşük saptandı; bu da gündüz olması gereken sempatik tonusün, tüm hemodiyaliz hastalarında bozulmuş olduğunu gösterdi. Yine bu bulgularla uyumlu olarak , gündüz LF/HF, gece LF/HF'e göre anlamlı şekilde düşük saptandı; buna rağmen LF/HF oranı tüm hastalarda normal sınırlar içinde (1-2 arasında) seyretti (Bu hem sempatik hem de parasempatik hasarın olması ile ilgili olarak düşünüldü). HF'de azalma olmakla birlikte, gece HF değeri gündüz HF değerine göre yüksek saptandı. Çok değişkenli lineer regresyon analizinde sol ventrikül kitle indeksi ile en güçlü ilişkiyi gösteren parametrelerin, rMSSD, yaş, CRP ve sistolik kan basıncı olduğu görüldü.Sonuç olarak, hemodiyaliz hastalarının %70'nde sol ventrikül hipertrofisi saptanmıştır. Yaş ve sistolik kan basıncı arttıkça sol ventrikül kitle indeksi de artmaktadır. Sol ventrikül kitle artışı ile inflamasyon ilişkilidir. Hastalarda hem sempatik sistemi hem de parasempatik sistemi etkileyen otonom nöropati mevcuttur. Her iki sistemin hasarı da sol ventrikül kitle artışı ile bağlantılı bulunmuştur. Ancak sol ventrikül kitle artışı ile en güçlü bağlantı, parasempatik sistemdeki hasarın göstergesi olan rMSSD ile bulunmuştur.SUMMARYMost patients with renal failure taking hemodialysis treatment are diagnosed with hypertension and left ventricular hypertrophy. Formation of uremic myocardium caused by direct toxicity and functionality abnormalities (cardiac depressor effect of uremia, deterioration of myocard metabolism and left ventricular dilatation) as well as the metabolic, biochemical, hormonal and hemodinamic symptoms seen during the chronic renal failure can be the causes for this situation. Autonomic system dysfunction had been known to be a component of uremic neuropathy in patients with renal failure. The autonomic system dysfunction is clinically seen as hypotension attacks, respiration abnormalities, ortostatic hypotension, impotence (for male patients) during hemodialysis in uremic patients. Spectral and non-spectral analysis of heart rate variability (HRV) method replaced the cardiovascular reflex tests. Because HRV is cantitative and evaluates the sympathetic and parasympathetic systems separately.This study investigated whether the left ventricular hypertrophy is affected by autonomic neuropathy or not on hemodialysis patients besides the other factors. Fourthy two patients aged between 20 and 65 who were being monitored on hemodialysis program are examined. The patients did not have diabetes mellitus, dilated cardiomyopathy, ischemic heart disease or congestive heart failure. Sex distribution were equal (21 men, 21 women). The average age were 44±12 years. Etiology of renal failure for 19 patients were unknown. The other patients had the following diagnosis: 7 patients with chronic glomerulonephritis , 6 patients with chronic pyelonephritis, 4 patients with VUR nephropathy, 2 patients with primary nephrosclerosis, 1 patient with polycystic kidney disease, 1 patient with hereditary nephritis, 1 patient with hereditary nephritis + VUR nephropathy and 1 patient with HELLP. Left ventricular hypertrophy were diagnosed on the patients based on the echochardiographic left ventricular mass index (LVMI). Autonomic neuropathy were evaluated based on the spectral and non-spectral analysis of holter data. Daily data between 7:00 a.m. and 10:00 p.m. are used as day-time values while the data between 10:00 p.m. and 7:00 a.m. are used as the night-time values.Heart rate variability parameters and biochemical parameters are examined separately on patients with left ventricular hypertrophy and patients without left ventricular hypertrophy. CRP( C-reactive protein ) and sedimentation values were found to be significantly higher on patients with LVH ( Left Ventricular Hypertrophy ) compared to the patients without the disease. No significant difference were detected on the hemoglobin values between the two group of patients and no correlation were found between hemoglobin and left ventricular hypertrophy during the correlation analysis. Heart rate variability parameters are found to be lower than the normal people on all hemodialysis patients. A negative correlation is found between all HRV parameters and left ventricular mass index. Day-time LF value is found to be lower than the night LF value for all patients during the night-day rythm evaluation and this shows that the sympathetic tonus that should be seen during the day is deteriorated on all patients. In accordance with these findings, day-time LF/HF is found to be significantly lower than night-time LF/HF; although LF/HF ratio were between normal ranges ( between 1-2 ) on all patients during the study (this is related to the existence of both sympathetic and parasympathetic detriment). HF value decreased for all patients, although night-time HF value is found to be higher than day HF value. It is seen that the rMSSD, age, CRP and systolic blood pressure parameters had the strongest relation to the left ventricular index during the multiple parameter linear regression analysis.As a conclusion, 70% of hemodialysis patients are diagnosed with left ventricular hypertrophy. As the age and systolic blood pressure increase, the left ventricular mass index also increases. Inflammation and left ventricular mass increase are related. Autonomic neuropathy affecting both sympathetic and the parasympathetic system is seen on the hemodialysis patients. Damage on both systems are found to be related to the left ventricular mass increase. But strongest relation to the left ventricular mass increase is found to the rMSSD, which is also an indicator of the damage on the parasympathetic system.

Abstract:
Most patients with renal failure taking hemodialysis treatment are diagnosed with hypertension and left ventricular hypertrophy. Formation of uremic myocardium caused by direct toxicity and functionality abnormalities (cardiac depressor effect of uremia, deterioration of myocard metabolism and left ventricular dilatation) as well as the metabolic, biochemical, hormonal and hemodinamic symptoms seen during the chronic renal failure can be the causes for this situation. Autonomic system dysfunction had been known to be a component of uremic neuropathy in patients with renal failure. The autonomic system dysfunction is clinically seen as hypotension attacks, respiration abnormalities, ortostatic hypotension, impotence (for male patients) during hemodialysis in uremic patients. Spectral and non-spectral analysis of heart rate variability (HRV) method replaced the cardiovascular reflex tests. Because HRV is cantitative and evaluates the sympathetic and parasympathetic systems separately.This study investigated whether the left ventricular hypertrophy is affected by autonomic neuropathy or not on hemodialysis patients besides the other factors. Fourthy two patients aged between 20 and 65 who were being monitored on hemodialysis program are examined. The patients did not have diabetes mellitus, dilated cardiomyopathy, ischemic heart disease or congestive heart failure. Sex distribution were equal (21 men, 21 women). The average age were 44±12 years. Etiology of renal failure for 19 patients were unknown. The other patients had the following diagnosis: 7 patients with chronic glomerulonephritis , 6 patients with chronic pyelonephritis, 4 patients with VUR nephropathy, 2 patients with primary nephrosclerosis, 1 patient with polycystic kidney disease, 1 patient with hereditary nephritis, 1 patient with hereditary nephritis + VUR nephropathy and 1 patient with HELLP. Left ventricular hypertrophy were diagnosed on the patients based on the echochardiographic left ventricular mass index (LVMI). Autonomic neuropathy were evaluated based on the spectral and non-spectral analysis of holter data. Daily data between 7:00 a.m. and 10:00 p.m. are used as day-time values while the data between 10:00 p.m. and 7:00 a.m. are used as the night-time values.Heart rate variability parameters and biochemical parameters are examined separately on patients with left ventricular hypertrophy and patients without left ventricular hypertrophy. CRP( C-reactive protein ) and sedimentation values were found to be significantly higher on patients with LVH ( Left Ventricular Hypertrophy ) compared to the patients without the disease. No significant difference were detected on the hemoglobin values between the two group of patients and no correlation were found between hemoglobin and left ventricular hypertrophy during the correlation analysis. Heart rate variability parameters are found to be lower than the normal people on all hemodialysis patients. A negative correlation is found between all HRV parameters and left ventricular mass index. Day-time LF value is found to be lower than the night LF value for all patients during the night-day rythm evaluation and this shows that the sympathetic tonus that should be seen during the day is deteriorated on all patients. In accordance with these findings, day-time LF/HF is found to be significantly lower than night-time LF/HF; although LF/HF ratio were between normal ranges ( between 1-2 ) on all patients during the study (this is related to the existence of both sympathetic and parasympathetic detriment). HF value decreased for all patients, although night-time HF value is found to be higher than day HF value. It is seen that the rMSSD, age, CRP and systolic blood pressure parameters had the strongest relation to the left ventricular index during the multiple parameter linear regression analysis.As a conclusion, 70% of hemodialysis patients are diagnosed with left ventricular hypertrophy. As the age and systolic blood pressure increase, the left ventricular mass index also increases. Inflammation and left ventricular mass increase are related. Autonomic neuropathy affecting both sympathetic and the parasympathetic system is seen on the hemodialysis patients. Damage on both systems are found to be related to the left ventricular mass increase. But strongest relation to the left ventricular mass increase is found to the rMSSD, which is also an indicator of the damage on the parasympathetic system.SUMMARYMost patients with renal failure taking hemodialysis treatment are diagnosed with hypertension and left ventricular hypertrophy. Formation of uremic myocardium caused by direct toxicity and functionality abnormalities (cardiac depressor effect of uremia, deterioration of myocard metabolism and left ventricular dilatation) as well as the metabolic, biochemical, hormonal and hemodinamic symptoms seen during the chronic renal failure can be the causes for this situation. Autonomic system dysfunction had been known to be a component of uremic neuropathy in patients with renal failure. The autonomic system dysfunction is clinically seen as hypotension attacks, respiration abnormalities, ortostatic hypotension, impotence (for male patients) during hemodialysis in uremic patients. Spectral and non-spectral analysis of heart rate variability (HRV) method replaced the cardiovascular reflex tests. Because HRV is cantitative and evaluates the sympathetic and parasympathetic systems separately.This study investigated whether the left ventricular hypertrophy is affected by autonomic neuropathy or not on hemodialysis patients besides the other factors. Fourthy two patients aged between 20 and 65 who were being monitored on hemodialysis program are examined. The patients did not have diabetes mellitus, dilated cardiomyopathy, ischemic heart disease or congestive heart failure. Sex distribution were equal (21 men, 21 women). The average age were 44±12 years. Etiology of renal failure for 19 patients were unknown. The other patients had the following diagnosis: 7 patients with chronic glomerulonephritis , 6 patients with chronic pyelonephritis, 4 patients with VUR nephropathy, 2 patients with primary nephrosclerosis, 1 patient with polycystic kidney disease, 1 patient with hereditary nephritis, 1 patient with hereditary nephritis + VUR nephropathy and 1 patient with HELLP. Left ventricular hypertrophy were diagnosed on the patients based on the echochardiographic left ventricular mass index (LVMI). Autonomic neuropathy were evaluated based on the spectral and non-spectral analysis of holter data. Daily data between 7:00 a.m. and 10:00 p.m. are used as day-time values while the data between 10:00 p.m. and 7:00 a.m. are used as the night-time values.Heart rate variability parameters and biochemical parameters are examined separately on patients with left ventricular hypertrophy and patients without left ventricular hypertrophy. CRP( C-reactive protein ) and sedimentation values were found to be significantly higher on patients with LVH ( Left Ventricular Hypertrophy ) compared to the patients without the disease. No significant difference were detected on the hemoglobin values between the two group of patients and no correlation were found between hemoglobin and left ventricular hypertrophy during the correlation analysis. Heart rate variability parameters are found to be lower than the normal people on all hemodialysis patients. A negative correlation is found between all HRV parameters and left ventricular mass index. Day-time LF value is found to be lower than the night LF value for all patients during the night-day rythm evaluation and this shows that the sympathetic tonus that should be seen during the day is deteriorated on all patients. In accordance with these findings, day-time LF/HF is found to be significantly lower than night-time LF/HF; although LF/HF ratio were between normal ranges ( between 1-2 ) on all patients during the study (this is related to the existence of both sympathetic and parasympathetic detriment). HF value decreased for all patients, although night-time HF value is found to be higher than day HF value. It is seen that the rMSSD, age, CRP and systolic blood pressure parameters had the strongest relation to the left ventricular index during the multiple parameter linear regression analysis.As a conclusion, 70% of hemodialysis patients are diagnosed with left ventricular hypertrophy. As the age and systolic blood pressure increase, the left ventricular mass index also increases. Inflammation and left ventricular mass increase are related. Autonomic neuropathy affecting both sympathetic and the parasympathetic system is seen on the hemodialysis patients. Damage on both systems are found to be related to the left ventricular mass increase. But strongest relation to the left ventricular mass increase is found to the rMSSD, which is also an indicator of the damage on the parasympathetic system.