Chronic Kidney Disease: Better Care = Better Outcomes
Chronic kidney disease (CKD) is a global health problem. In the United States, the incidence and prevalence is rising. CKD results in poor health outcomes, is often associated with and/or caused by comorbid conditions such as hypertension, diabetes mellitus, etc. Treatment of causes and comorbidities improves overall health for these patients and serves to slow the progression of disease.
Patients with moderate to severe CKD, along with those with overt renal failure, have a significant risk of developing anemia. Data from the National Kidney Foundation indicate that more than 40% of patients with Stage 3-4 CKD are anemic and the prevalence is roughly 75% in those with Stage 5 disease.¹ Anemia is a result of many factors, including decreased erythropoietin synthesis, occult or overt blood loss, poor red blood cell survivability, nutritional deficiencies of vitamin B12, folate, and very commonly both an absolute and functional iron deficiency.
As iron-deficiency anemia is common, early assessment of iron status is vitally important. Iron deficiency is likely present if transferrin saturation (TSAT) is less than 20% and serum ferritin is less than 200ng/mL. Even those with ferritin levels above 200ng/mL may suffer from functional iron deficiency i.e. dysfunctional absorption and distribution of iron stores.
Anemia is an independent risk factor for increased mortality in patients with CKD, with a risk of death equivalent to patients diagnosed with congestive heart failure and diabetes combined.² There is strong evidence that aggressive diagnosis and treatment of anemia, particularly iron-deficiency anemia, may slow progression of disease and improve overall outcomes for these patients.³
Historically, treatment modalities for iron-deficiency anemia have included erythropoietin stimulating agents (ESAs) either with or without iron supplementation. Four randomized controlled trials in both non-dialysis and dialysis-dependent CKD patients have cast some doubt on the safety of ESAs, particularly if hemoglobin (Hgb) targets of ≥ 13 g/dL and high ESA doses are utilized.⁵ ⁶ ⁷ The DRIVE Study, published in 2007, found the addition of I.V. iron resulted in a faster response and a greater magnitude of response while requiring a lower dose of ESA.⁸ A 2010 study in non-dialysis-dependent CKD patients showed an increase in TSAT and Hgb response with the use of I.V. iron alone.⁸
Current recommendations by the Kidney Disease: Improving Global Outcomes (KDIGO) group include early assessment for anemia, particularly iron deficiency anemia.⁹ Treatment options include ESAs with iron supplementation or an initial trial with I.V. iron alone. Maintenance of TSAT above 30% and serum ferritin levels above 200ng/mL are recommended. Hgb levels between 9.0-11.5 g/dL may be targeted, with caution not to exceed Hgb levels of 13g/dL due the increased risk of thromboembolic adverse events. TSAT above 50% and/or ferritin levels above 500ng/mL should be avoided in order to prevent iron overload. Treatment options must be customized for individual patients based on severity of illness, age, gender, comorbid conditions, etc. Cost of treatment, especially the use of ESAs should be evaluated in each case.
The use of red cell transfusion to treat chronic anemia in CKD patients is not recommended in the 2012 KDOQI guidance document. Acute anemia in hemorrhaging patients or significant symptomatic anemia in the unstable patient with an acute coronary syndrome may necessitate transfusion. The risks of transfusion, including but not limited to, acute transfusion reactions and pulmonary complications should be considered in the transfusion decision. For those patients eligible for kidney transplantation, transfusion should be avoided unless absolutely necessary to minimize the risk for alloimmunization.
In the end, the primary goal for the millions of patients diagnosed with CKD is to treat the underlying cause(s) and to slow progression of this potentially devastating illness. The current literature and clinical practice guidelines highlight the many options to intervene on behalf of patients with CKD and concomitant anemia. Early diagnosis, aggressive treatment and on-going continuous monitoring are necessary to achieve improved outcomes and quality of life.
- National Kidney Foundation Am J Kidney Dis 2006; 47 (suppl 3): S1-S45
- Astor B et al. Am Heart J 2006; 151: 492-500
- Gouva C et al. Kidney Int 2004; 66: 753-760
- Besarb A et al. N Engl J Med 1998; 339: 584-590
- Singh A et al. N Engl J Med 2006; 355: 2085-2098
- Dreucke T et al. N Engl J Med 2006; 355: 2071 -2084
- Pfeffer M et al. N Engl J Med 2009; 361: 2019-2032
- Coyne D et al. J Am Soc Nephrol 2007; 18: 975-984
- KDOQI. Kidney Int 2012; 2 (suppl): 283-287