Anemia sering terjadi pada bayi prematur, ditandai oleh penurunan nilai hematokrit,retikulosit dan kadar eritropoetin endogen rendah. Di Amerika Serikat, 60-80% bayiberat lahir sangat rendah (BBLSR) ...mengalami anemia dan membutuhkan transfusi seldarah merah berulang sehingga mempunyai risiko terjadi komplikasi penularan penyakit.Salah satu upaya menurunkan kebutuhan transfusi tersebut dengan pemberianeritropoetin eksogen yaitu recombinant human eritropoietin (r-HU EPO) yang berfungsimerangsang proliferasi, diferensiasi dan maturasi sel darah merah dalam sumsum tulang.Walaupun pada bayi prematur dijumpai kadar eritropoetin yang sangat rendah, namunprogenitor eritroid tetap sensitif terhadap eritropoetin eksogen. Pemberian r-HU EPOdapat meningkatkan eritropoesis sehingga bermanfaat mengurangi kebutuhan transfusipada anemia bayi prematur. Pemberian dalam dosis cukup pada usia dini, suplementasipreparat besi dan protein mempunyai efektifitas yang baik. Berbagai penelitian terhadappenggunaan r-HU EPO pada anemia bayi prematur telah dilakukan tetapi belum adakesepakatan mengenai protokol pemberian, termasuk waktu, dosis, cara, dan durasipemberian.
Eritropoetin merupakan molekul glikoprotein yang terdiri dari 165 asam amino dan 4 gugus karbohidratdengan berat molekul sekitar 34 k dalton. Peran eritropoetin dalam produksi sel darah merah ...melaluimeningkatkan survival, proliferasi dan diferensiasi dari progenitor eritroid pada sumsum tulang. Eritropoetinberikatan dengan reseptor selanjutnya terjadi aktivasi ras/mitogen intraselular yang berperan dalam proliferasisel. Regulasi produksi eritropoetin adalah peran dari hypoxia-inducible transcription factor-1 (HIF-1). Padabayi yang lahir prematur terjadi penurunan kadar Hb yang berlebihan dibandingkan dengan bayi cukupbulan. Banyak faktor yang mempengaruhi anemia prematuritas, salah satu di antaranya adalah kurang responeritropoetin terhadap penurunan kadar Hb. Penggunaan eritropoetin rekombinan mengurangi frekuensitransfusi darah dan meningkatkan retikulosit dengan cepat. Eritropoetin rekombinan belum merupakanstandar pengobatan anemia prematuritas secara universal
Anemia in patient with chronic kidney disease could cause a lot of complication. The first line therapy of this condition is by treating with erythropoiesis-stimulating agents (ESA) or called ...erythropoietin. The erythropoietin alpha and beta were two types of the human recombinant erythropoietin that are usually used in Indonesia. The aim of this study was to determine the effectivity of erythropoietin alpha compared to erythropoietin beta especially in haemoglobin and haematocrit level. This prospective observational study was conducted in March – September 2016. The inclusion criteria were CKD stage 5 patients with a minimum of 3 months of regular hemodialysis, Hb <10 g/dL with enough iron status ST > 20% and FS > 200ng/mL. The methology of this study had been approved by the Health Research Ethics Committee of the Bhayangkara H.S. Samsoeri Mertojoso Hospital, Surabaya. Patients received 2000 IU subcutaneous erythropoietin twice a week on both groups. Blood sample was withdrawn in pre-treatment and after 4 weeks of post erythropoietin therapy treatment for measurement of haemoglobin and haematocrit. Target for this erythropoietin therapy are increase of Hb 0.5 – 1.5 g/dL (not to exceed 12 g/dL) and increase of Hct level 2 – 4 % in 4 weeks. Based on the inclusion criteria, there were 20 patients in this study (10 patient each of both erythropoietin alpha either beta group) that consist of 7 women and 13 men. After the treatment, the mean of increased haemoglobin level for erythropoietin alpha group was 1.28 ± 0.80 g/dL (p=0.001) and erythropoietin beta was 0.37 ± 0.95 g/dL (p=0.254). The mean of increased haematocrit level for erytropoietin alpha group was 3.56 ± 3.46 % (p=0.010) and erythropoietin beta was 1.34 ± 2.71 % (p=0.152). In comparison of haemoglobin and haematocrit achievement in both groups showed that erythropoietin alpha gave better achievement in haemoglobin parameter (p=0.033), but there were no differences in both groups on haematocrit parameters (p=0.127).
Latar belakang. Pasien sindrom nefrotik resisten steroid mengalami hipoeritropoetinemia akibat kehilangan eritropoetin melalui urin dan gangguan pembentukan eritropoetin oleh ginjal. Paparan albumin ...kronis bersifat toksik dan menginduksi apoptosis sel tubulus ginjal, sementara eritropoetin diproduksi oleh sel peritubular ginjal. Tujuan. Menentukan hubungan kadar albumin serum dengan eritropoetin serum pada pasien sindrom nefrotik resisten steroid anak. Metode. Penelitian cross-sectional dilaksanakan pada pasien sindrom nefrotik anak resisten steroid dari bulan Agustus–Desember 2013 di unit rawat jalan dan rawat inap RS Dr. Hasan Sadikin, Bandung. Kadar albumin serum diperiksa dengan metoda turbidimetri dan kadar eritropoetin serum dengan metode ELISA. Analisis korelasi kadar albumin dengan eritropoetin serum dilakukan dengan menggunakan uji Rank Spearman. Hasil. Sembilan belas anak memenuhi kriteria penelitian, 14 subjek laki - laki, dan 5 perempuan dengan usia 3–13 tahun. Nilai laju filtrasi glomerulus rerata 147,8+75 ml/menit/1,73 m2, sementara kadar hemoglobin 12,1+2,8 g/dL. Nilai median albumin serum 3,8 (0,9–4,6)g/dL dan median eritropoetin serum 7,2 (0,2–39,6) mIU/mL. Tidak terdapat korelasi antara albumin dan eritropoetin serum pada sindrom nefrotik anak resisten steroid (rs=0,123;p=0,615). Kesimpulan. Kadar albumin serum tidak berhubungan dengan kadar eritropoetin serum pada pasien sindrom nefrotik resisten steroid anak.
Aim: The efficacy of erythropoietin (EPO) on wound healing has been shown before. There islimited data about the efficacy of EPO on fracture healing. In this study, the efficacy of EPO onclosed ...forearm fracture healing is searched by an experimental model. Material and method: Twenty eight rats were picked randomly and divided into EPO andControl groups. On the first day, fracture was performed on the right ulna and radius of all rats.500 U/kg daily low dose EPO was administered for each rat in EPO group and the same volumeof isotonic sodium chloride solution was given intraperitoneally in the control group for fivedays. Seven rats from each group were sacrificed at the end of the first week; the others weresacrificed at the end of the third week. Results: At the end of the first week and third week, bone healing scores of EPO group issignificantly higher than the control group according to the histological, clinic and radiologicanalysis. Conclusion: EPO could have positive effects on healing of forearm fracture on rats in acuteand subacute period. Low dose EPO may be a new protective agent against delayed union ornonunion in the risk population to go or not to go to surgical treatment
Giriş: Eritropoetin’in yara iyileşmesi üzerine olan etkisi daha önce gösterilmiştir. Kırıkiyileşmesi üzerine olan etkisi üzerine sınırlı sayıda bilgi mevcuttur. Bu çalışmada eritropoetininkapalı kırık iyileşmesi üzerine olan etkileri deneysel bir model kullanılarak araştırılmıştır.Yöntem: Yirmisekiz rat alınıp rastgele sçilerek Eritropoetin ve Kontrol grupları oluşturuldu.Çalışmanın ilk gününde tüm ratların sağ önkollarında kapalı ulna ve radius cisim kırıklarıoluşturuldu. Beş gün boyunca Eritropoetin grubundaki ratlarda 500 U/kg düşük doz eritropoetinintraperitoneal olarak verilirken; Kontrol grubundaki ratlarda ise aynı hacimde izotonikintraperitoneal olarak verildi. Gruplardaki yedişer det rat ilk hafta sonunda, kalan yedişer adetratda üçüncü haftanın sonunda sakrifiye edildi.Bulgular: Birinci ve üçüncü hafta sonunda kırık iyileşme skorları histolojik, radyolojik ve klinikolarak değerlendirildiğinde Eritropoetin grubunda Kontrol grubuna gore belirgin olarak dahayüksek olduğu saptandı.Sonuç: Ratların kapalı önkol kırıklarının iyileşmesi üzerine akut ve subakut peryottaeritropoetinin pozitif etkileri olabilir. Düşük doz eritropoetin kullanımı cerrahiye gidecek veyagitmeyecek olan riskli hasta gruplarında kaynama gecikmesi veya kaynamamaya karşı koruyucuajan olarak verilebilir
Abstract
Objective
Erythropoietin (EPO) is widely used for treatment of anemia associated with different diseases; however, its adverse effects limit its use in clinical practice. Therefore, ...understanding the effects of EPO at the molecular and cellular level is crucial to adjust treatment regimes, and to develop non-hematopoietic EPO derivatives. In this study, we used a proteomics approach to identify how EPO treatment modifies the cellular proteome.
Methods
SH-SY5Y neuroblastoma cells were used as the model system to analyze the effects of EPO treatment at different time points (24 h and 48 h). Proteomic analysis revealed changes in 74 proteins after EPO treatment. Following proteomics analysis, Reactome pathway analysis were carried out to identify the affected cellular pathways.
Results
According to results, EPO alters the levels of 74 protein species (40 were increased, 34 were decreased). The levels of 35 proteins were changed by 24 h EPO incubation, whereas 17 protein species were altered by 48 h EPO incubation. Levels of 22 protein species were altered by both of the incubation periods (24 h and 48 h).
Conclusion
Overall, our results suggest that EPO mainly affects protein species in glucose metabolism, protein and RNA metabolism, cytoskeletal proteins, and mitochondrial protein species.
Amaç: Bu çalışmada diyaliz uygulanan çocuklarda ortalama trombosit hacmi (OTH) ve eritropoetin (EPO) kullanımı arasındaki ilişkinin incelenmesi amaçlanmıştır. Yöntemler: Çalışmada 16 hemodiyaliz ...(HD), 20 periton diyalizi (PD) olmak üzere 36 hastanın eritropoetin öncesi ve sonrası OTH değerleri retrospektif olarak incelendi. Hastalar haftalık eritropoetin alımı 150 Ü/kg\'ın altında (düşük EPO) ve 150 Ü/kg üzerinde (yüksek EPO) olmak üzere 2 gruba ayrıldı. Hastaların yaşları, vücut ağırlıkları, kronik böbrek yetmezliğine neden olan primer hastalıkları, uygulanan diyaliz tedavi yöntemleri, EPO dozları kaydedildi. EPO başlanmadan önce ve başlandıktan 4 hafta sonra alınan kan örneklerinde tam kan sayımı (hemogram) yapılarak OTH değerleri kaydedildi.. Bulgular: Hemodiyaliz grubunun EPO sonrası OTH değerlerinde EPO öncesi OTH değerlerine göre anlamlı yükselme (8,18±1,52 fL ve 9,20±1,46 fL, p=0,046) saptanırken, PD grubunda ise EPO sonrası değerlerde yükselme olmasına rağmen, fark istatistiksel anlamlılık sınırına çok yakın bulundu (8,28±1,80 fL ve 9,39±1,50 fL, p=0,051). Yüksek dozda EPO alan HD hastalarında EPO sonrası OTH değerleri artmış olarak bulundu (7,81 ± 1,04 ve 9,61 ± 1,05 fL; p=0,06). Düşük doz EPO kullananlarda ise farklılık görülmedi (8,64 ± 1,97 ve 8,67 ± 1,81 fL; p>0,05). PD hastalarında ise EPO dozu OTH değerleri üzerinde etkili bulunmadı (9,57 ± 1,58 ve 9,10 ± 1,42 fL; p>0,05). Sonuç: HD uygulanan çocuklarda EPO\'nun OTH düzeylerini etkilediği, ancak PD hastalarında OTH düzeylerinin EPO tedavisinden etkilenmediği görüldü. Hekimler tromboz riski yüksek hastalarda yüksek doz EPO kullanırken dikkatli olmalıdır.
Objective: In this study, it was aimed to determine the relationship between erythropoietin (EPO) use and mean platelet volume (MPV) in the children undergoing dialysis. Methods: MPV values before and after EPO use in 36 patients (16 hemodialysis - HD, 20 peritoneal dialysis - PD) were retrospectively evaluated. Patients were divided into two groups according to weekly EPO need as; given less than 150 U/kg defined as low EPO and more than 150 U/kg as high EPO groups. The age, weight, primary cause of chronic renal failure, dialysis methods and EPO dosages of patients were recorded. Blood samples were taken before and 4 weeks after EPO usage and MPV values were noted from complete blood counts. Results: While significant increase was seen in the MPV values after EPO in comparison to MPV values before EPO in the HD group (8.18±1.52 fL vs. 9.20±1.46 fL; p=0.046); near significant difference was found in the MPV levels after EPO (8.28±1.80 fL vs. 9.39±1.50 fL; p=0,051) in PD group. In HD patients when high dose of EPO was given, MPV levels were found to be significantly elevated (7.81 ± 1.04 vs 9.61 ± 1.05; p=0.06) after EPO. However, no difference was seen with the lowe dose EPO subgroup (8.64 ± 1.97 ve 8.67 ± 1.81; p>0,05). No effect of EPO dose was found on MPV values in PD patients (9.57 ± 1.58 ve 9.1 ± 1.42; p>0.05). Conclusion: It was observed that EPO influenced MPV values in children undergoing HD, while no effect of erythropoietin was found on MPV values of PD patients. Physicians should be careful while using high dose erythropoietin in children with high thrombosis risk. J Clin Exp Invest 2014; 5 (3): 415-419
Cilj rada: Ocjena oralnog inhibitora prolil-hidroksilaze hipoksijom induciranog faktora roksadustata za liječenje anemije povezane s kroničnom bubrežnom bolešću (KBB). Metode: U ovom su se ...randomiziranom, otvorenom, aktivnim lijekom kontroliranom ispitivanju faze 3 uspoređivali roksadustat i darbepoetin alfa (DA) u bolesnika s anemijom i KBB-om neovisnih o dijalizi tijekom razdoblja od ≤ 104 tjedna. Doze lijeka titrirale su se da bi se razina hemoglobina (Hb) korigirala i održala u rasponu od 10,0 do 12,0 g/dl. Primarna mjera ishoda bio je odgovor Hb-a u cjelovitom skupu podataka za analizu, koji se defi nirao kao Hb ≥ 11,0 g/dl i promjena početne vrijednosti Hb-a za ≥ 1,0 g/dl u bolesnika kojima je početni Hb iznosio > 8,0 g/dl odnosno promjena početne vrijednosti Hb-a za ≥ 2,0 g/dl u bolesnika kojima je početni Hb bio ≤ 8,0 g/dl tijekom prva 24 tjedna liječenja bez primjene dodatne terapije za postizanje zadovoljavajuće razine hemoglobina (rescue) (granica neinferiornosti: 15 %). Ključne sekundarne mjere ishoda uključivale su promjenu vrijednosti lipoproteina male gustoće (LDL), vrijeme do prve intravenske (i.v.) primjene željeza, promjenu srednjeg arterijskog tlaka i vrijeme do pojave hipertenzije. U ispitivanju su se ocjenjivale i nuspojave. Rezultati: Od 616 randomiziranih bolesnika (roksadustat: 323; DA: 293) 424 dovršilo je liječenje (roksadustat: 215; DA: 209). Odgovor Hb-a zabilježen uz roksadustat bio je neinferioran onome opaženome uz DA roksadustat: 256/286 (89,5 %) u odnosu na DA: 213/273 (78,0 %); razlika: 11,51 %; interval pouzdanosti od 95 %: 5,66 - 17,36 %. Roksadustat je održao vrijednosti Hb-a tijekom razdoblja do 2 godine. Roksadustat je bio neinferioran u odnosu na DA s obzirom na promjenu srednjeg arterijskog tlaka i vrijeme do nastupa hipertenzije, a superioran s obzirom na promjenu vrijednosti LDL-a i vrijeme do prve i.v. primjene željeza. Obje su skupine imale usporedive sigurnosne profi le. Rezultati pokazuju da nije bilo razlike između skupina s obzirom na kompozitne mjere ishoda, koje su uključivale velike kardiovaskularne štetne događaje (MACE) i MACE+ MACE: 0,81 (0,52 - 1,25), P=0,339; MACE+: 0,90 (0,61 - 1,32), P=0,583. Zaključak: Roksadustat je prihvatljiva opcija za liječenje anemije u bolesnika s KBB om neovisnih o dijalizi, koja omogućuje održane razine Hb-a tijekom razdoblja do 104 tjedna.
Bubrežna anemija nastaje kao posljedica kronične bubrežne bolesti (KBB). Incidencija se povećava s napredovanjem KBB. Cilj rada je informiranje obiteljskih liječnika o najnovijim spoznajama i ...načinima aktivnijeg pristupa anemiji kronične bubrežne bolesti, sukladnim s nacionalnim smjernicama. Pretražene su elektroničke baze podataka PubMed i Cochrane Datebase of Systematic Reviews radi dohvaćanja retrospektivnih studija koje su objavljene između 1996. i 2015. godine
korištenjem ključnih riječi po MeSH-u “anemia”, “chronic renal insuffi ciency”, “erythropoietin” i “primary health care”. Dodatno su ručno pretražene reference svih dostupnih relevantnih članaka i udžbenika. Primjena lijekova za stimulaciju eritropoeze (LSE) usporava progresiju KBB, smanjuje potrebu za transfuzijama krvi i poboljšava kvalitetu života. Ciljna koncentracija hemoglobina (Hb) koju valja trajno održavati je 110-120 g/L. Veća razina Hb povezana je s većom smrtnosti bolesnika na dijalizi i pojavnosti većih kardiovaskularnih incidenata. Ovisno o stupnju kronične bolesti (predijalizna, dijalizirana populacija), dobi, prisutnom riziku, početno i održavajuće liječenje kao i ciljnu razinu hemoglobina treba strogo individualizirati. Zaključuje se da rano prepoznavanje i primjereni ispravak anemije primjenom LSE koristi bolesnicima s KBB. Ciljna koncentracija Hb koju valja trajno održavati je 110-120 g/L. Sustavnom provedbom primarne i sekundarne prevencije, uz edukaciju i implementaciju stručnih nacionalnih smjernica u svakodnevni rad liječnika obiteljske medicine, može se poboljšati zdravstvena skrb bolesnika koji boluju od KBB.
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