Abstract
Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m2) between September 2021 and February 2022. There were no drug-related complications, except for a patient who had a headache and hot flash, resulting in discontinuation of HIF-PH inhibitor at 3 months. Among 10 patients who continued HIF-PH inhibitors for over 3 months, hemoglobin levels increased significantly (median from 9.6 g/dL to 10.7 g/dL, p = 0.004) and hepcidin-25 levels tended to decrease (median from 11.5 ng/mL to 3.0 ng/mL, p = 0.294) at 3-month follow-up. In conclusion, HIF-PH inhibitors might be safe and effective for the treatment of renal anemia in patients with chronic heart failure.
References
Anand IS, Gupta P (2018) Anemia and iron deficiency in heart failure: current concepts and emerging therapies. Circulation 138(1):80–98
Anand IS (2008) Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 52(7):501–511
van der Meer P, Voors AA, Lipsic E, Smilde TD, van Gilst WH, van Veldhuisen DJ (2004) Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 44(1):63–67
Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, Maggioni AP, McMurray JJ, O’Connor C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ (2013) Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 368(13):1210–1219
Gupta N, Wish JB (2017) Hypoxia-inducible factor prolyl hydroxylase inhibitors: a potential new treatment for anemia in patients with CKD. Am J Kidney Dis 69(6):815–826
Eleuteri E, Di Stefano A, Giordano A, Corra U, Tarro Genta F, Gnemmi I, Giannuzzi P (2016) Prognostic value of angiopoietin-2 in patients with chronic heart failure. Int J Cardiol 212:364–368
Poss J, Ukena C, Kindermann I, Ehrlich P, Fuernau G, Ewen S, Mahfoud F, Kriechbaum S, Bohm M, Link A (2015) Angiopoietin-2 and outcome in patients with acute decompensated heart failure. Clin Res Cardiol 104(5):380–387
Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L (2013) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 62(5):849–859
Ganz T (2011) Hepcidin and iron regulation, 10 years later. Blood 117(17):4425–4433
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113(9):1271–1276
Gupta J, Mitra N, Kanetsky PA, Devaney J, Wing MR, Reilly M, Shah VO, Balakrishnan VS, Guzman NJ, Girndt M, Periera BG, Feldman HI, Kusek JW, Joffe MM, Raj DS (2012) Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephrol 7(12):1938–1946
Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL (2001) Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 103(16):2055–2059
von Haehling S, Anker SD (2011) Cardio-renal anemia syndrome. Contrib Nephrol 171:266–273
Kurata Y, Tanaka T, Nangaku M (2020) Hypoxia-inducible factor prolyl hydroxylase inhibitor in the treatment of anemia in chronic kidney disease. Curr Opin Nephrol Hypertens 29(4):414–422
Palazzuoli A, Silverberg DS, Iovine F, Calabrò A, Campagna MS, Gallotta M, Nuti R (2007) Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. Am Heart J 154(4):645.e9–15
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Nakamura, M., Imamura, T., Sobajima, M. et al. Initial experience of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with heart failure and renal anemia. Heart Vessels 38, 284–290 (2023). https://doi.org/10.1007/s00380-022-02181-1
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DOI: https://doi.org/10.1007/s00380-022-02181-1