Hyporesponse Results in More Adverse Events for CKD Patients With Anemia

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Acute inpatient admission was higher in patients with persistent hyporesponse, compared to patients with acute hyporesponse or without hyporesponse.

Erythropoiesis-stimulating agents (ESA) are some of the more common treatments for patients with anemia caused by chronic kidney disease (CKD). However, hyporesponse to this family of drugs is linked to a number of adverse events and negative outcomes.1

A team, led by Christine Ferro, Milliman, compared the rates of acute inpatient admission, 30-day readmission, and mortality between Medicare patients with and without hyporesponse to ESAs.

Three Patient Groups

In the study, the investigators examined patients who were treated with at least 6 months of outpatient dialysis with concurrent ESA use in 2019 using data from 100% of Medicare fee-for-service beneficiaries. Each patient was stratified by dialysis modality, including hemodialysis only, peritoneal dialysis only, and multiple modalities.

The final analysis included 206,670 patients, 10.3% (n = 21,302) who met the definition for hyporesponse, which was defined as patients with at least 2 consecutive months where the mean ESA weekly dose surpassed 300 epoetin alf units per kg of body weight and patients hemoglobin level in the prior month was less than 10 g/dL.

Each patient was classified based on the portion of months flagged as acute hyporesponse if less than 60% and persistent hyporesponse greater than or equal to 60%.The rates of AIP admission and 30-day all-cause readmission per patient per year were risk-normalized and mortality was calculated as the percentage of patients who died in 2019.


The results show 92% of patients were treated with hemodialysis, while 6% had peritoneal dialysis and 2% were in the multiple modality group.

Acute inpatient admission was higher in patients with persistent hyporesponse (2.9, 1.7, and 3.3 admits for patients receiving HD, PD, and HD+PD), compared to patients with acute hyporesponse (2.3, 1.6, and 3.2) or without hyporesponse (1.2, 1.0, and 2.1).

The investigators noticed a similar pattern for readmission rates.

Mortality Rates

Moreover, mortality rates increased in the hyporesponse group (6.1%–8.0% for patients without hyporesponse, 8.8%–12.9% for acute hyporesponse, and 10.0%–23.9% for persistent hyporesponse).

Patients in the peritoneal dialysis group had the lowest rates of all metrics across the different levels of hyporesponse to ESA.

“Rates of adverse events increase with persistence of hyporesponse,” the authors wrote. “Among patients receiving [hemodialysis], those with persistent hyporesponse experienced rates of acute inpatient admits and readmits about 100% higher and mortality rates almost 200% higher (23.9%) than patients without hyporesponse (8.0%).”

The results indicate patients with hyporesponse utilize more health care resources and there remains a need to develop alternative anemia therapies in order to drive down costs.

A New Drug

There also is a need to consider quality of life enhancements when developing new drugs for patients with CKD.

During the American Society of Nephrology’s Kidney Week, investigators presented new data showing daprodustat resulted in improvements in hemoglobin, as well as increases in vitality scores for fatigue in adult patients with anemia of CKD.

The data came from the phase 3 ASCEND trial of 614 non-dialysis dependent patients with CKD. The results show a greater proportion of patients treated with daprodustat had at least a 1 g/dl increase in hemoglobin from baseline (77% vs 18%; <0.001), while the adjusted mean SF-36 Vitality score increased by 7.3 points in the daprodustat group compared to 1.9 points in the placebo group.

In an interview with HCPLive®, Kirsten L. Johansen, MD, Hennepin Healthcare, University of Minnesota, explained why it is so challenging to treat diseases, while simultaneously addressing fatigue issues for the patients.