The presence and severity of anemia in kidney disease increasesmarkedly with lower estimated glomerular filtration rates (eGFRs) and is associated with multiple adverse outcomes, a large cohort study has found.

“Anemia, defined by the World Health Organization as a hemoglobin concentration of < 13 g/dL in men and < 12 g/dL in women, is common among patients with chronic kidney disease (CKD),” Danielle Farrington, MD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues observe.

They also found that most people with anemia did not have their iron levels checked. Indeed “studies to detect iron deficiency are conducted in less than one in five patients with anemia regardless of eGFR level, suggesting a need for greater testing and potentially for iron supplementation,” the researchers note.

Although iron studies were checked infrequently, low iron test results were common in those tested.

“I think that when physicians see CKD patients with anemia, they often make the assumption that the cause is anemia of CKD, and thus, they do not check iron levels,” Farrington noted in an email to Medscape Medical News.

“This highlights the need for increased testing of iron studies in patients with anemia, as iron supplementation is an effective and low-risk intervention,” Farrington and colleagues say in their study published in the American Journal of Kidney Disease.

Severe Anemia Increases as eGFR Drops

The analysis included 5,004,957 individuals across 57 healthcare centers in the US registered in a database between 2016 and 2019. The primary outcomes included end-stage kidney disease (ESKD), cardiovascular disease (CVD), coronary heart disease (CHD), stroke, heart failure, and death.

Low iron test results were defined as a serum ferritin ≤ 100 ng/mL or a serum transferrin saturation ≤ 20% or both.

“The mean hemoglobin was 14 g/dL and the mean eGFR was 87 mL/min/1.73m2,” the authors note. Severe anemia was defined as hemoglobin < 10 g/dL.

The prevalence of severe anemia increased as eGFR dropped in both men and women (Table 1).

Table 1. Anemia prevalence by eGFR in men and women

eGFR mL/min/1.73m2 (men) Anemia prevalence
60-70 1.3%
45-59 3.1%
30-44 7.5%
15-29 17.4%
< 15 29.7%
eGFR mL/min/1.73m2 (women) Anemia prevalence
60-70 1.9%
45-59 3.9%
30-44 8.6%
15-29 19.4%
< 15 37.6%

Iron Levels Checked Infrequently

In patients with anemia, iron, as well as vitamin B12, levels were infrequently checked.

“Of all men with anemia, only 15.6% and 11.7% had iron studies and vitamin B12 levels available, respectively,” the investigators report. Among women with anemia, 19.6% had iron studies available and 13.9% had vitamin B12 levels available.

“In both men and women with anemia, the prevalence of low iron test results decreased with lower eGFR.” Farrington and colleagues report, although low iron test results were more common in women than men, Farrington noted.

She also thinks that physicians are less likely to check iron studies when the degree of anemia is mild. 

And somewhat paradoxically, more men and women with higher eGFR levels had low iron test results. For example, in those with anemia and an eGFR of ≥ 90 mL/min/1.73m2, almost 65% of men and over 90% of women had low iron test results.

In contrast, in those with anemia and an eGFR < 15 mL/min/1.73m2, only about 40% of men and slightly over 50% of women had low iron test results.

As Farrington explained, iron deficiency anemia portends a better outcome than other common causes of anemia, which are often associated with many other comorbidities.

“Those with anemia who are not iron deficient are more likely to have anemia of CKD or anemia of a chronic disease as the cause for their anemia, [both of] which are associated with worse outcomes due to the comorbidities that go along with them,” she emphasized. 

“Ferritin and iron studies should be checked in all patients with anemia regardless of whether they have CKD or not, and iron deficiency anemia should be treated and evaluated appropriately,” she emphasized. 

Vitamin B12 deficiency was rare across all categories of eGFR, with a total prevalence of 3.0% in men with anemia and 3.5% of women with anemia, the authors observe.

Use of erythropoiesis-stimulating agents (ESAs) to target a normal hemoglobin level was low, at < 4%, probably because their use has been associated with increased cardiovascular risk, the researchers note. 

Rate of Comorbidities, Death Three Times Higher With Severe Anemia

Importantly, there was an increased risk of ESKD, CVD, CHD, stroke, heart failure, and death after adjusting for age, race, eGFR, and the presence of comorbidities in patients with lower hemoglobin levels.

For example, the adjusted hazard ratio for death was almost three times as high in men with a hemoglobin < 9 g/dL compared to men with a hemoglobin between 12 to 13 g/dL.

The project was supported by the National Kidney Foundation.

Farrington has reported no relevant financial relationships.

Am J Kidney Dis. Published online September 23, 2022. Abstract

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