Anemia Prevalence and Treatment Patterns in Patients with NDD-CKD

Patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD) commonly experience anemia; as CKD worsens, the prevalence of anemia increases in that patient population. Data of the prevalence of anemia in patients with NDD-CKD are from the 2007-20210 National Health and Nutrition Examination Survey (NHANES). NHANES data are representative of the population in the United States. However, the sample size is small and does not allow for subgroup analysis, creating a need for more recent data on the prevalence of anemia in NDD-CKD patients in order to assess trends of key factors such as age, sex, and race.

There are data available on treatment for anemia in patients with CKD stage 5 on dialysis, but few data on anemia treatment in patients with NDD-CKD stages 3 to 5. Anemia has been shown to be associated with increased hospitalizations and/or hospital days in patients with NDD-CKD, but information on ways anemia affects other healthcare utilization, such as emergency department or clinic visits or specialty care is lacking.

Wendy L. St. Peter, MD, and colleagues recently conducted a retrospective observational database study supported by a research contract from AstraZeneca, Inc. The study was designed to (1) update estimates of anemia prevalence in NDD-CKD patients with either Medicare or commercial insurance; (2) assess the prevalence of anemia in NDD-CKD patients by CKD stage, age, sex, and race; (3) examine treatment patterns in that patient population in the contemporary period following TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) results and the subsequent 2012 updates to the Kidney Disease Improving Global Outcomes practice guidelines for treating anemia in CKD and the enhanced FDA boxed warning in June 2011; and (4) define the healthcare burden/utilization in NDD-CKD patients with and without anemia. Study results were reported online in BMC Nephrology [doi.org/10.1186/s12882-018-0861-1].

The researchers utilized the 20% Medicare random sample for data on patients aged 66 to 85 years and the Truven Health MarketScan Commercial Claims and Encounters Database for information on commercially insured patients 18 to 63 years of age. NDD-CKD patients with and without anemia were selected from the two databases for the study period 2011-2013.

Inclusion criteria for the Medicare cohort were (1) at least 66 years of age as of the end date of a 1-year baseline period; (2) Medicare Parts A and B coverage; (3) not in a health maintenance organization; (4) not on dialysis during the baseline period or on day one of the follow-up period; and (5) alive on the first day of the follow-up period. Inclusion criteria for patients in the commercially insured cohort were (1) 18 to 63 years of age as of the end date of a 1-year baseline period; (2) commercial insurance coverage; (3) not on dialysis during the baseline period; and (4) enrollment in the commercial claim dataset for at least 1 day during a follow-up period. End-stage renal disease was an exclusion criterion in both data sources.

The 20% Medicare sample yielded 218,079 patients 66 to 85 years of age with stage 3-5 NDD-CKD; the Truven Health MarketScan Commercial Claims and Encounters Database yielded 56,188 stage 3-5 NDD-CKD patients 18 to 63 years of age during the study period.

Among the commercially insured patients, the overall prevalence of anemia was 28.0%; the prevalence increased with progression of CKD (stage 3, 22.4%; stage 4, 41.3%; stage 5, 53.9%). Among the older patients (Medicare), the overall anemia prevalence was 50.1% (stage 3, 43.9%; stage 4, 64.0%; stage 5, 72.8%). In both data sets, the prevalence increased with age and was higher in women and much higher in patients with comorbid conditions, with the exception of diabetes and hypertension. In the Medicare cohort, the prevalence was also higher in black patients.

The prevalence of comorbid and inflammatory conditions was generally higher in patients with anemia than in patients without anemia in both datasets. In the younger patients (commercial insurance) with and without anemia, the prevalence of arteriosclerotic heart disease was 23.6% versus 13.9%, congestive heart failure 21.4% versus 9.0%, dysrhythmia 19.5% versus 9.5%, and glomerulonephritis 7.8% versus 3.8%. In the older cohort (Medicare) with and without anemia, corresponding proportions were 52.2% versus 36.4%, 40.5% versus 20.1%, 43.8% versus 28.0%, and 6.0% versus 2.7%, respectively. There were increases in prevalence of comorbid conditions with progression of CKD.

Of the patients in the younger cohort with anemia (n=15,716), 26.2% received at least one type of treatment: 11.7% were treated with red blood cell (RBC) transfusion, 10.8% with erythropoietin-stimulating agents (ESAs), and 9.4% with IV iron. Among the patients receiving treatment for anemia, median times from anemia diagnosis to treatments were 21 days for ESAs, 33 days for RBC transfusion, and 44 days for IV iron. In the treated subgroup overall, 20% received two or more treatments (eg, RBC transfusion and ESA).

Among the Medicare cohort, treatment patterns were similar, with larger proportions receiving treatment. Of the patients with anemia (n=109,251), 34.0% received treatment for anemia: 22.2% with RCB transfusion, 12.7% with ESAs, and 6.7% with IV iron. Median times from anemia diagnosis to treatment were 18 days for ESAs, 34 days for RBC transfusion, and 84 days for IV iron.

Analyses of healthcare resource utilization found that, in general, there was an association between anemia and increased use of healthcare resources. Following adjustment for patient case-mix, hospital admissions for older patients with anemia were 1.33 times higher than for older patients without anemia (95% confidence interval [CI], 1.31-1.34); hematologist visits were 4.29 times higher (95% CI, 4.08-4.52) for older patients with anemia than for older patients without anemia. Among the younger cohort, hospital admissions were 1.42 times higher for those with anemia than for those without anemia (95% CI, 1.38-1.47), and hematologist visits were 2.90 times higher (95% CI, 2.76-3.04).

The researchers cited several limitations to the study, including the retrospective design, making regression relationships associations and not causal; the possibility of residual confounding; the possibility that not all of the anemia diagnoses were CKD-related; and the lack of information on fluid status, creating the possibility of confounding the relationship between CKD anemia and outcomes.

In summary, the researchers said, “Our study is the largest to date examining anemia prevalence in stage 3-5 NDD-CKD older Medicare-covered and younger commercially insured patients, allowing analysis by important subgroups such as age, race (Medicare only), and CKD stage. In a 2012 patient cohort, both younger and older patients with stage 3-5 NDD-CKD and diagnosed anemia were more likely to be treated with an RBC transfusion than with ESAs or IV iron. This is concerning due to the potential for increased panel-reactive antibodies and increased waiting time for kidney transplant. Although we showed increased healthcare utilization for NDD-CKD patients with anemia versus those without, further research is needed to determine whether future therapies such as HIF [hypoxia inducible factor] prolyl hydroxylase inhibitors, anemia treatment to lower hemoglobin targets with ESAs and iron, or treatment of specific subgroups (e.g., CKD with heart failure) can improve health outcomes and reduce healthcare utilization.”

Takeaway Points

  1. Researchers conducted a retrospective observational database study to update anemia prevalence estimates in two cohorts of patients with non-dialysis dependent chronic kidney disease (NDD-CKD) stage 3-5: patients 66-85 years of age (Medicare) and patients 18-63 years of age (commercial insurance).
  2. Overall prevalence of anemia among younger patients with NDD-CKD was 28.0%; for the older cohort, the prevalence was 50.1%.
  3. In general, anemia was associated with increased use of healthcare resources; hospital admissions for younger patients were 1.33 times higher for those with anemia compared with those without, and for older patients, 1.42 times higher.