The Relationship Between Depressive Symptoms and Erythropoietin Resistance in Hemodialysis Patients

Abstract

Erythropoietin deficiency is the primary cause of anemia in patients with end-stage renal disease (ESRD) and is mainly caused by a decreased erythropoietin production by the kidney. The response to treatment with ESA is dose dependent in most patients. Factors associated with ESA resistance and therefore need for higher doses of ESA include iron deficiency, chronic hyperparathyroidism, low serum albumin level, elevated aluminum level, malnutrition, suboptimal dialysis and medications, including angiotensin-converting enzyme inhibitors (Salman et al., 2012). The reported depression incidence in dialysis patients varies in different studies and this difference is said to be due to different criteria and research methodologies in diagnosing depression. Those studies which applied Beck`s Depression Inventory have similarly demonstrated that half to one third of the dialysis patients had at least some degrees of depression (score>10) (Roshanak et al., 2014). Depression is the most common psychological condition in dialysis patients as an outcome of imaginary or true loss such as losing job, income, energy, sexual potency, freedom and life expectancy. Various sources have implied a relation between depression and mortality and morbidity rate (Roshanak et al., 2014). Resistance to erythropoietin (EPO) treatment has been associated with inflammation and malnutrition in hemodialysis (HD) patients. Depression has also been associated with both inflammation and malnutrition; however, the specific relationship between depressive symptoms and EPO resistance is not known (Afsar, 2013). We aim in our study to evaluate the frequency of depression among hemodialysis patients and to study the relationship between depressive symptoms and EPO resistance. This cross sectional study was taken place in the specialized medical center of El Entag El Harby Hospital and included (90) patients on regular hemodialysis. Inclusion criteria of the patients were age ≥ 21 years, patients were on regular thrice weekly hemodialysis sessions for at least 6 months before the study, each dialysis session lasted four hours using bicarbonate dialysate, low flux dialyzers and heparin as anticoagulant, patients received erythropoietin stimulating agents (ESA) to treat anemia for at least 3 months and patients with adequate Iron stores (transferrin saturation (TSAT) of >20%, and a serum ferritin level of >100 ng/mL). Exclusion criteria were malignancy, acute infection, patients who were mentally disoriented or unconscious, mental retardation, non renal cause of anemia, evidence of active or occult bleeding and history of blood transfusion within the past 4 months. Erythropoietin resistance calculated by ERI (erythropoietin resistance index), which is defined as erythropoietin dosage (U) over a week divided by the average post-HD weight (Kg) for that week and hemoglobin (Hb) value (g/dl) (Lopez et al., 2008). The Beck depression inventory (BDI-II) test is a questionnaire consisting 21 items was used as diagnostic tool for depression. The BDI is documented as a valid index of depression and BDI scores correlate well with the diagnostic criteria for depression. Fasting serum samples were obtained. All biochemical blood samples were collected before the mid-week HD session and before heparin administration. With the exception of the post dialysis urea nitrogen post dialysis to calculate urea kinetics. Laboratory tests for all patients included complete blood cell counts, urea reduction ratio (URR=(Upre-Upost)÷Upre) (Kalender et al., 2006), serum creatinine, serum calcium, phosphate, Intact PTH level, serum ferritin, iron and total iron binding capacity (TIBC), transferrin saturation (TSAT) = serum iron/total iron binding capacity X 100, CRP titer and albumin. Our study recorded that 17 (18.9%) of the patients were females and 73 (81.1%) were males with mean age was 58.97±11.16 year, duration of hemodialysis was 39.51±31.05 month and the mean of erythropoietin dose per weak 9777.77±3179.20 IU/W. We measured erythropoietin resistant index (ERI) in all patients which was 12.73±5.12 IU/kg/wk. In this study the patients were divided into four groups regarding erythropoietin resistance: Group I included 22 (24.4%) patients with ERI less than 25th percentile (< 9.045). Group II included 23(25.5%) patients with ERI from 25th percentile up to less than 50th percentile (9.045 - < 13.700), Group III: ERI from 50th percentile up to 75th percentile (13.700 – 16.325) included 23 (25.5%) patients and Group IV: more than 75th percentile (> 16.325), which included 22 (24.4%) patients (the higher resistant group). We also revealed a significant difference between the studied groups regarding BMI (P value <0.05) and post hoc analysis showed that significance is between group 4 and the other three groups. There is significant correlation between ERI and BMI (r=-.25, p>.016). BMI is independent factor by linear regression (P value<0.05). Our current study recorded a significant difference between the studied groups regarding sex (P value <0.05), however linear regression between ERI with sex was insignificant value (P value>0.05). The fourth quartile percentage of male was 100% (N=22), which was more hyporesponsive.