Prevalence of anemia
Overall, the study population consisted of 1,903 patients aged 82.7 (7.8) years, with 51.9% men and a mean 7.3 (3.2) medications (Table 1).
Anemia had an overall prevalence of 66.7% of the study population and was slightly more common in Nephrology Units compared to Geriatric Units (75.6% vs 63.3%, p < 0.001). Patients with anemia were older and more commonly men; furthermore, they had a higher prevalence of low iron tests, hypoalbuminemia and higher neutrophil-to-lymphocyte (NLR) values compared to those without anemia; they also had atrial fibrillation, type 2 diabetes, COPD, and cancer, as well as a lower mean eGFR value; finally, anemic patients took more medications, with higher prevalence of both antianemic and potentially anemizing ones. Characteristics of anemic patients stratified by admission unit are reported in Supplementary Table 1. In summary, geriatric patients with anemia were older, with a higher prevalence of COPD, cardiovascular and cerebrovascular diseases, and a lower prevalence of type 2 diabetes mellitus compared to nephrology ones (p < 0.001). Moreover, patients admitted to Nephrology Units had a higher number of medications, a higher prescription of iron, vitamin B12, and folic acid. Prescription patterns slightly differed across admission units, partly in line with the median lower eGFR values in anemic patients discharged from nephrology units. Indeed, vitamin K antagonists and antiplatelet medications were more commonly prescribed in nephrology patients with anemia, while vitamin K antagonists had a higher prescription rate in geriatric units (Supplementary Table 1).
Characteristics of type and severity of anemia across admission units and CKD stages
Differences in severity and type of anemia in the overall study population and in the two settings are displayed in Fig. 1.
Pie charts showing prevalence of anemia severities and types in the overall study population and across geriatrics and nephrology admission units.
Almost two thirds of anemic patients were characterized by a mild reduction of hemoglobin concentration with no significant differences across admission units; moderate anemia was slightly above 30% in all units, while severe anemia had a relatively low prevalence; among types of anemia, normocytic normochromic and mixed forms were the most common ones, followed by macrocytic and microcytic hypochromic forms. No significant differences emerged among patients admitted to Geriatric and Nephrology units.
Stratification by CKD stages showed that prevalence of anemia increases with declining eGFR in the overall study population, ranging from 53.4% to 57.0% to 71.5% to 83.9% to 83.5% for patients with eGFR ≥ 60, 45–59.9, 30–44.9, and < 30, respectively (p < 0.001). The distribution of severity and type of anemia across eGFR categories and admission units is represented in Fig. 2.
Relative prevalence of anemia severities and types across eGFR categories in the overall study population and in the two admission units.
Decline of eGFR was associated with a graded increase in prevalence of moderate-severe anemia in overall study population and in both settings; more specifically, the most significant increase in the rate of moderate-severe anemia was observed for eGFR below 45 ml/min/1.73 m2 in both settings; no significant changes of types of anemia across eGFR stages were observed.
Diagnostic inertia in all anemic patients and in those with indication to ESA treatment
Assessment of iron status, vitamin B12 and folic acid levels was performed infrequently in patients with anemia (Table 2).
Of all patients with anemia, only 30.6%, 23.4%, and 22.1% had iron studies, vitamin B12 and folic acid levels available, respectively. Patients admitted to Nephrology Units presented significantly higher rates of iron study availability (37.8 vs 27.8% %, p < 0.001) and lower rates of vitamin B12 (16.3% vs 26.7%, p < 0.001), and folic acid assessment (15.6% vs 25.2%, p < 0.001). In general, among patients with anemia who underwent iron level assessment, more than a half resulted to have low iron tests, with higher prevalence in Nephrology Units compared to Geriatric Units (60.5% vs 55.3%, p < 0.001), and an increasing trend in patients with eGFR < 30 ml/min/1.73 m2; conversely, deficiencies of folic acid and vitamin B12 were less common.
Diagnostic inertia was also explored in patients with renal and hemoglobin criteria for ESA use (Table 3).
Overall, more than a half of patients satisfying these criteria were not routinely screened for iron status. Logistic regression analyses showing factors associated with lack of iron status assessment in bivariate and multivariate models are reported in Supplementary Table 2. Factors associated with diagnostic inertia related to iron status were different across admission units (Supplementary Table 3); in this regard, among geriatric patients, CHF and prescription of DOACs resulted to be positively associated with diagnostic inertia, while number of drugs was negatively associated with the outcome; as expected, iron treatment was negatively associated with the outcome in overall study population and nephrology patients.
Replacement inertia
Replacement inertia was relatively common in the study population. Indeed, iron replacement inertia was frequently encountered among anemic patients with low iron levels, reaching the prevalence of 81.4% of the overall study population, 84.2% and 77.0% of patients hospitalized in geriatric and nephrology units, respectively (p = 0.244). Among anemic patients with low serum folate, folate replacement inertia was found in 87.5% of all patients, ranging from 90.9% and 77.8% of geriatric and nephrology units respectively (p = 0.151). Finally, a half of the 12 patients with anemia and low vitamin B12 status were not treated with vitamin B12 supplements.
No factor was found to be associated with iron or replacement inertia in the overall study population (Supplementary Table 4).
ESA inertia
Prevalence and risk factors for therapeutic ESA inertia among patients with ESA indication are reported in Supplementary Table 5. ESA inertia was quite common in the study population (n = 219/326, 67.2%) with significantly higher rates in geriatric patients (173/203, 85.2% vs 46/123, 37.4%, p < 0.001). In most cases, patients with ESA inertia were not routinely screened for iron tests (71.5%), especially in Geriatric units (75.4 vs 65.0%); in this subgroup of patients with ESA inertia and missed iron assessment, only a few were treated with intravenous/oral iron supplementation (10.8% in all units, 11.4% in geriatric units, 7.7% in nephrology units). Analyses of factors associated with ESA inertia in logistic regression bivariate and multivariate models are reported in Table 4.
In the overall study population, COPD and increasing eGFR were associated with increased risk of ESA inertia in fully-adjusted models, while male sex, vitamin B12/folate treatment, and admission to Nephrology Units were negatively associated with the outcome in the study population. Stratified analyses by admission unit showed that eGFR and cancer were positively associated with ESA inertia among geriatric patients, while eGFR only was positively associated with the outcome in nephrology units.
To capture the complex non-linear relationship between eGFR, and ESA inertia, we fitted restricted cubic splines in the whole population, geriatric and nephrology units (Fig. 3).
Restricted cubic spline showing the association between eGFR (as measured through BIS equation) and the odds ratio of ESA inertia in patients with ESA indication (Hb < 10 g/dl, eGFR < 60 ml/min, and either normal-high iron status or low iron status with concomitant iron treatment), in the overall study population and in geriatrics and nephrology units separately. Odds ratios with 95% confidence intervals represent the risk of association compared to the median value of the eGFR distribution in the three study populations.
Overall, a trend of increased ESA inertia was present for less advanced CKD stages with specific cut-off of increased risk at eGFR > 37 ml/min/1.73 m2, significantly higher in nephrology vs geriatric patients (43 vs 40 ml/min/1.73 m2). Logistic regression analyses using eGFR categorical variable > 45 ml/min/1.73 m2 instead of continuous eGFR confirmed this association, with eGFR 45–60 ml/min/1.73 m2 being the most consistent factor associated with ESA inertia across all settings in fully-adjusted models (OR 2.01, 1.51–3.01).
link