ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -12 مورد

Cardiovascular and renal effects of anemia in chronic kidney disease

Cardiovascular and renal effects of anemia in chronic kidney disease
Author:
Jeffrey S Berns, MD
Section Editors:
Steve J Schwab, MD, FACP, FASN
Gary C Curhan, MD, ScD
Deputy Editor:
Eric N Taylor, MD, MSc, FASN
Literature review current through: Apr 2025. | This topic last updated: Jun 11, 2024.

INTRODUCTION — 

Anemia is common among patients with chronic kidney disease (CKD). In addition to causing symptoms, severe anemia may affect cardiovascular function in nondialysis CKD and dialysis patients. Among nondialysis CKD patients, severe anemia may be associated with more rapid progression of CKD, including to end-stage kidney disease (ESKD).

This topic reviews the effects of anemia on cardiovascular dysfunction, particularly left ventricular hypertrophy (LVH) and heart failure (HF), and on the progression of kidney dysfunction in CKD patients.

Other signs and symptoms of anemia (which are the same in CKD patients as among individuals without kidney disease) are discussed elsewhere. (See "Diagnostic approach to anemia in adults", section on 'Correlation with symptoms'.)

The treatment of anemia for patients with CKD and for patients with heart failure is discussed elsewhere. (See "Treatment of anemia in nondialysis chronic kidney disease" and "Treatment of anemia in patients on dialysis" and "Evaluation and management of anemia and iron deficiency in adults with heart failure".)

CARDIOVASCULAR — 

Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD, including those undergoing maintenance dialysis [1]. Even patients with mild CKD have a greater burden of prevalent cardiovascular disease compared with similar age controls [2]. (See "Chronic kidney disease and coronary heart disease" and "Overview of diagnosis of heart disease in patients on dialysis".)

Severe anemia is an important, independent risk factor for the development and progression of left ventricular hypertrophy (LVH) and heart failure (HF) and of adverse cardiovascular outcomes, including mortality [3-5]. Many of the studies of patients with CKD that reported associations between anemia and adverse outcomes were conducted in prior eras when severe anemia was much more common. However, even in more recent studies, anemia among patients with CKD is associated with more HF hospitalizations and more rapid CKD progression [6].

We discuss here the contribution of anemia to LVH, HF, and mortality in end-stage kidney disease (ESKD) patients, as well as effects of treatment with erythropoiesis-stimulating agents (ESAs) on LVH and HF. However, this information is not used to determine indications or goals of treatment with ESAs. Instead, randomized trials examining clinical outcomes among patients treated with ESAs are used to determine indications and goals of treatment. These data are discussed elsewhere. (See "Treatment of anemia in nondialysis chronic kidney disease", section on 'Erythropoiesis-stimulating agents' and "Treatment of anemia in patients on dialysis", section on 'Erythropoiesis-stimulating agents (ESAs)'.)

Left ventricular hypertrophy — LVH is a major risk factor for cardiovascular morbidity and mortality in patients with ESKD [7,8]. LVH is common among patients with ESKD or near ESKD, with a reported prevalence of up to 75 percent [9-11].

Role of anemia — Anemia has been identified as a risk factor for the development of LVH in patients on dialysis and in patients with nondialysis CKD [3-5,12-14]. In an observational study including 432 hemodialysis and peritoneal dialysis patients, anemia was independently associated with an increase in left ventricular mass index [13]. In an analysis of data from the Atherosclerosis Risk in Communities Study (ARIC), among nondialysis CKD patients, anemia was predictive of left ventricular diameter after adjusting for kidney function and blood pressure [5].

Pathophysiology — Potential mechanisms that may explain the relationship between anemia and the development of LVH among CKD patients include [15-19]:

●Effects of reduced oxygen delivery to the myocardium, perhaps leading to increased myocyte necrosis and apoptosis

●Anemia-related increased cardiac output and reduced systemic vascular resistance

●Increased oxidative stress

●Activation of the sympathetic nervous system

Effect of anemia treatment on LVH — The treatment of severe anemia with ESAs is associated with improvement of left ventricular hypertrophy (LVH). The best data are from a 2009 meta-analysis of 15 studies including 1731 patients [20]. Among patients with baseline severe anemia (defined as hemoglobin [Hb] levels <10 g/dL with mean baseline Hb levels as low as 5.9 g/dL in individual studies), ESA treatment to increase Hb levels to ≤12 g/dL was associated with significant reductions in left ventricular mass index (-32.7 g/m2, 95% CI -49.4 to -16.1). The treatment of moderate anemia (ie, Hb ≥10 g/dL) to either Hb levels >12 g/dL or ≤12 g/dL was not associated with significant changes in the left ventricular mass index. In another study of patients with CKD and Hb <10 g/dL who were treated with ESAs, patients with a Hb target between 11.0 to 13.0 g/dL had greater reductions in left ventricular mass index than patients with a Hb target between 9.0 to 11.0 g/dL [21].

Whether the regression of LVH in CKD patients who are treated for severe anemia is associated with improved cardiac outcomes has not been well studied. Any such analysis may be confounded by other factors that affect outcomes, such as ESA-induced increases in blood pressure and LVH geometry [22].

One small study of patients with anemia and CKD suggested that compared with ESA therapy, treatment with the HIF-PHI roxadustat may lead to greater LVH regression [23]. Further studies will be necessary to determine the relative effects of ESA and HIF-PHI therapies on LVH.

Heart failure

Role of anemia in patients with heart failure — Severe anemia and CKD are independent risk factors for the development of HF [3-5,24]. In an observational study of 22,720 patients with CKD (of which 23 percent had anemia), those with anemia had higher rates of hospitalizations for heart failure (1.6 versus 0.8 per 100 patient-years) and higher rates of 40 percent or greater loss of estimated glomerular filtration rate (eGFR) (18.1 versus 7.3 per 100 patient-years) compared with those without anemia [6].

Effect of treatment of anemia on heart failure — Uncontrolled studies, none very recent, have described improvement in the clinical manifestations of HF after prolonged treatment of anemia in CKD patients [25-28]. As an example, in one study of 126 CKD patients with HF, an increase in the mean Hb level from 10.3 to 13.1 g/dL (with intravenous iron and ESAs) over a mean period of 12 months was associated with a rise in the mean left ventricular ejection fraction (33 to 40 percent), falls in the mean New York Heart Association (NYHA) class (3.8 to 2.7), and number of hospitalizations (3.7/patient to 0.2/patient) [26]. An index of fatigue and shortness of breath also fell significantly. Similar results were noted in another uncontrolled study that included 179 CKD patients with severe HF studied over a mean of nearly 12 months [27].

A systematic review of nine randomized trials of ESAs in HF, not all specifically in patients with CKD, concluded that anemia treatment improved exercise duration and capacity, ejection fraction, NYHA class, quality-of-life indicators, and HF-related hospitalizations [29]. Another meta-analysis of randomized, controlled trials found that ESA treatment improved dyspnea and NYHA class; there was no significant improvement in mortality or hospitalization, but there was increased risk of thromboembolic events [30]. Consistent with this are results of a large, randomized, double-blind trial of over 2000 patients with systolic HF and anemia to receive either darbepoetin alfa to achieve a target Hb of 13 g/dL or placebo. The was no difference in the primary outcome, which was a composite of death from any cause or hospitalization for worsening HF, but there was an increase in thromboembolic events and a nonsignificant increase in strokes [31]. An absence of clinical benefit among HF patients was also reported in the smaller Study of Anemia in Heart Failure (STAMINA-HeFT) trial comparing darbepoetin and placebo [32]. A 2017 update of cardiology society guidelines recommended against use of ESAs in patients with HF and anemia [33]. Increased morbidity and/or mortality has been associated with attaining normal or near-normal Hb levels with ESAs. (See "Treatment of anemia in nondialysis chronic kidney disease", section on 'Target hemoglobin value'.)

Treating iron deficiency, independent of anemia, has also been studied in patients with heart failure, many of whom also have some degree of CKD [34,35]. In the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial, for example, a proactive iron dosing strategy resulted in a 34 percent lower relative risk of heart failure hospitalization compared with a low-dose, reactive strategy, despite similar hemoglobin concentrations in the two groups [36]. Further studies are needed to better understand the impact of iron deficiency and its treatment in patients with CKD and heart failure.

Coronary heart disease — Exercise-mediated cardiac ischemia is also ameliorated with partial correction of severe anemia.

Mortality — Anemia is an important, independent risk for mortality [3-5]. In one study of 432 dialysis patients with a mean baseline Hb level of 8.8 g/dL, after adjusting for age, diabetes, ischemic heart disease, blood pressure, and serum albumin, each 1 g/dL lower Hb was associated with increased mortality (OR 1.14) [13].

The combination of anemia and LVH may be associated with an even higher risk of adverse cardiovascular outcomes [37]. Among 2423 CKD patients in four population-based studies, the presence of anemia and LVH was correlated with the risk of the primary composite outcome of myocardial infarction, stroke, and death [37]. LVH was associated with an increased risk for composite and cardiac outcomes (hazard ratio [HR] 1.67, 95% CI 1.34-2.07 and HR 1.62, 95% CI 1.18-2.24, respectively), while anemia was associated with increased risk for only the composite outcome (HR 1.51, 95% CI 1.27-1.81). The combination was associated with a higher increased risk for both study outcomes compared with individuals with neither risk factor (HR 4.15, 95% CI 2.62-6.56 and HR 3.92, 95% CI 2.05-7.48).

In another study of 415 CKD patients, the combination of anemia and LVH also increased the risk of a cardiovascular event (defined as cardiovascular death, hospitalization for unstable angina or HF, nonfatal myocardial infarction, ventricular arrhythmia, or transient ischemic attack/stroke) (HR 4.3, 95% CI 1.4-13) [38]. As noted above, however, treatment of anemia to normal or near-normal Hb levels with ESAs does not reduce morbidity or mortality among patients with CKD, including dialysis patients. (See 'Effect of anemia treatment on LVH' above.)

PROGRESSION OF CHRONIC KIDNEY DISEASE — 

Anemia may be a risk factor for progression of CKD, including to end-stage kidney disease (ESKD) [39,40]. As an example, one four-year study of over 1500 patients with diabetic nephropathy found that, compared with patients with the highest baseline hemoglobin (Hb) levels (>13.8 g/dL), patients with lower Hb levels had a nearly twofold increase in the adjusted risk of developing ESKD [41]. In another study of 415 CKD patients, the combination of anemia and left ventricular hypertrophy (LVH) was also associated with faster renal decline compared with patients with no anemia and no LVH (estimated glomerular filtration rate [eGFR] slope -2.66±0.23 versus -0.59±0.23 mL/min/1.73 m2 per year) and compared with patients with LVH but no anemia (eGFR slope -1.05±0.26 mL/min/1.73 m2 per year) [38]. Several other studies have similarly supported the relationship between anemia and more rapid CKD progression in various populations [42-44].

The mechanism for a faster decline in kidney function with more severe anemia is not known with certainty but might involve low-grade kidney ischemia or effects of underlying inflammation causing both anemia and CKD progression. From animal models of ischemic and nephrotoxic kidney injury, various mechanisms by which erythropoietin might have renoprotective effects have been proposed. These include reduced apoptosis, increased tubular regeneration, decreased caspase activity, and decreased interstitial fibrosis [45-48].

There is conflicting evidence concerning the effect of correction of anemia on the rate of progression of renal failure [49-55]. In the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), 4038 patients with type 2 diabetes and CKD (eGFR between 20 to 60 mL/min/1.73 m2) were randomly assigned to receive darbepoetin alfa to achieve a target Hb level of 13 g/dL or to placebo, with darbepoetin administered if the Hb level was <9 g/dL [56]. The mean achieved Hb level was 12.5 g/dL and 10.6 g/dL in the darbepoetin and placebo groups, respectively. At a median follow-up of 29 months, there was no difference between groups in the risk of ESKD (16.8 versus 16.3 percent in placebo, hazard ratio [HR] 1.02, 95% CI 0.87-1.18). (See "Treatment of anemia in patients on dialysis".)

A secondary analysis of the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial [53], however, found a greater risk of a CKD progression composite endpoint (doubling of the creatinine, initiation of kidney replacement therapy [KRT], or death) and a greater rate of KRT initiation in the higher Hb target group [57]. Authors of one meta-analysis noted that larger trials of anemia treatment in patients with CKD suggested a trend for increased risk of CKD progression with higher Hb targets; in the overall pooled analysis, however, no difference was detected between higher versus lower targets [58]. A meta-analysis that included 19 studies and 993 participants concluded that, for most measures of CKD progression, erythropoiesis-stimulating agent (ESA) treatment was not different than placebo or no treatment [59].

Two meta-analyses that included trials comparing higher versus lower hemoglobin targets, or ESA treatment versus control, concluded that there was no significant protective effect of higher targets or ESA treatment on CKD progression [60,61].

SUMMARY AND RECOMMENDATIONS

●Anemia and adverse cardiovascular outcomes – Among patients on dialysis, severe anemia is a risk factor for the development and progression of left ventricular hypertrophy (LVH), heart failure (HF), and mortality. (See 'Role of anemia' above and 'Role of anemia in patients with heart failure' above.)

●Effect of anemia treatment – The treatment of severe anemia with erythropoiesis-stimulating agents (ESAs) is associated with improvement of LVH and clinical manifestations of HF. However, increased morbidity and/or mortality have been associated with attaining normal or near-normal hemoglobin (Hb) levels with ESAs. (See 'Effect of anemia treatment on LVH' above and 'Effect of treatment of anemia on heart failure' above and 'Mortality' above.)

●Anemia and progression of chronic kidney disease (CKD) – Among patient with nondialysis CKD, anemia may be a risk factor for progression of kidney dysfunction to end-stage kidney disease (ESKD). The treatment of moderate anemia with ESAs has not been convincingly demonstrated to decrease progression to ESKD. (See 'Progression of chronic kidney disease' above.)

  1. United States Renal Data System. USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 2013.
  2. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351:1296.
  3. Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10:1606.
  4. McClellan WM, Flanders WD, Langston RD, et al. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002; 13:1928.
  5. Astor BC, Arnett DK, Brown A, Coresh J. Association of kidney function and hemoglobin with left ventricular morphology among African Americans: the Atherosclerosis Risk in Communities (ARIC) study. Am J Kidney Dis 2004; 43:836.
  6. Wittbrodt ET, James G, Kumar S, et al. Contemporary outcomes of anemia in US patients with chronic kidney disease. Clin Kidney J 2022; 15:244.
  7. Parfrey PS, Foley RN, Harnett JD, et al. Outcome and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant 1996; 11:1277.
  8. Paoletti E, Specchia C, Di Maio G, et al. The worsening of left ventricular hypertrophy is the strongest predictor of sudden cardiac death in haemodialysis patients: a 10 year survey. Nephrol Dial Transplant 2004; 19:1829.
  9. Stewart GA, Gansevoort RT, Mark PB, et al. Electrocardiographic abnormalities and uremic cardiomyopathy. Kidney Int 2005; 67:217.
  10. Middleton RJ, Parfrey PS, Foley RN. Left ventricular hypertrophy in the renal patient. J Am Soc Nephrol 2001; 12:1079.
  11. Park M, Hsu CY, Li Y, et al. Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 2012; 23:1725.
  12. Harnett JD, Kent GM, Foley RN, Parfrey PS. Cardiac function and hematocrit level. Am J Kidney Dis 1995; 25:S3.
  13. Foley RN, Parfrey PS, Harnett JD, et al. The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease. Am J Kidney Dis 1996; 28:53.
  14. Paoletti E, De Nicola L, Gabbai FB, et al. Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension. Clin J Am Soc Nephrol 2016; 11:271.
  15. Frank H, Heusser K, Höffken B, et al. Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients. Kidney Int 2004; 66:832.
  16. Silverberg DS, Wexler D, Blum M, et al. Erythropoietin should be part of congestive heart failure management. Kidney Int Suppl 2003; :S40.
  17. London GM. Left ventricular alterations and end-stage renal disease. Nephrol Dial Transplant 2002; 17 Suppl 1:29.
  18. Martinez-Vea A, Marcas L, Bardají A, et al. Role of oxidative stress in cardiovascular effects of anemia treatment with erythropoietin in predialysis patients with chronic kidney disease. Clin Nephrol 2012; 77:171.
  19. van der Meer P, Voors AA, Lipsic E, et al. Erythropoietin in cardiovascular diseases. Eur Heart J 2004; 25:285.
  20. Parfrey PS, Lauve M, Latremouille-Viau D, Lefebvre P. Erythropoietin therapy and left ventricular mass index in CKD and ESRD patients: a meta-analysis. Clin J Am Soc Nephrol 2009; 4:755.
  21. Akaishi M, Hiroe M, Hada Y, et al. Effect of anemia correction on left ventricular hypertrophy in patients with modestly high hemoglobin level and chronic kidney disease . J Cardiol 2013; 62:249.
  22. Eckardt KU, Scherhag A, Macdougall IC, et al. Left ventricular geometry predicts cardiovascular outcomes associated with anemia correction in CKD. J Am Soc Nephrol 2009; 20:2651.
  23. Tan W, Wang X, Sun Y, et al. Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial. J Intern Med 2024; 295:620.
  24. Kottgen A, Russell SD, Loehr LR, et al. Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol 2007; 18:1307.
  25. Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol 2001; 37:1775.
  26. Silverberg DS, Wexler D, Blum M, et al. Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases. Perit Dial Int 2001; 21 Suppl 3:S236.
  27. Silverberg DS, Wexler D, Blum M, et al. The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Nephrol Dial Transplant 2003; 18:141.
  28. Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 2000; 35:1737.
  29. Kotecha D, Ngo K, Walters JA, et al. Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials. Am Heart J 2011; 161:822.
  30. Kang J, Park J, Lee JM, et al. The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials. Int J Cardiol 2016; 218:12.
  31. Swedberg K, Young JB, Anand IS, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 2013; 368:1210.
  32. Ghali JK, Anand IS, Abraham WT, et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 2008; 117:526.
  33. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136:e137.
  34. Wish JB, Anker SD, Butler J, et al. Iron Deficiency in CKD Without Concomitant Anemia. Kidney Int Rep 2021; 6:2752.
  35. Walther CP, Triozzi JL, Deswal A. Iron deficiency and iron therapy in heart failure and chronic kidney disease. Curr Opin Nephrol Hypertens 2020; 29:508.
  36. Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis. N Engl J Med 2019; 380:447.
  37. Weiner DE, Tighiouart H, Vlagopoulos PT, et al. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 2005; 16:1803.
  38. Chang JM, Chen SC, Huang JC, et al. Anemia and left ventricular hypertrophy with renal function decline and cardiovascular events in chronic kidney disease. Am J Med Sci 2014; 347:183.
  39. Astor BC, Coresh J, Heiss G, et al. Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2006; 151:492.
  40. Levin A, Djurdjev O, Duncan J, et al. Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes. Nephrol Dial Transplant 2006; 21:370.
  41. Mohanram A, Zhang Z, Shahinfar S, et al. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int 2004; 66:1131.
  42. Hoshino J, Muenz D, Zee J, et al. Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD. J Ren Nutr 2020; 30:404.
  43. Yi SW, Moon SJ, Yi JJ. Low-normal hemoglobin levels and anemia are associated with increased risk of end-stage renal disease in general populations: A prospective cohort study. PLoS One 2019; 14:e0215920.
  44. Go AS, Yang J, Tan TC, et al. Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus. BMC Nephrol 2018; 19:146.
  45. Chatterjee PK. Pleiotropic renal actions of erythropoietin. Lancet 2005; 365:1890.
  46. Chung SD, Huang KH, Liao CH, et al. Acute heart failure with elevated cardiac enzymes. Kidney Int 2007; 72:521.
  47. Geng XC, Hu ZP, Lian GY. Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation. Mol Med Rep 2015; 11:3860.
  48. Bartnicki P, Kowalczyk M, Rysz J. The influence of the pleiotropic action of erythropoietin and its derivatives on nephroprotection. Med Sci Monit 2013; 19:599.
  49. Jungers P, Choukroun G, Oualim Z, et al. Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients. Nephrol Dial Transplant 2001; 16:307.
  50. Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int 2004; 66:753.
  51. Rossert J, Levin A, Roger SD, et al. Effect of early correction of anemia on the progression of CKD. Am J Kidney Dis 2006; 47:738.
  52. Drüeke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355:2071.
  53. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355:2085.
  54. Hayashi T, Uemura Y, Kumagai M, et al. Effect of achieved hemoglobin level on renal outcome in non-dialysis chronic kidney disease (CKD) patients receiving epoetin beta pegol: MIRcerA CLinical Evidence on Renal Survival in CKD patients with renal anemia (MIRACLE-CKD Study). Clin Exp Nephrol 2019; 23:349.
  55. Fliser D, Dellanna F, Koch M, et al. Early low-dose erythropoiesis-stimulating agent therapy and progression of moderate chronic kidney disease: a randomized, placebo-controlled trial. Nephrol Dial Transplant 2017; 32:279.
  56. Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361:2019.
  57. Inrig JK, Barnhart HX, Reddan D, et al. Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. Am J Kidney Dis 2012; 60:390.
  58. Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med 2010; 153:23.
  59. Cody JD, Hodson EM. Recombinant human erythropoietin versus placebo or no treatment for the anaemia of chronic kidney disease in people not requiring dialysis. Cochrane Database Syst Rev 2016; :CD003266.
  60. Covic A, Nistor I, Donciu MD, et al. Erythropoiesis-stimulating agents (ESA) for preventing the progression of chronic kidney disease: a meta-analysis of 19 studies. Am J Nephrol 2014; 40:263.
  61. Elliott S, Tomita D, Endre Z. Erythropoiesis stimulating agents and reno-protection: a meta-analysis. BMC Nephrol 2017; 18:14.
Topic 1925 Version 31.0

References

1 : United States Renal Data System. USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 2013.

2 : Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

3 : The clinical epidemiology of cardiac disease in chronic renal failure.

4 : Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study.

5 : Association of kidney function and hemoglobin with left ventricular morphology among African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

6 : Contemporary outcomes of anemia in US patients with chronic kidney disease.

7 : Outcome and risk factors for left ventricular disorders in chronic uraemia.

8 : The worsening of left ventricular hypertrophy is the strongest predictor of sudden cardiac death in haemodialysis patients: a 10 year survey.

9 : Electrocardiographic abnormalities and uremic cardiomyopathy.

10 : Left ventricular hypertrophy in the renal patient.

11 : Associations between kidney function and subclinical cardiac abnormalities in CKD.

12 : Cardiac function and hematocrit level.

13 : The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

14 : Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension.

15 : Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients.

16 : Erythropoietin should be part of congestive heart failure management.

17 : Left ventricular alterations and end-stage renal disease.

18 : Role of oxidative stress in cardiovascular effects of anemia treatment with erythropoietin in predialysis patients with chronic kidney disease.

19 : Erythropoietin in cardiovascular diseases.

20 : Erythropoietin therapy and left ventricular mass index in CKD and ESRD patients: a meta-analysis.

21 : Effect of anemia correction on left ventricular hypertrophy in patients with modestly high hemoglobin level and chronic kidney disease .

22 : Left ventricular geometry predicts cardiovascular outcomes associated with anemia correction in CKD.

23 : Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial.

24 : Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study.

25 : The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study.

26 : Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases.

27 : The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron.

28 : The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

29 : Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials.

30 : The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials.

31 : Treatment of anemia with darbepoetin alfa in systolic heart failure.

32 : Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.

33 : 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.

34 : Iron Deficiency in CKD Without Concomitant Anemia.

35 : Iron deficiency and iron therapy in heart failure and chronic kidney disease.

36 : Intravenous Iron in Patients Undergoing Maintenance Hemodialysis.

37 : Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease.

38 : Anemia and left ventricular hypertrophy with renal function decline and cardiovascular events in chronic kidney disease.

39 : Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study.

40 : Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes.

41 : Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy.

42 : Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

43 : Low-normal hemoglobin levels and anemia are associated with increased risk of end-stage renal disease in general populations: A prospective cohort study.

44 : Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus.

45 : Pleiotropic renal actions of erythropoietin.

46 : Acute heart failure with elevated cardiac enzymes.

47 : Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation.

48 : The influence of the pleiotropic action of erythropoietin and its derivatives on nephroprotection.

49 : Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients.

50 : Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial.

51 : Effect of early correction of anemia on the progression of CKD.

52 : Normalization of hemoglobin level in patients with chronic kidney disease and anemia.

53 : Correction of anemia with epoetin alfa in chronic kidney disease.

54 : Effect of achieved hemoglobin level on renal outcome in non-dialysis chronic kidney disease (CKD) patients receiving epoetin beta pegol: MIRcerA CLinical Evidence on Renal Survival in CKD patients with renal anemia (MIRACLE-CKD Study).

55 : Early low-dose erythropoiesis-stimulating agent therapy and progression of moderate chronic kidney disease: a randomized, placebo-controlled trial.

56 : A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.

57 : Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

58 : Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease.

59 : Recombinant human erythropoietin versus placebo or no treatment for the anaemia of chronic kidney disease in people not requiring dialysis.

60 : Erythropoiesis-stimulating agents (ESA) for preventing the progression of chronic kidney disease: a meta-analysis of 19 studies.

61 : Erythropoiesis stimulating agents and reno-protection: a meta-analysis.