Anemia in CKD Associated With Lower eGFR, Adverse Outcomes

A study published in the American Journal of Kidney Diseases found that patients with chronic kidney disease (CKD) who had severe anemia were more likely to have lower glomerular filtration rate (eGFR) and multiple adverse outcomes.

Anemia, which is common in patients with CKD, is defined as a hemoglobin concentration of less than 13 g/dL in men and less than 12 g/dL in women. It has been found in previous studies that people with anemia have an increased risk of adverse cardiovascular outcomes and death. This current study aimed to characterize the burden, risk factors, and risks associated with anemia.

The data for this study were from the Optum Labs Data Warehouse. The data included deidentified claims and electronic health record data from across the United States. Patients with an outpatient complete blood count and serum creatinine measured within 30 days of each other were included in the study. All complete blood count draws were from the 2016 calendar year.

Follow-up data were collected until December 31, 2019. Hemoglobin levels less than 13 g/dL in men and less than 12 g/dL in women were defined as anemia, with hemoglobin of less than 10 g/dL defined as severe anemia. Adverse outcomes that were evaluated included end-stage kidney disease (ESKD), cardiovascular disease, coronary heart disease, stroke, heart failure, and death.

The analysis included 5,004,957 patients from 57 health care organizations. The population was made up of 42% male participants, the mean age was 54 years, and 10.1% identified as Black. The mean hemoglobin was 14 g/dL and the mean eGFR was 87 mL/min/1.73 m². A total of 35.6% of participants had a urine dipstick test, and 19% had at least a trace of proteinuria, with relatively similar proportions in both men and women. A total of 14.9% of participants had diabetes and 39.8% had hypertension.

Severe anemia was present in 1.3%, 3.1%, 7.5%, 17.4%, and 29.7% of men across the eGFR categories of 60 to 74, 45 to 59, 30 to 44, 15 to 29, and less than 15 mL/min/1.73 m², respectively. The prevalence of severe anemia in women was 1.9%, 3.9%, 8.6%, 19.4%, and 37.6%, respectively. This demonstrated an association between lower eGFR and the prevalence of anemia. Anemia was more prevalent in women compared with men across all eGFR categories. These associations remained after adjustment for age, race, and health care organization. Older age and Black race were associated with a higher prevalence of anemia.

A total of 15.6% and 11.7% of men had iron studies done and vitamin B12 levels available, respectively, whereas only 19.6% and 13.9% of women had each. Low iron test results were found in 60.4% of men and 81.3% of women with anemia. Prevalence of low iron decreased with a lower eGFR. Vitamin B12 deficiency was rare, with only 3.0% of men and 3.5% of women with anemia having low vitamin B12.

Lower hemoglobin was associated with an increased risk of ESKD, cardiovascular disease, coronary heart disease, stroke, heart failure, and death when adjusting for age, race, eGFR, prevalent cardiovascular disease, hypertension, urine albumin-creatinine ratio, diabetes, smoking, and health care organization. The adjusted HR for death was 2.91 (95% CI, 2.82-3.00) in men with a hemoglobin of less than 9 g/dL compared with men with a hemoglobin of 12 to 13 g/dL.

Interestingly, the authors noted, low iron test results in patients with anemia tended to be associated with a decreased risk of adverse outcomes compared with those without a low iron test result. The adjusted HR for ESKD was 0.76 (95% CI, 0.69-0.83) in patients with low iron test results compared with those without low iron test results. Low iron test results were also associated with a decreased risk of cardiovascular disease, coronary heart disease, stroke, heart failure, and death in women, whereas men only saw a decreased risk in ESKD, stroke, and death if they had lower iron test results.

There were some limitations to this study. The researchers relied on the International Classification of Diseases codes for a medical diagnosis making it possible to get inaccurate outcome measures. Death information is incomplete in the Optum Labs Data Warehouse. Care at centers not within the data set may have been missed. Residual confounding could not be ruled out due to the observational nature of the study.

The researchers concluded that the study “provides generalizable, precise estimates from a large clinical population on the full spectrum of anemia severity.” They highlighted the finding that low eGFR was associated with severe anemia in both men and women.

Reference

Farrington DK, Sang Y, Grams ME, et al. Anemia prevalence, type, and associated risks in a cohort of 5.0 million insured patients in the United States by level of kidney function. Am J Kidney Dis. Published online September 28, 2022. doi:10.1053/j.ajkd.2022.07.014