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Kidney Week

Abstract: PO0295

Hemoglobin Requirements of Clinical Trials Involving Anemia in CKD and Implications on Future Work: A Systematic Literature Review

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Farag, Youssef MK, Akebia Therapeutics, Inc., Cambridge, Massachusetts, United States
  • Langford, Bryony, Symmetron Ltd., London, United Kingdom
  • Yasmeen, Najeeda, Symmetron Ltd., London, United Kingdom
  • Sawyer, Laura M., Symmetron Ltd., London, United Kingdom
  • Sanon, Myrlene, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey, United States
  • Wang, Xinyu, Otsuka Pharmaceutical Europe Ltd., Slough, United Kingdom
  • Mccormick, Linda, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey, United States
  • Michalopoulos, Efstathios N., Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey, United States
Background

Anemia is a common complication in patients with chronic kidney disease (CKD), contributing to reduced quality of life and increased risk of morbidity and mortality. Erythropoiesis-stimulating agents (ESAs) are the established standard of care for anemia management in CKD patients. This review examines hemoglobin (Hb) requirements in randomized controlled trials (RCTs) of ESAs as treatment of anemia in CKD.

Methods

Embase, Medline, and Cochrane Library were searched from 1946 to November 2019 for RCTs evaluating the safety and efficacy of ESAs as treatment for adults with anemia and CKD. Descriptive analyses were performed to assess between-trial differences with respect to baseline Hb and Hb target ranges. Studies were classified by dialysis status (non-dialysis-dependent [NDD] vs dialysis-dependent [DD] vs renal transplant recipient [RTR]), and by treatment goal (correction vs conversion).

Results

Searches retrieved 3,482 records, from which 57 trials met the inclusion criteria. Thirty-seven studies reported a Hb target, including 15 correction studies (NDD, 11; DD, 3; RTR, 1), 19 conversion studies (NDD, 2; DD, 16; RTR, 1) and 3 that were mixed/unclear (DD, 2; NDD/DD, 1). The unweighted medians (range) of the mean baseline Hb in correction and conversion studies were 10.1 g/dL (7.0-11.7) and 11.2 g/dL (9.8-12.1), respectively. There were 20 different Hb target ranges used to assess efficacy; 10-12 g/dL was utilized most often (n=8). Three of 37 RCTs used a singular Hb target threshold, whilst the remaining studies used a Hb target range, which varied from narrow (0.5 g/dL) to wide (5.0 g/dL) between the lower and upper limits. Target Hb ranges used an upper limit of >12 g/dL in 21/37 RCTs (correction, 11/15; conversion, 10/19); however, only 3/21 RCTs were published after 2012 (the last update of KDIGO Clinical Practice Guideline).

Conclusion

This systematic review shows that changing Hb requirements over time are a source of difference in RCTs of ESAs for treatment of anemia in CKD. Such differences may introduce bias when using quantitative synthesis methods (e.g. network meta-analysis) to assess the comparative efficacy and safety of ESAs relative to new treatment options.

Funding

  • Commercial Support