Patients with chronic kidney disease (CKD) who have both anemia and volume overload are at increased risk for adverse cardiovascular and renal outcomes, a new study suggests.

Researchers in Taiwan led by Der-Cherng Tarng, MD, PhD, of Taipei Veterans General Hospital, evaluated the influence of fluid status on hemoglobin levels and cardiovascular and renal outcomes in a prospective cohort of 326 patients with stage 3–5 CKD. A total of 221 patients (68%) had anemia. The investigators divided these patients according to the presence of volume overload (anemia with excess overhydration) or not (true anemia). The 2 groups were similar with respect to age, sex, smoking history, estimated glomerular filtration rate (eGFR), and ferritin levels. Diabetes and cardiovascular disease, however, were more common in the volume overload group.

The primary outcome—morbidity and mortality from cardiovascular causes—was a composite of myocardial infarction, hospitalization for congestive heart failure or unstable angina, or death from cardiovascular causes. The secondary outcome was renal events, either the first occurrence of a decline in eGFR of 50% or greater or development of end-stage renal disease requiring chronic dialysis.

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Results showed that fluid status was negatively correlated with hemoglobin levels at baseline. In multivariate analysis, overhydration was an independent predictor of low hemoglobin concentrations, the researchers reported online in the Journal of the American Heart Association.

During a median follow-up of 2.2 years, the primary outcome occurred in 3 (2.9%) patients who had no anemia, 5 (6.1%) who had true anemia, and 37 (26.6%) who had anemia with excess overhydration. In adjusted analyses, patients with true anemia (reduced red blood cell volume) and those with no anemia had a 69% and 76% decreased risk of cardiovascular events, respectively, compared with patients who had anemia and excess overhydration.

In addition, 9 patients in the no-anemia group (8.6%), 17 in the true-anemia group (20.7%), and 70 in the anemia with excess overhydration group (50.4%) experienced the secondary outcome.

With respect to renal events, 9 (8.6%) occurred in the no-anemia group, 17 (20.7%) occurred in the true-anemia group, and 70 (50.4%) occurred in the group with anemia and excess overhydration. Compared with patients who had anemia and excess overhydration, those with true anemia and no anemia had a 54% and 74% decreased risk of renal events, respectively.

In adjusted analyses, the researchers found no difference in cardiovascular and renal risks between the true-anemia and no-anemia groups.

Dr. Tarng’s group stated that their data demonstrate that fluid status, defined as the overhydration level, is among the major determinants of low hemoglobin concentrations in patients with stage 3–5 CKD. “Anemia in these patients was not only independently related to their impaired renal function, but also to an increased fluid status.”