Specific factors may predict better initial response to darbepoetin alfa in patients with nondialysis chronic kidney disease (CKD), new study findings suggest.

Japanese investigators led by Ichiei Narita, MD, of Niigata University in Niigata, Japan, conducted the BRIGHTEN study (oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa) to establish an evidence-based index of hyporesponsiveness to erythropoiesis-stimulating (ESA) agents. They tracked 1695 patients (mean age 70 years; 59% male; 28% with diabetic nephropathy) with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 (according to the Japanese equation) and renal anemia (hemoglobin [Hb] less than 11 g/dL) over 12 weeks of initial darbepoetin alfa treatment. At ESA initiation, the median creatinine level was 2.62 mg/dL and mean Hb level was 9.8 g/dL.

Darbepoetin alfa was most commonly administered 3 times (41.1%) or 4 times (15.6%) over 12 weeks with the dose ranging widely from 15 to 900 μg. Using this information, the investigators created an initial ESA response index (iEResI): a ratio of Hb changes over 12 weeks after ESA administration per weight-adjusted total dose.

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Notably, 13.3% of patients failed to respond to ESA therapy, Dr Narita and colleagues reported in Clinical and Experimental Nephrology.

Multivariate analyses showed that male gender, hypoglycemic agent use, iron supplementation (but not serum ferritin or transferrin saturation level), high eGFR, low Hb, low C-reactive protein (CRP), low N-terminal pro b-type natriuretic peptide (NT-proBNP), and low urinary protein-creatinine ratio (PCR) were independently and significantly associated with better initial response to ESA therapy (P <.0001, P =.0108, P <.0001, P =.0476, P <.0001, P =.0004, P =.0435, and P =.0009, respectively).

Of this list of factors, “Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to [darbepoetin alfa],” Dr Narita’s team stated. NT-proBNP may reflect the severity of cardiovascular disease and proteinuria the severity of kidney function decline, they noted.

The investigators are now planning future analyses that compare iEResI with the ESA resistance index (ERI) and patient outcomes.

Disclosure: This clinical trial was supported by Kyowa Kirin Co. Ltd. Please see the original reference for a full list of authors’ disclosures.


Hayashi T, Kato H, Tanabe K, et al. Initial responsiveness to darbepoetin alfa and its contributing factors in non‑dialysis chronic kidney disease patients in Japan. Clin Exp Nephrol. doi:10.1007/s10157-020-01969-7