Definitions of hyporesponsiveness to ESAs
| Definitions of ESA hyporesponsiveness . | Organization or study . |
|---|---|
| Failure to attain the target Hb concentration while receiving >300 IU/kg/wk (20 000 IU/wk) of epoetin or 1.5 µg/kg of darbepoetin alfa (100 µg/wk), or a continued need for such high dosages to maintain the target | Revised EBPG, ERA-EDTA, 200468 |
| Initial ESA hyporesponsiveness: • if no increase in Hb concentration from baseline after the first month of ESA treatment on appropriate weight-based dosing Subsequent ESA hyporesponsiveness: • classify patients as having acquired ESA hyporesponsiveness if after treatment with stable doses of ESA, they require 2 increases in ESA doses up to 50% beyond the dose at which they had maintained a stable Hb concentration | KDIGO, 20122 |
| Failure to achieve Hb target: HD patients: despite 3000 IU dose of IV rHuEPO 3 × wk (9000 IU/wk) or 60 µg/wk of IV darbepoetin alfa once per week PD patients: despite 6000 IU dose of SC rHuEPO once per week (6000 IU/wk) or 60 µg/wk of IV darbepoetin alfa once per week Predialysis CKD patients: despite 6000 IU dose of SC HuEPO once per week (6000 IU/wk) | Japanese Society for Dialysis Therapy, 201569 |
| Failure to achieve target Hb levels with epoetin doses > • IV EPO 450 IU/kg/wk • SC EPO: 300 IU/kg/wk • darbepoetin dose >1.5 µg/kg/wk | The Renal Association, UK, 2017 and 202070 |
| Weight-adjusted ERI [weekly ESA dose/(body weight × Hb)] ESA resistance: ERI >15.4 IU/kg × g/dL (quartile IV)a | Panichi et al, RISCAVID study, 201152 |
| Definitions of ESA hyporesponsiveness . | Organization or study . |
|---|---|
| Failure to attain the target Hb concentration while receiving >300 IU/kg/wk (20 000 IU/wk) of epoetin or 1.5 µg/kg of darbepoetin alfa (100 µg/wk), or a continued need for such high dosages to maintain the target | Revised EBPG, ERA-EDTA, 200468 |
| Initial ESA hyporesponsiveness: • if no increase in Hb concentration from baseline after the first month of ESA treatment on appropriate weight-based dosing Subsequent ESA hyporesponsiveness: • classify patients as having acquired ESA hyporesponsiveness if after treatment with stable doses of ESA, they require 2 increases in ESA doses up to 50% beyond the dose at which they had maintained a stable Hb concentration | KDIGO, 20122 |
| Failure to achieve Hb target: HD patients: despite 3000 IU dose of IV rHuEPO 3 × wk (9000 IU/wk) or 60 µg/wk of IV darbepoetin alfa once per week PD patients: despite 6000 IU dose of SC rHuEPO once per week (6000 IU/wk) or 60 µg/wk of IV darbepoetin alfa once per week Predialysis CKD patients: despite 6000 IU dose of SC HuEPO once per week (6000 IU/wk) | Japanese Society for Dialysis Therapy, 201569 |
| Failure to achieve target Hb levels with epoetin doses > • IV EPO 450 IU/kg/wk • SC EPO: 300 IU/kg/wk • darbepoetin dose >1.5 µg/kg/wk | The Renal Association, UK, 2017 and 202070 |
| Weight-adjusted ERI [weekly ESA dose/(body weight × Hb)] ESA resistance: ERI >15.4 IU/kg × g/dL (quartile IV)a | Panichi et al, RISCAVID study, 201152 |
Shown are examples of regional guideline definitions based on numerical threshold values. Also shown is a hyporesponsiveness definition based on the ERI. In the RISCAVID study, IL-6 was the best predictor for ESA resistance. Patients in quartile 4 were defined as hyporesponders. In this study, quartile 4 was associated with worse cardiovascular outcome and higher mortality.
Thresholds to meet the definition of ESA hyporesponsiveness vary between different studies that use the ERI.
EBPG, European best practice guidelines; ERI, ESA resistance index; ERA-EDTA, European Renal Association-European Dialysis and Transplantation Association; KDIGO, Kidney Disease: Improving Global Outcomes; PD, peritoneal dialysis; rHuEPO, recombinant human erythropoietin; SC, subcutaneous.