Hemodiyaliz hastalarında eritroferon, hepsidin düzeyleri ve demir parametrelerinin ilişkisinin araştırılması
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Tarih
2022
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Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş: Anemi, kronik böbrek hastalığı (KBH) hastalarında çok sık görülen önemli bir sorundur ve en önemli nedeni eritropoetin (EPO) düzeyinde göreceli düşüklük olmakla beraber; anemiye katkıda bulunan mutlak demir eksikliği, inflamasyon ve hepsidin artışı gibi birçok faktör vardır. Yakın zamanda EPO uyarısı sonrası eritroblastlardan salınan bir protein olarak tanımlanmış eritroferonun (ERFE) hepsidin salınımını baskıladığını ileri süren çalışmalar mevcuttur. Çalışmamızda eritroferon, hepsidin, eritropoetin düzeyleri ve demir parametrelerini epoetin alfa ve darbopoetin olmak üzere iki farklı eritropoez stimüle edici ajan (ESA) alan ve ESA almayan hemodiyaliz hastalarında araştırmayı ve tedavi alan hastalarda ESA uygulanmasını takiben bu parametrelerin zaman içindeki değişimlerini incelemeyi hedefledik. Gereç ve Yöntem: Prospektif olarak yapılan çalışmamızda, hemodiyalize giren 60 hasta ESA almayanlar, epoetin alfa alanlar ve darbepoetin alfa alanlar olmak üzere 3 gruba ayrılarak iki aşamada incelenmiştir. İlk aşamada bu üç grupta hepsidin ve ERFE düzeyleri ile demografik veriler, KBH etyolojisi, diyaliz süresi, hemogram, demir parametreleri, EPO düzeyleri arasındaki ilişki araştırılmıştır. İkinci aşamada yalnızca ESA kullanan hastalarla incelemeye devam edilmiş ve bu hastalarda ESA uygulanmasından hemen önce, 2. ve 7. günde hemodiyaliz öncesinde tekrar kanlar alınarak başta EPO, hepsidin ve ERFE düzeylerindeki değişim ve bu düzeylerin birbirleriyle, hemogram ve demir parametreleri ile olan ilişkisi ortaya konulmaya çalışılmıştır. Bulgular: Hasta grupları yaş, cinsiyet, KBH süresi, hemodiyalize girme süresi, böbrek fonksiyonları, hemogram ve demir parametreleri açısından benzerdi ancak C- reaktif protein (CRP) düzeyi epoetin alfa grubunda diğer gruplardan daha yüksekti. Hepsidin ve ERFE düzeyleri açısından da gruplar arasında anlamlı fark yoktu. EPO düzeyi beklendiği gibi ESA almayan grupta düşüktü, diğer iki grupta benzerdi. ESA uygulamasını takiben yapılan incelemelerde EPO düzeyinin her iki grupta sayısal olarak 2. günde arttığı, 7. günde tekrar azalarak benzer bazal seviyelere indiği gözlenmekle beraber bu değişim yalnızca epoetin alfa grubunda istatistiksel anlamlı idi (<0,001). Hepsidin düzeyinin 2. günde ve 7. günde sayısal olarak giderek arttığı görülmekle birlikte bu değişim epoetin grubunda istatistiksel anlamlı olup hepsidinin 2. gündeki artışı darbepoetin grubunda istatistiksel anlamlılığa ulaşmadı (epoetin grubunda 0, 2, 7.gün sırasıyla 5,7, 6,18, 7,54 ng\ml, p<0,001; darbepoetin grubunda sırasıyla 5,3, 6,75, 8,01 ng\ml, p=0,006). ERFE düzeyleri de sayısal olarak artma eğiliminde gözükmekle birlikte bu artış istatistiksel anlamlılığa ulaşmıyordu (epoetin grubunda 0, 2, 7.gün sırası ile 0,62, 0,64, 0,73 ng\ml, p=0,072; darbepoetin grubunda sırasıyla 0,5, 0,51, 0,89 ng\ml, p=0,069). Hem hepsidin hem ERFE düzeyleri 0, 2, 7. gün değerleri gruplar arasında farklı değildi. Sonuç: Hayvan çalışmaları ve diğer hasta gruplarında yapılan çalışmalarda endojen ve eksojen EPO uyarısı ile arttığı öne sürülmüş olan ERFE düzeyleri, bizim çalışmamızda ESA almayan ve farklı ESA'lar alan hemodiyaliz hastalarında benzer bulunmuştur. Yine ERFE ile baskılandığı düşünülen hepsidin düzeyi açısından çalışmamızda gruplar arasında fark saptanmamıştır ancak ESA uygulamasından sonra hepsidin düzeyleri özellikle bazal CRP' nin yüksek olduğu epoetin grubunda daha anlamlı olmak üzere progresif artış göstermiştir. Son dönem KBH hastalarında eritropoeze etki eden çok sayıda faktör ve karmaşık mekanizmaları yansıtır şekilde, bu hasta grubunda az sayıda olan ERFE çalışmalarında çelişkili sonuçlar bildirmektedir. Bizim çalışmamızda ESA sonrası ERFE düzeyleri çok dar bir aralıkta değişim göstermiştir ve her iki grupta da bir artış trendi izlemekle birlikte istatistiksel anlamlılığa ulaşmamıştır. ERFE' nin artışı ile hepsidinin ilk günlerdeki artış miktarı arasında anlamlı ve negatif yönde korelasyon saptanması çalışmanın kısmen küçük hasta sayısı ve ardışık ölçümlerin az sayıda olması gibi kısıtlılıkları nedeniyle net ortaya konamamış bir ilişki olabileceğini düşündürmektedir. Anahtar Kelimeler: Kronik böbrek hastalığı, hemodiyaliz, anemi, eritropoez stimüle edici ajanlar, eritropoetin, hepsidin, eritroferon
Introduction: Anemia is a major problem in chronic kidney disease (CKD) patients. The most important reason is the relative low erythropoietin (EPO) level however here are many factors that contribute to anemia, such as absolute iron deficiency, inflammation, and increased hepcidin. There are studies suggesting that erythroferron (ERFE), a protein released from erythroblasts after EPO stimulation, suppresses hepcidin release. In our study, we aimed to investigate erythroferron, hepcidin, erythropoietin levels and iron parameters in hemodialysis patients who received two different erythropoiesis stimulating agents (ESA), as epoetin alpha and darbopoetin alpha compared to patients who were not given ESA. We also aimed to examine the changes in these parameters over time following ESA administration in patients receiving treatment. Material and Method: In our prospective study, 60 patients undergoing hemodialysis were classified into 3 groups, those who did not receive ESA, those who received epoetin alpha and those who received darbepoetin alpha, and were examined in two stages. In the first stage, the relationship between hepcidin and ERFE levels and demographic data, CKD etiology, dialysis time, hemogram, iron parameters, and EPO levels were investigated in these three groups. In the second stage, the investigation continued with patients using only ESA. In these patients, blood samples were taken again just before ESA administration and on the 2nd and 7th days before hemodialysis. The change in EPO, hepcidin and ERFE levels and the relationship of these levels with each other, hemogram and iron parameters were tried to be revealed. Results: The patient groups were similar in terms of age, gender, CKD duration, duration of hemodialysis, kidney functions, hemogram and iron parameters, but C-reactive protein (CRP) level was higher in the epoetin alfa group than in the other groups. There was no significant difference between the groups in terms of hepcidin and ERFE levels. EPO level was lower in the group that did not receive ESA, as expected, and in the other two groups it was similar. In the evolvation performed after the ESA application, it was observed that the EPO level increased numerically in both groups on the 2nd day, and decreased again on the 7th day and decreased to similar basal levels, but this change was statistically significant only in the epoetin alfa group (<0.001). Although it was observed that the level of hepcidin increased gradually on the 2nd and 7th days, this change was statistically significant in the epoetin group, and the increase in hepcidin on the 2nd day did not reach statistical significance in the darbepoetin group (0, 2, and 7th day in the epoetin group, respectively, 5,7, 6.18, 7,54 ng\ml, p<0.001; and in the darbepoetin group, respectively, 5,3, 6,75, 8,01 ng\ml, p=0.006). Although ERFE levels were also tended to increase numerically, this increase did not reach statistical significance (in the epoetin group, 0, 2 and 7 days, respectively, 0,62, 0,64, 0,73 ng\ml, p=0.072; in the darbepoetin group, respectively, 0,5, 0,51, 0,89 ng\ml, p=0,069). Both hepcidin and ERFE levels at day 0, 2, and 7 were not different between groups. Conclusion: ERFE levels, which were suggested to increase with endogenous and exogenous EPO stimulation in animal studies and studies conducted in other patient groups, were found to be similar across groups in hemodialysis patients who did not receive ESA and who received different ESAs in our study. Again, no difference was found between the groups in terms of hepcidin level, which is thought to be suppressed by ERFE, but after ESA administration, hepcidin levels increased progressively, especially in the epoetin group, where basal CRP was high. As reflecting the multiple factors and complex mechanisms affecting erythropoiesis in end-stage CKD patients, the few ERFE studies in this patient group report conflicting results. In our study, ERFE levels changed in a very narrow range after ESA and although an increasing trend was observed in both groups, it did not reach statistical significance. The significant and negative correlation between the increase in ERFE and the amount of increase in hepcidin in the first days suggests that there may be a relationship that could not be clearly revealed due to the limitations of the study, such as the small number of patients and the small number of consecutive measurements. Keywords: Chronic kidney disease, hemodialysis, anemia, erythropoiesis stimulating agents, erythropoietin, hepcidin, erythroferrone
Introduction: Anemia is a major problem in chronic kidney disease (CKD) patients. The most important reason is the relative low erythropoietin (EPO) level however here are many factors that contribute to anemia, such as absolute iron deficiency, inflammation, and increased hepcidin. There are studies suggesting that erythroferron (ERFE), a protein released from erythroblasts after EPO stimulation, suppresses hepcidin release. In our study, we aimed to investigate erythroferron, hepcidin, erythropoietin levels and iron parameters in hemodialysis patients who received two different erythropoiesis stimulating agents (ESA), as epoetin alpha and darbopoetin alpha compared to patients who were not given ESA. We also aimed to examine the changes in these parameters over time following ESA administration in patients receiving treatment. Material and Method: In our prospective study, 60 patients undergoing hemodialysis were classified into 3 groups, those who did not receive ESA, those who received epoetin alpha and those who received darbepoetin alpha, and were examined in two stages. In the first stage, the relationship between hepcidin and ERFE levels and demographic data, CKD etiology, dialysis time, hemogram, iron parameters, and EPO levels were investigated in these three groups. In the second stage, the investigation continued with patients using only ESA. In these patients, blood samples were taken again just before ESA administration and on the 2nd and 7th days before hemodialysis. The change in EPO, hepcidin and ERFE levels and the relationship of these levels with each other, hemogram and iron parameters were tried to be revealed. Results: The patient groups were similar in terms of age, gender, CKD duration, duration of hemodialysis, kidney functions, hemogram and iron parameters, but C-reactive protein (CRP) level was higher in the epoetin alfa group than in the other groups. There was no significant difference between the groups in terms of hepcidin and ERFE levels. EPO level was lower in the group that did not receive ESA, as expected, and in the other two groups it was similar. In the evolvation performed after the ESA application, it was observed that the EPO level increased numerically in both groups on the 2nd day, and decreased again on the 7th day and decreased to similar basal levels, but this change was statistically significant only in the epoetin alfa group (<0.001). Although it was observed that the level of hepcidin increased gradually on the 2nd and 7th days, this change was statistically significant in the epoetin group, and the increase in hepcidin on the 2nd day did not reach statistical significance in the darbepoetin group (0, 2, and 7th day in the epoetin group, respectively, 5,7, 6.18, 7,54 ng\ml, p<0.001; and in the darbepoetin group, respectively, 5,3, 6,75, 8,01 ng\ml, p=0.006). Although ERFE levels were also tended to increase numerically, this increase did not reach statistical significance (in the epoetin group, 0, 2 and 7 days, respectively, 0,62, 0,64, 0,73 ng\ml, p=0.072; in the darbepoetin group, respectively, 0,5, 0,51, 0,89 ng\ml, p=0,069). Both hepcidin and ERFE levels at day 0, 2, and 7 were not different between groups. Conclusion: ERFE levels, which were suggested to increase with endogenous and exogenous EPO stimulation in animal studies and studies conducted in other patient groups, were found to be similar across groups in hemodialysis patients who did not receive ESA and who received different ESAs in our study. Again, no difference was found between the groups in terms of hepcidin level, which is thought to be suppressed by ERFE, but after ESA administration, hepcidin levels increased progressively, especially in the epoetin group, where basal CRP was high. As reflecting the multiple factors and complex mechanisms affecting erythropoiesis in end-stage CKD patients, the few ERFE studies in this patient group report conflicting results. In our study, ERFE levels changed in a very narrow range after ESA and although an increasing trend was observed in both groups, it did not reach statistical significance. The significant and negative correlation between the increase in ERFE and the amount of increase in hepcidin in the first days suggests that there may be a relationship that could not be clearly revealed due to the limitations of the study, such as the small number of patients and the small number of consecutive measurements. Keywords: Chronic kidney disease, hemodialysis, anemia, erythropoiesis stimulating agents, erythropoietin, hepcidin, erythroferrone
Açıklama
Anahtar Kelimeler
Kronik böbrek hastalığı, hemodiyaliz, anemi, eritropoez stimüle edici ajanlar, eritropoetin, hepsidin, eritroferon, Chronic kidney disease, hemodialysis, anemia, erythropoiesis stimulating agents, erythropoietin, hepcidin, erythroferrone, Hematoloji, Hematology
