Last year’s ASN Kidney Week Congress featured a range of presentations related to the management of iron deficiency anemia in non-dialysis CKD (ND-CKD). In this article we summarise some of the key findings from these studies.
Approximately half of Medicare stage 3-5 ND-CKD patients have anemia
In order to understand the prevalence and treatment patterns of anemia in ND-CKD patients, Dr Wendy St. Peter and colleagues analysed information from the Medicare and MarketScan databases. They found that:
- 52% of patients over 65 from the Medicare database were anemic (ranging from 46% of patients with stage 3 to 74% with stage 5), and
- 28% of 18-64 year olds in the MarketScan database were anemic (ranging from 22% of those with stage 3 to 54% with stage 5).
RBC transfusions were the most common treatment in these populations, followed by ESA therapy and IV iron. Dr St. Peter et al. also reported an increase in major adverse cardiac events and thromboembolic events with disease stage. A higher rate of CV events occurred in patients with anemia compared to those without.
In another study, Dr St. Peter again used US Medicare data to compare anemia management practices in non-dialysis patients before and after the publication of the TREAT study, FDA changes to warnings on ESA labels and the KDIGO anemia treatment guideline update. ESA use declined by 57% between the two cohorts (2008 and 2012), while transfusion and IV iron use remained stable. However, the decrease in ESA use was associated with earlier administration of transfusions.
Can physicians identify patients who may respond to iron therapy after an initial period of non-response?
Effective treatment of anemia in chronic kidney disease patients is important for optimal disease management. Being able to identify patients who may respond to iron therapy after an initial period of non-response could help inform treatment decisions, preventing long periods of anaemia.
FIND-CKD was a large randomised controlled trial of IV ferric carboxymaltose treatment to high or low ferritin targets vs oral iron. Using data from the study, Professor Iain Macdougall and colleagues:
- Identified responders to treatment at week 4,
- Assessed the percentage of those non-responders who had responded to treatment by week 8, and
- Examined baseline characteristics to see if non-responders at week 8 could be identified sooner.
The results are outlined in the table beneath.
|Oral iron||High ferritin FCM||Low ferritin FCM|
|Hb response at Week 4, (%)*||22%||41%||14%|
|Hb response at Week 8 in week 4 non-responders (%)*||11%||32%||16%|
|Baseline values: Week 4 responders vs non-responders|
|Mean Hb, g/dL||9.9 vs 10.5||10.1 vs 10.5||9.8 vs 10.5|
|Mean ferritin, ug/L||37 vs 61||41 vs 65||37 vs 57|
|TSAT, %||12 vs 17||12 vs 19||15 vs 16|
*Excluding patients with rescue therapy
Based on these results, the authors hypothesised that earlier intervention for patients who are not responding to oral iron therapy may improve anaemia management, although further studies are needed to assess the predictive ability of baseline parameters.
New anaemia treatments under development for ND-CKD patients
Over the four days of the Congress, data were also presented regarding hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF inhibitors). Two industry symposia provided the background on these new therapies, while poster presentations reported positive effects of HIF inhibitors on haemoglobin levels in ND-CKD patients with anaemia. [4-6] Multiple Phase 3 trials are ongoing.
Four posters reported results from a Phase 3 trial of the iron-based phosphate-binder, ferric citrate, evaluating its efficacy as a treatment for iron deficiency anemia in ND-CKD patients. In a 16-week study, patients receiving ferric citrate had significant improvements in haemoglobin and reductions in serum phosphate compared to placebo. Ferric citrate was also considered to be well tolerated.[7-10] During an industry-sponsored symposium, the potential use of ferric citrate as an alternative to oral iron in situations of non-acute iron deficiency was discussed.
- Abstract: [FR-PO766] Anemia Prevalence and Treatment in Patients with Non-Dialysis-Dependent Chronic Kidney Disease. http://www.abstracts2view.com/asn_2016/view.php?nu=391&terms=&type=abstract
- Abstract: [FR-PO767] Anemia Treatment Pattern Changes in Non-Dialysis-Dependent Chronic Kidney Disease Patients before and after Revised Food and Drug Administration Label and New Anemia Guidelines for Erythropoiesis-Stimulating Agents. http://www.abstracts2view.com/asn_2016/view.php?nu=3485&terms=&type=abstract
- Abstract: [TH-PO906] Low Rate of Early Response to Oral Iron in Patients with Non-Dialysis Dependent CKD (ND-CKD). http://www.abstracts2view.com/asn_2016/view.php?nu=1257&terms=&type=abstract
- Abstract: [TH-PO907] Efficacy and Dose Requirements of Vadadustat Are Independent of Systemic Inflammation and prior Erythropoiesis-Stimulating Agent (ESA) Dose in Patients with Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD). http://www.abstracts2view.com/asn_2016/view.php?nu=5060&terms=&type=abstract
- Abstract: [TH-PO908] Daprodustat, a HIF-Prolyl-Hydroxylase Inhibitor, Increases and Maintains Hemoglobin over 24 Weeks in Anemic Chronic Kidney Disease Subjects. http://www.abstracts2view.com/asn_2016/view.php?nu=3961&terms=&type=abstract
- Abstract: [TH-PO960] Vadadustat Maintains Hemoglobin (Hb) Levels in Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Patients Independent of Systemic Inflammation or prior Dose of Erythropoiesis-Stimulating Agent (ESA). http://www.abstracts2view.com/asn_2016/view.php?nu=5308&terms=&type=abstract
- Abstract: [TH-PO901] Effects of Ferric Citrate (FC) in Adults with Non-Dialysis-Dependent Chronic Kidney Disease and Iron-Deficiency Anemia (IDA): Ph 3 Clinical Trial. http://www.abstracts2view.com/asn_2016/view.php?nu=2200&terms=&type=abstract
- Abstract: [TH-PO902] Hemoglobin Response to Ferric Citrate (FC) in Subjects with Non-Dialysis Dependent (NDD) Chronic Kidney Disease (CKD) and Iron Deficiency Anemia (IDA): Data from a Phase 3 Clinical Trial. http://www.abstracts2view.com/asn_2016/view.php?nu=3705&terms=&type=abstract
- Abstract: [TH-PO903] Effects of Ferric Citrate on Parameters of Mineral and Bone Metabolism in Patients with Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) Treated for Iron Deficiency Anemia (IDA). http://www.abstracts2view.com/asn_2016/view.php?nu=3429&terms=&type=abstract
- Abstract: [TH-PO904] Predictors of Hemoglobin Response to Ferric Citrate in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Iron Deficiency Anemia. http://www.abstracts2view.com/asn_2016/view.php?nu=3937&terms=&type=abstract