Eritropoetin Uygulanan Hemodiyaliz Hastalarında Gelişen Fonksiyonel Demir Eksikliğinin sTfR ve RetHbC Ölçümleriyle Erken Dönemde Saptanması ve Eritropoetin Rezistansı
Öz
Giriş: Hemodiyaliz hastalarında rHuEPO uygulaması fonksiyonel demir eksikliğine neden olmaktadır. Klasik demir eksikliğini gösteren parametreler, fonksiyonel demir eksikliğini tanımlamada yetersiz kalmaktadır. Biz bu sebeple rHuEPO uygulanan hemodiyaliz hastalarında sTfR ve RetHbC ölçümleri ile demir eksikliğinin erken dönemde saptanmasında, yararlı olup olamayacağını göstermeye çalıştık.
Yöntem: Çalışma grubumuzdaki olguların 54’ ünde hemodiyaliz uygulanıyordu. Bunlardan 21’ i IV demir kullanmakta idi, 33’ü ise demir kullanmıyordu. Kontrol grupları olarak, demir eksikliği anemisi grubu (n=16) ve sağlıklı kontrol grubu (n=10) kişiden oluşturuldu. Olgularda tam kan sayımı ile birlikte Retikülosit hemoglobin içeriği RetHbC), serum demiri, serum demir bağlama kapasitesi, Ferritin, Transferrin, serum transferrin reseptörü (sTfR) düzeyleri ve sTfR/log ferritin değerlerini saptadık.
Bulgular: Diyaliz hastalarının ortalama sTfR, ferritin, SDBK ve Retikülosit değerlerinin sağlıklı kontrol grubundan belirgin şekilde yüksek olduğu (p<0,001), SD değerinin farklı olmadığı (p>0,005), RetHbC ve %TSI değerlerinin ise belirgin şekilde daha düşük olduğu bulunmuştur (p<0,001). Diyaliz hastaları içinde demir tedavisi alan hastalarla almayanların değerleri karşılaştırıldığında; demir tedavisi alan diyaliz hastaları grubunun ortalama SD, SDBK ve %TSI değerlerinin demir tedavisi almayan diyaliz hastaları grubundan belirgin şekilde yüksek olduğu (p<0,001), ferritin, Ret ve RetHbC değerinin farklı olmadığı (p>0,05), sTfR değerlerinin ise belirgin şekilde daha düşük olduğu bulunmuştur (p<0,001). Diyaliz hastaları ile demir eksikliği anemisi bulunan kontrol olgularının değerleri karşılaştırıldığında; diyaliz hastaları grubunun ortalama ferritin, SD, Ret, RetHbC ve %TSI değerlerinin demir eksikliği anemili kontrol grubundan belirgin şekilde yüksek olduğu (p<0,001), sTfR değerinin farklı olmadığı (p>0,005), SDBK değerlerinin ise belirgin şekilde daha düşük olduğu bulunmuştur (p<0,001).
Sonuç: sTfR seviyeleri yalnızca rHuEPO tedavisi uygulanan hemodiyaliz hastalarında normalin 3 kati kadar artmaktadır. IV demir ile birlikte rHuEPO tedavisi uygu- andığı zaman sTfR düzeyleri azalmaktadır. STfR’nin hemodiyaliz uygulanan hastalarda, demir eksikliği anemisini en erken ve en doğru olarak tanımlamasında diğer klasik hematolojik parametrelerden daha değerli bilgiler verdiği görülmüştür. EPO uygulamasını takiben 3. günde toplanan kan örneklerinde, rHuEPO’nun kemik iliği stimülasyonu sonucu sTfR seviyelerinde bir artışa yol açtığı düşünülmektedir. RetHbC ölçümlerinin ise EPO uygulamasını takiben dolaşıma çıkan erken retikülositlerin hemoglobinizasyonunu göstermekte olup, fonksiyonel demir eksikliyi anemisi düşünülen olgularda IV demir uygulamasını takiben kemik iliğinin oluşturduğu cevabin erken dönemde değerlendirilmesinde yardımcı bir parametre olarak kullanılabileceği düşünülmektedir.
Anahtar Kelimeler
Kaynakça
- Watson A. Iron management during treatment with recombinant human erythro poietin in chronic renal failure. J. Clin. Pharmacol, 33(12):1134–1138, Dec 1993.
- I. C. Macdougall. Poor response to erythropoietin: practical guidelines on investigation and management. Nephrology Dialysis Transplantation, 10:607–614, 1995.
- S. Fishbane et all Iron management in end-stage renal disease. Amer- ican Journal of Kidney Diseases, 29:319–333, 1997.
- Weiss G. Iron and anemia of chronic disease. Kidney Int, 55:S12–S17, 1999.
- J. W. Eschbach et all. Iron overload in renal failure patients: changes since the introduction of erythropoietin therapy. Kidney International, 55:S35–S43, 1999.
- B. J. Ferguson and B. S. Skikne. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. Journal of Clinical Laboratory Medicine, 119:385–389, 1992.
- Punnonen K, et all.. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood, 89:1052–1057, 1997.
- Zanen AL, et all. Over saturation of transferrin after intravenous ferric gluconate (ferrlecit) in haemodialysis patients. Nephrol Dial Transplant, 11:820–824, 1996.
- C. Brugnara, et all. Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. American Journal of Clinical Pathology, 108:133–142, 1997.
- S. Fishbane, et all . Reticulocyte hemoglobin content in the evaluation of iron status of hemodialysis patients. Kidney International, 52:217–222, 1997.
- I. C. Macdougall. Monitoring of iron status and iron supplementation in pa- tients treated with erythropoietin. Current Opinion in Nephrology and Hypertension, 3:620–625, 1994.
- K. Kalantar-Zadeh, M. Kleiner, E. Dunne, K. Ahern, M. Nelson, and R. Koslowe. To- tal iron-binding capacity estimated transferrin correlates with the nutritional sub- jective global assessment in hemodialysis patients. American Journal of Kidney Dis- eases, 31:263–272, 1998.
- Tarng DC, et all. Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. Kidney Int, 55:S107–S118, 1999.
- I. C. Macdougall. Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin. Nephrology Dialysis Transplantation, 13:23– 27, 1998.
- Taylor JE, Peat N, Porter C, and Morgan AG. Regular, low-dose intravenous iron therapy improves response to erythropoietin in haemodialysis patients. Nephrol Dial Transplant, 11:1079–1083, 1996.
- Silverberg DS, et all. Intravenous iron supplementation for the treat- ment of the anemia of moderate to severe chronic renal failure patients not receiv- ing dialysis. Am J Kidney Dis, 27:234–238, 1996.
- J. Kletzmayr, M. Födinger, J. Kovarik, G. SunderPlassmann, and W. H. Hörl. Serum transferrin receptor and transferrin receptor/log ferritin index predicting response to erythropoietin and intravenous iron therapy in hemodialysis patients. page 26, May 1999.
- S. Bhandari, J. H. Turney, A. M. Brownjohn, and D. Norfolk. Reticulocyte indices in patients with endstage renal disease on hemodialysis. Journal of Nephr NFK-DOQI clinical practice guidelines for the treatment of anemia of chronic re-nal failure III. Iron support. Am. J. Kidney Diseases, 30(Suppl3):S202–S212, 1997ology, 11:78–82, 1998.
- B. J. Ferguson and B. S. Skikne. Serum transferin receptor distinguishes the ane- mia of chronic disease from iron deficiency anemia. Journal of Clinical Laboratory Medicine, 119:385–389, 1992. Weiss G, Houston T, Kastner S, Johrer K, Grunewald K, and Brock JH. Regulation of cellular iron metabolism by erythropoietin: activation of ironregulatory pro- tein and up-regulation of transferin receptor expression in erythroid cells. Blood, 89:680–687, 1997
- M. Buttarello, P. Bulian, A. Venudo, and P. Rizzotti. Laboratory evaluation of the miles h-3 automated reticulocyte counter: a comparative study with manual reference method and sysmex r-1000. Archives of Pathology and Laboratory Medicine, 119:1141–1148, 1995.
- NFK-DOQI clinical practice guidelines for the treatment of anemia of chronic re-nal failure III. Iron support. Am. J. Kidney Diseases, 30(Suppl3):S202–S212, 1997
- N. Ahluwalia, et all. Markers of masked iron deficiency and effectiveness of epo therapy in chronic renal failure. American Journal of Kidney Diseases, 30(4):532–541, October 1997
- Skikne B, Ahluwalia N, Fergusson B, Chonko A, and Cook J. Effects of recombinant human erythropoietin on iron absorption in chronic renal failure. Blood, 92:24B, 1998.
- E. Alan Mast, M. A. Blinder, Qing Lu, Sherri Flax, and Dennis J. Dietzen. Clinical utility of the diagnosis of iron deficiency. Blood, 99(4):1489–1491, 2002.
- E. L. Mast and M. A. Blinder. Clinical utility of the soluble transferin receptor and comparison with serum ferritin in several populations. Clinical Chemistry, 44:45– 51, 1998
Early Detection of Functional Iron Deficiency in Hemodialysis Patients Treated with Erythropoietin Using sTfR and RetHbC Measurements and Erythropoietin Resistance
Öz
Introduction: The administration of rHuEPO in hemodialysis patients leads to functional iron deficiency. Classic parameters for diagnosing iron deficiency are insufficient for identifying functional iron deficiency. Therefore, we aimed to evaluate whether measuring sTfR and RetHbC could be useful in detecting iron deficiency at an early stage in hemodialysis patients receiving rHuEPO treatment.
Methods: Among the cases in our study group, 54 patients were undergoing hemodialysis. Of these, 21 were receiving IV iron, and 33 were not. Control groups were formed from individuals with iron deficiency anemia (n=16) and healthy controls (n=10). In the study, complete blood counts were performed, and levels of reticulocyte hemoglobin content (RetHbC), serum iron, serum total iron-binding capacity (TIBC), ferritin, transferrin, serum transferrin receptor (sTfR), and sTfR/log ferritin were measured.
Results: The mean levels of sTfR, ferritin, TIBC, and reticulocyte values in dialysis patients were significantly higher than those of the healthy control group (p<0.001), while the standard deviation (SD) values did not differ significantly (p>0.005). RetHbC and %TSI values were found to be significantly lower (p<0.001). When comparing dialysis patients receiving iron therapy with those not receiving iron therapy, the mean SD, TIBC, and %TSI values of the group receiving iron therapy were significantly higher than those not receiving iron therapy (p<0.001), while ferritin, Ret, and RetHbC values did not differ significantly (p>0.05). However, the sTfR levels in the group receiving iron therapy were significantly lower (p<0.001). When comparing dialysis patients with the control group of individuals with iron deficiency anemia, the mean values of ferritin, SD, Ret, RetHbC, and %TSI in the dialysis patient group were significantly higher (p<0.001), while the sTfR values did not differ significantly (p>0.005). The SDBK values were significantly lower in dialysis patients (p<0.001).
Conclusion: sTfR levels increase up to three times higher than normal in hemodialysis patients who are treated with rHuEPO. When rHuEPO therapy is combined with IV iron, sTfR levels decrease. It has been observed that sTfR provides more valuable information than other classic hematological parameters for the earliest and most accurate diagnosis of iron deficiency anemia in hemodialysis patients. It is suggested that sTfR levels rise due to bone marrow stimulation after EPO administration, especially on the third day following blood sampling. RetHbC measurements reflect the hemoglobinization of early reticulocytes that enter circulation following EPO administration. Therefore, RetHbC can be used as an auxiliary parameter to assess the early response of bone marrow after IV iron treatment in cases with suspected functional iron deficiency anemia.
Anahtar Kelimeler
Kaynakça
- Watson A. Iron management during treatment with recombinant human erythro poietin in chronic renal failure. J. Clin. Pharmacol, 33(12):1134–1138, Dec 1993.
- I. C. Macdougall. Poor response to erythropoietin: practical guidelines on investigation and management. Nephrology Dialysis Transplantation, 10:607–614, 1995.
- S. Fishbane et all Iron management in end-stage renal disease. Amer- ican Journal of Kidney Diseases, 29:319–333, 1997.
- Weiss G. Iron and anemia of chronic disease. Kidney Int, 55:S12–S17, 1999.
- J. W. Eschbach et all. Iron overload in renal failure patients: changes since the introduction of erythropoietin therapy. Kidney International, 55:S35–S43, 1999.
- B. J. Ferguson and B. S. Skikne. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. Journal of Clinical Laboratory Medicine, 119:385–389, 1992.
- Punnonen K, et all.. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood, 89:1052–1057, 1997.
- Zanen AL, et all. Over saturation of transferrin after intravenous ferric gluconate (ferrlecit) in haemodialysis patients. Nephrol Dial Transplant, 11:820–824, 1996.
- C. Brugnara, et all. Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. American Journal of Clinical Pathology, 108:133–142, 1997.
- S. Fishbane, et all . Reticulocyte hemoglobin content in the evaluation of iron status of hemodialysis patients. Kidney International, 52:217–222, 1997.
- I. C. Macdougall. Monitoring of iron status and iron supplementation in pa- tients treated with erythropoietin. Current Opinion in Nephrology and Hypertension, 3:620–625, 1994.
- K. Kalantar-Zadeh, M. Kleiner, E. Dunne, K. Ahern, M. Nelson, and R. Koslowe. To- tal iron-binding capacity estimated transferrin correlates with the nutritional sub- jective global assessment in hemodialysis patients. American Journal of Kidney Dis- eases, 31:263–272, 1998.
- Tarng DC, et all. Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. Kidney Int, 55:S107–S118, 1999.
- I. C. Macdougall. Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin. Nephrology Dialysis Transplantation, 13:23– 27, 1998.
- Taylor JE, Peat N, Porter C, and Morgan AG. Regular, low-dose intravenous iron therapy improves response to erythropoietin in haemodialysis patients. Nephrol Dial Transplant, 11:1079–1083, 1996.
- Silverberg DS, et all. Intravenous iron supplementation for the treat- ment of the anemia of moderate to severe chronic renal failure patients not receiv- ing dialysis. Am J Kidney Dis, 27:234–238, 1996.
- J. Kletzmayr, M. Födinger, J. Kovarik, G. SunderPlassmann, and W. H. Hörl. Serum transferrin receptor and transferrin receptor/log ferritin index predicting response to erythropoietin and intravenous iron therapy in hemodialysis patients. page 26, May 1999.
- S. Bhandari, J. H. Turney, A. M. Brownjohn, and D. Norfolk. Reticulocyte indices in patients with endstage renal disease on hemodialysis. Journal of Nephr NFK-DOQI clinical practice guidelines for the treatment of anemia of chronic re-nal failure III. Iron support. Am. J. Kidney Diseases, 30(Suppl3):S202–S212, 1997ology, 11:78–82, 1998.
- B. J. Ferguson and B. S. Skikne. Serum transferin receptor distinguishes the ane- mia of chronic disease from iron deficiency anemia. Journal of Clinical Laboratory Medicine, 119:385–389, 1992. Weiss G, Houston T, Kastner S, Johrer K, Grunewald K, and Brock JH. Regulation of cellular iron metabolism by erythropoietin: activation of ironregulatory pro- tein and up-regulation of transferin receptor expression in erythroid cells. Blood, 89:680–687, 1997
- M. Buttarello, P. Bulian, A. Venudo, and P. Rizzotti. Laboratory evaluation of the miles h-3 automated reticulocyte counter: a comparative study with manual reference method and sysmex r-1000. Archives of Pathology and Laboratory Medicine, 119:1141–1148, 1995.
- NFK-DOQI clinical practice guidelines for the treatment of anemia of chronic re-nal failure III. Iron support. Am. J. Kidney Diseases, 30(Suppl3):S202–S212, 1997
- N. Ahluwalia, et all. Markers of masked iron deficiency and effectiveness of epo therapy in chronic renal failure. American Journal of Kidney Diseases, 30(4):532–541, October 1997
- Skikne B, Ahluwalia N, Fergusson B, Chonko A, and Cook J. Effects of recombinant human erythropoietin on iron absorption in chronic renal failure. Blood, 92:24B, 1998.
- E. Alan Mast, M. A. Blinder, Qing Lu, Sherri Flax, and Dennis J. Dietzen. Clinical utility of the diagnosis of iron deficiency. Blood, 99(4):1489–1491, 2002.
- E. L. Mast and M. A. Blinder. Clinical utility of the soluble transferin receptor and comparison with serum ferritin in several populations. Clinical Chemistry, 44:45– 51, 1998
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Hematoloji, Nefroloji |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 29 Nisan 2025 |
| Gönderilme Tarihi | 5 Mart 2025 |
| Kabul Tarihi | 26 Mart 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 5 Sayı: 1 |
e-ISSN: 2791-9935