#2654 Erythropoietin hypo-responsiveness in haemodialysis patients, contributing factors and outcome
Authors: Aggarwal Manju 
Published: May 2024

Abstract

Background and Aims
Erythropoietin (ESA) resistance or hypo-responsiveness (HR) is a condition when patients do not achieve the desired haemoglobin concentration or require incremental ESA doses to maintain stable Hb concentration. Contributing factors include iron deficiency, inflammation, infection, mineral bone disease (CKD-MBD), insufficient dialysis, malnutrition, and hematologic abnormalities. This study aimed to determine the prevalence of HR in maintenance haemodialysis (HD) population and its contributing factors. The outcome in terms of all-cause mortality and need for hospitalization over 6 months follow-up was studied.

Method
We prospectively studied 100 maintenance HD patients above 18 years age over one and a half years. Those with a known haematological disorder, malignancy or active infection were excluded.
Enrolled patients were classified into 2 groups:
1) Initial ESA Group: Initiated on ESA therapy and had Hb less than 10 gm/dl. These were also incident HD patients. Initial ESA HR for the study was defined as any Hb increase less than 0.8 gm/dl over 1 month after initiating ESA. The ESA dose and modification remained as per current existing practice in the dialysis unit. 2) Subsequent ESA Group: Already receiving ESA therapy and on HD for at least 3 months. Patients on previously stable doses of ESA who required two increments in ESA doses up to 50% beyond the previous dose to maintain Hb were taken as HR. Patients who required Epoetin or equivalent ESA dose of more than 300 IU/kg/week were also included in HR. All underwent anaemia workup at start and monthly haemoglobin estimation. They were also tested for CRP and CKD-MBD. All were followed for 6 months; hospitalization (excluding vascular access) and mortality was noted. The Charlson comorbidity index was used to ensure equitability.

Results
Seventeen cases were in Initial ESA group and 83 cases were in subsequent ESA group. ESA type was not associated with responsiveness in either group. In the ‘initial’ group, 8/17 were HR. Iron deficiency was noted in 75 and 33 percent of HR vs R patients (p =0.15). Median CRP in HR group was significantly higher at 10 mg/dL (7.4-20.4) as compared to R 2.8mg/dl (1.5-4), p=0.034. Distribution of other bio-chemical parameters was comparable. HR patients had more hospitalizations (62.5% vs 22.2%; p =0.153). In subsequent ESA group 10/83 (12%) cases were HR. Mean average weekly ESA dose (IU/Kg/week) in HR (286 ± 28) was significantly higher than R group (137 ± 44, p &lt;0.0001). Median CRP (mg/dL) in HR was 20.2 (8.8-27.6) and was significantly higher than R 2.6 (1.2-5.4, p=0.0001). Median iPTH (pg/mL) in HR group was 899 (801-1053) significantly higher than R 418 (242-632; p =&lt;0.0001). Mean serum phosphorus (mg/dL) in HR was 6.4 ± 1.7 which was significantly higher as compared to R (5.3 ± 1.6, p value=0.038). Median ALP of 366 (276-408) IU/L in HR was significantly higher than in R 126 (93-196, p=0.0007). Both groups were equitable in adequacy. Hospitalization rate was not (60 vs 30%, p=0.09) different. Mortality rate was significantly higher in HR as compared to R (40% vs 1.4%, p=0.0005).

Conclusion
The study revealed a substantial occurrence of ESA hypo-responsiveness in HD population. High CRP, signifying inflammation and CKD-MBD turned out to be significant contributors to development of hypo-responsiveness. ESA hypo-responsiveness is associated with higher mortality over short term.