Renal Anaemia

Implications of CKD-Related Anaemia

CKD-related anaemia is a major public health concern. It is associated with an increased risk of morbidity, mortality and hospitalisation, diminished physical well-being and reduced patient quality of life.^2,6-8

Impact on the cardiovascular system: Anaemia has a negative impact on nearly every major system and organ of the body, but the most serious effects are related to the cardiovascular system. CVD is highly prevalent in all stages of CKD and is the leading cause of morbidity and mortality in dialysis patients.^1,3,9 In patients with early-stage CKD, anaemia contributes to the development of left ventricular hypertrophy, an independent risk factor for mortality.² Anaemia can also increase the risk of stroke and congestive heart failure (CHF). The addition of anaemia to diagnoses of CKD, CHF, or both CKD and CHF (the cardio-renal-anaemia syndrome) (Figure 3)¹⁰ has been found to increase the risk of death or development of stage 5 CKD by factors of 1.2 to 2.2.¹¹

Impact on quality of life: A cross-sectional analysis of the Renal Research Institute-CKD study found that quality of life was significantly impaired in patients with CKD.⁸ Furthermore, the presence of anaemia was associated with decreased quality of life scores in most domains of the standard validated Medical Outcomes Study Short Form-36 for patients with CKD, including physical function, physical role, pain, general health, mental health, emotional role, social function, vitality, physical component scale, and mental component scale.⁸ Post-hoc quality of life analyses using the Linear Analogue Scale Assessment and the Kidney Disease Questionnaire subscales demonstrated that maximal gain in quality of life was obtained when Hb levels were maintained within an 11–12 g/dL range.¹³

Many published reports have highlighted the negative health consequences of anaemia in patients with CKD:

A 60% increase in risk of left ventricular hypertrophy with each 1 g/dL decrease in Hb level was found in a study of early kidney disease.⁶
A negative impact on cardiac structure, cardiac morbidity, and mortality in patients with anaemia was reported in a study that followed 432 patients with stage 5 CKD over an average of 41 months.²
Regression analyses have demonstrated an independent association between a 1 g/dL decline in mean Hb and several critical outcomes: left ventricular dilation on repeat echocardiograms (42%), de novo cardiac failure (28%), recurrent cardiac failure (20%), and death while on dialysis (14%).
A relative risk of death of 2.11 was reported in patients with Hb <9 g/dL compared with patients whose Hb was 11 to <12 g/dL. A higher average number of hospitalisations was also observed in the patients with Hb <9 g/dL compared with those with Hb ≥13 g/dL (2.45 and 1.65 respectively).⁷
A growing body of evidence shows that early detection and treatment of CKD-related anaemia may prevent or delay some of the adverse outcomes of CKD, including complications from decreased kidney function and development of CVD.^4,5,12

Adapted from Silverberg et al 2003.¹⁰

The cardio-renal-anaemia syndrome is a triangular relationship between CHF, CKD, and anaemia.¹⁰ CKD can cause or worsen anaemia and CHF, which can also cause or worsen CKD and each other. This syndrome has a complex pathophysiology. In patients with anaemia, hypoxia leads to peripheral vasodilation, decreased vascular resistance, and reduced blood pressure. To maintain blood pressure, sympathetic activity triggers elevations in peripheral vasoconstriction, heart rate, and stroke volume. However, these increases also lead to renal vasoconstriction, resulting in reduced blood flow to the kidney, reduction in GFR, and renal ischaemia. This process can be aggravated by the renin-angiotensin-aldosterone system. The resulting fluid retention¹⁴ and increased plasma volume cause left ventricular hypertrophy, which leads to necrosis and apoptosis of myocardial cells. The outcome is CHF.

Levels of tumour necrosis factor alfa are increased in CHF. Increased production of such cytokines has been implicated in the development of CKD-related anaemia¹⁰ and may also worsen anaemia in patients with CKD and CHF, creating a feed-forward system of disease progression.

It is critical that physicians treating CKD patients understand the relationship between CKD, CHF, and anaemia, because untreated anaemia will become more severe and may lead to progression of CKD and development or progression of CHF.

References:
1. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2006.
2. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease. Am J Kidney Dis. 1996;28:53–61.
3. Locatelli F, Pozzoni P, Tentori F, del Vecchio L. Epidemiology of cardiovascular risk in patients with chronic kidney disease. Nephrol Dial Transplant. 2003;18(Suppl 7):vii2-vii9.
4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(Suppl 1):S1-S266.
5. Johnson CA, Levey AS, Coresh J, Levin A, Lau J, Eknoyan G. Clinical practice guidelines for chronic kidney disease in adults: Part I. Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70:869–876.
6. Levin A, Thompson CR, Ethier J, Carlisle EJ, Tobe S, Mendelssohn D, Burgess E, Jindal K, Barrett B, Singer J, Djurdjev O. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis. 1999;34:125–134.
7. Ofsthun N, Labrecque J, Lacson E, Keen M, Lazarus JM. The effects of higher hemoglobin levels on mortality and hospitalization in hemodialysis patients. Kidney Int. 2003;63:1908–1914.
8. Perlman RL, Finkelstein FO, Liu L, Roys E, Kiser M, Eisele G, Burrows-Hudson S, Messana JM, Levin N, Rajagopalan S, Port FK, Wolfe RA, Saran R. Quality of life in chronic kidney disease (CKD): a cross-sectional analysis in the Renal Research Institute-CKD study. Am J Kidney Dis. 2005;45:658–666.
9. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(Suppl 3):S112–S119.
10. Silverberg DS, Wexler D, Blum M, Schwartz D, Wollman Y, Iaina A. Erythropoietin should be part of congestive heart failure management. Kidney Int Suppl. 2003;(87):S40–S47.
11. Gilbertson DT, Li S, Murray A, Herzog C, Collins A. The competing risks of death vs. ESRD in Medicare beneficiaries 65+ with chronic kidney disease, CHF, and anemia. J Am Soc Nephrol. 2002;13:439A (abstract SA-P0848).
12. Remuzzi G, Ruggenenti P, Perico N. Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition. Ann Intern Med. 2002;136:604–615.
13. Lefebvre P, Vekeman F, Sarokhan B, Enny C, Provenzano R, Cremieux PY. Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa. Curr Med Res Opin. 2006;22:1929–1937.
14. Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA, Harris PC. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J. 1993;70:357–362.