Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease

Abstract

Background Anemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD. Methods Nondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate <60 mL/min/1.73 m2 were included. Logistic regression, multivariate Cox proportional hazards and Poisson regression models adjusted for demographics and comorbidities were used to assess the prevalence and correlates of absolute [transferrin saturation (TSAT) ≤20%, ferritin <100 ng/mL] and functional (TSA T≤20%, ferritin >100–500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization. Results Of 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12–1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05–1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07–1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1–1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07–1.21)]. Ferritin >500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26–1.51)]. Conclusions In a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference

“…In NDCKD patients, the US Veteran study, REport of COmorbidities in non-Dialysis Renal Disease Population in Italy (RECORD-IT), and Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDoppS) report that 21%-62% of patients have anemia, defined as Hb <12 g/dl or <12 g/dl in females and <13.5 g/dl in males, with increasing prevalence in more advanced CKD. [47][48][49] Moreover, 15%-72.8% have either ferritin <100 mg/l or TSAT <20%, and 8%-20% have both parameters below the threshold. 3,47,48,50,51 For HDCKD patients, data from United States Renal Data System 52 show that 64.5%, 14.4%, and 6.6% have Hb levels between 10-12 g/ dl, 9 and 10 g/dl, or below 9 g/dl, respectively.…”

“…58 Moreover, TSAT <20% is also associated with cardiovascular hospitalizations and mortality. 49,54,59 However, given the association of anemia and iron deficiency with other comorbidities, the truly independent risk of abnormal Hb and/or iron levels remains uncertain.…”

Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin

“…This cardiomyopathy may present as ischemic heart disease or heart failure, even when arterial vascular disease is absent [ 10 ]. Anemia has been associated with an increased risk of cardiovascular events and all-cause mortality in a number of observational studies [ 11 – 18 ], and the American Heart Association considers anemia to be a nontraditional (non-Framingham) cardiovascular risk factor in patients with CKD [ 10 ]. In a US study of > 900,000 patients with NDD-CKD, functional iron deficiency anemia was associated with an increased risk of mortality [hazard ratio (HR) 1.11, 95% CI 1.07–1.14] and an increased relative risk (RR) of cardiovascular hospitalization after 1 year (RR 1.21, 95% CI 1.12–1.30) and 2 years (RR 1.13, 95% CI 1.07–1.21) [ 11 ].…”

“…Anemia has been associated with an increased risk of cardiovascular events and all-cause mortality in a number of observational studies [ 11 – 18 ], and the American Heart Association considers anemia to be a nontraditional (non-Framingham) cardiovascular risk factor in patients with CKD [ 10 ]. In a US study of > 900,000 patients with NDD-CKD, functional iron deficiency anemia was associated with an increased risk of mortality [hazard ratio (HR) 1.11, 95% CI 1.07–1.14] and an increased relative risk (RR) of cardiovascular hospitalization after 1 year (RR 1.21, 95% CI 1.12–1.30) and 2 years (RR 1.13, 95% CI 1.07–1.21) [ 11 ]. Similarly, a Danish study of patients with dialysis-dependent-CKD (DD-CKD) and NDD-CKD found that anemia was associated with increased risks of major adverse cardiovascular events (MACE), acute hospitalization, and all-cause death [ 12 ], and a Japanese study of NDD-CKD patients reported that isolated anemia and iron deficiency anemia were associated with increased risks of cardiovascular-related and all-cause mortality [ 13 ].…”

Understanding Patient Perspectives and Awareness of the Impact and Treatment of Anemia with Chronic Kidney Disease: A Patient Survey in China

“… 8 There are well-established serious consequences associated with anemia in CKD, including CKD progression, cardiovascular disease, and increased mortality risk. 6 , 9–11 The presence of anemia with CKD is also associated with reduced health-related quality of life (HRQoL). 12 …”