HemobloginA2 Levels Associate with Lower ESA-Dose in African-Americans with Sickle Cell Trait and End-Stage Kidney Disease

Introduction: We have previously demonstrated that African-Americans with end-stage kidney disease on hemodialysis receive higher doses of erythropoietin-stimulating agents (ESA) if they also have sickle cell trait (SCT). In sickle cell disease, the severity of clinical manifestations is modified by the quantity of hemoglobin S (HbS) expressed and attenuated by hemoglobin F (HbF) expression. Measures of hemoglobin A2 (HbA2) are reported to be higher in SCT although this may be related to testing artifact. We evaluated if ESA dosing in SCT patients on hemodialysis is associated with differences in the amount of these hemoglobins. Methods: From a cohort of 155 African-Americans on hemodialysis, we collected data on the level of hemoglobin type (HbA, HbS, HbA2, HbF) determined by cation-exchange high-pressure liquid chromatography (HPLC) studies. Only SCT individuals were included. Demographics and medical history were reviewed for covariates including age, sex, BMI, diabetes mellitus, history of gastrointestinal bleeding, vascular access type, time on dialysis and missed treatments. All laboratory studies were reviewed and averaged from a 3-month period for ferritin, iron saturation, parathyroid hormone, serum albumin, serum phosphorus, and adequacy studies (Kt/V). We calculated delivered ESA doses and intravenous iron doses as per-treatment dosing. We compared continuous measures of the amount of each hemoglobin type with ESA dose using SpearmanÕs correlation. We also constructed multivariable linear regression models using backward elimination to identify relevant confounders from a full model. Iron dosing and iron percent saturation were retained a priori. Results: 24(15%) of the 155 patients had SCT. Of the individuals excluded, 9 had hemoglobin C trait and 1 had β-thalassemia trait and the rest had normal hemoglobin variants. Median age of the 24 subjects was 62.1 years (IQR 48.7, 69.2) and 13 were male (54.2%). None had measurable HbF. Other relevant clinical and demographic data are presented in Table 1. In unadjusted analyses, percent of HbS weakly correlated with average ESA dose but was not statistically significant (ρ= -0.27, 95% -0.61, 0.15; p=0.2). HbA2 however had a relatively strong negative correlation with ESA dose that was statistically significant (ρ= -0.44, 95% CI -0.72, -0.05; p=0.03). After adjusting for age, time on dialysis, iron dose, iron percent saturation, albumin and parathyroid hormone, HbA2 still demonstrated a statistically significant negative correlation with ESA dose (p=0.04). For each tenth of percent increase in HbA2, ESA dose was lower by approximately 440 U. Conclusions: African-American hemodialysis patients with SCT receive higher doses of ESA to achieve similar hemoglobin levels as other patients. Among these individuals, higher HbA2 levels are associated with lower ESA dose even after adjustment for confounders. Although measures of HbA2 may be less accurate in SCT, these results suggest that HbA2 content may attenuate ESA resistance in this population, and further studies are needed to understand this relationship. Table 1. Demographic and clinical data in 24 African-American hemodialysis patients with sickle cell trait. Age (yrs) 62.1 (48.7, 69.2) Male sex (N, %) 13 (54.2) Body mass index (kg/m2) 26.1 (23.1, 30.7) Dialysis vintage (yrs) 6.2 (2.9, 9.3) Diabetes (N, %) 16 (66.7) Arteriovenous fistula (N,%) 14 (58.3) Hemoglobin (gm/dl) 11.9 (11.4, 12.5) HbS (%) 35.8 (31.4, 38.4) HbA2 (%) 4.1 (3.9, 4.4) Ferritin (ng/ml) 831.3 (610.7, 1121.0) Iron saturation % 29 (24.7, 37.2) iPTH (pg/ml) 451.6 (269.3, 715.2) Albumin (mg/dl) 4.0 (3.9, 4.1) Phosphorus (mg/ml) 5.7 (4.6, 6.3) Dialysis adequacy (Kt/V) 1.47 (1.35, 1.54) Counts presented as N (%). Continuous variables presented as Median and Interquartile Range (IQR) Disclosures No relevant conflicts of interest to declare.

Mental Health Symptoms, Quality of Life and Barriers to Accessing Health Care in Sickle Cell Disease

Abstract 337 Background: Individuals with sickle cell disease (SCD) face a number of barriers as they attempt to access timely and appropriate health care. We previously reported that adult and pediatric patients with SCD differed on some barriers reported, with adults citing more barriers related to insurance and provider knowledge and attitudes. Patients' emotional status, including worry, frustration and anger, were also reported barriers to accessing health care. However, there has been limited research formally assessing mental health symptoms as potential barriers to accessing health care in SCD. Objective: To investigate the relation between mental health symptoms, quality of life and reported barriers to accessing healthcare. We hypothesized that 1) mental health symptoms would be predictive of reported barriers, for adults with SCD compared with children, and 2) quality of life would be inversely related to the number of reported barriers, for adults and children. Methods: 112 patients with SCD were enrolled in a cross sectional study. Pediatric patients and their parents, and adults with SCD completed screening measures of depression (Patient Health Questionnaire-9 or Children's Depression Inventory) and anxiety (Generalized Anxiety Disorder- 7 or Multidimensional Anxiety Scale for Children-10) and were categorized with no, mild, moderate or severe symptoms. They also completed quality of life measures (SF 36v2® or PedsQL®) and a validated checklist of barriers to accessing healthcare for SCD. Results: Participants were 35 children (M age 9.5, 1– 17 years) and their parents, and 77 adults (M age 31.2, 18 – 68 years); 53% female; 75% African American; 71% diagnosed with Hgb SS. Sixty one percent of adults reported moderate to severe depressive symptoms, compared with 4% of children (p <.001). Thirty-six percent of adults reported moderate to severe symptoms of anxiety, compared with 12% of children (p <.05). Adults reported significantly worse quality of life in the Physical (M =53.0, SD =23.7) and Mental Health (M =49.4, SD =23.2) domains compared with children (Physical M =65.6, SD =21.4, p <.05 and Mental Health M =66.0, SD =17.9, p <.01). In regression analyses, we found that, with gender and hemoglobin type controlled for, depression was predictive of number of barriers faced for adult (R2 =.27, β = 3.57 ±.88, n = 74) but not pediatric patients (R2 =.26, β = 5.68 ± 2.54, n = 26). Anxiety was predictive of number of barriers faced for adults (R2 =.28, β = 3.99 ±.94, n = 75) but not pediatric patients (R2 =.13, β = 2.13 ± 1.96, n = 26). Greater number of barriers faced was predictive of worse quality of life in the Mental Health domain for both adults and pediatrics, controlling for gender and hemoglobin type (R2 =.19, β = −.98 ±.26, n = 73 for adults and R2 =.28, β = −1.06 ±.36, n = 33 for pediatrics). In the Physical domain, greater number of barriers faced was predictive of worse quality of life for adults but not pediatrics, controlling for gender and hemoglobin type (R2 =.18, β = −.97 ±.26, n = 73 for adults and R2 =.15, β = −1.03 ±.46, n = 33 for pediatrics). Conclusion: Adults with SCD reported a higher prevalence of moderate to severe symptoms of depression and anxiety, compared with children with SCD and the general African American population. Mental health symptoms were predictive of difficulties with accessing health care for adult more so than pediatric patients. There is an urgent need to address barriers to health care for patients with SCD; to prevent morbidity in pediatrics that may contribute to impaired quality of life in adulthood; and to improve mental health services available to adults in particular. Disclosures: No relevant conflicts of interest to declare.