A new guideline from the Kidney Disease: Improving Global Outcomes (KDIGO) group provides updated recommendations on the management of anemia in chronic kidney disease (CKD), reflecting substantial advances since the previous guideline was published in 2012.

“This guideline represents a major step forward in how we approach anemia in CKD,” said Guideline co-chair Jodie Babitt, MD, of the Department of Nephrology at Massachusetts General Hospital in Boston, in a press statement.

“Importantly, the guideline integrates new evidence on emerging therapies while reinforcing the need to avoid overtreatment and to prioritize safety and shared decision-making,” Babitt added.

Management algorithms from the guideline were published in an accompanying executive summary in Kidney International.

First Guideline Update in Over a Decade

Anemia is a common complication of CKD, affecting more than half of the patients with stage 4 and 5 disease. It is associated with increased risks for cardiovascular complications, cognitive impairment, dependency on red blood cell (RBC) infusions, and mortality.

Since KDIGO’s prior guideline was released, significant changes have occurred in the understanding and management of CKD-related anemia, particularly regarding the risks and benefits of erythropoiesis-stimulating agents (ESAs), long a cornerstone of treatment.

Other advances include improved understanding of intravenous (IV) iron use and the introduction of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) as alternatives to ESAs. However, concerns remain regarding the long-term risks and benefits of these newer agents as compared with ESAs.

To address these and other issues, KDIGO convened an international, multidisciplinary work group, supported by an evidence review team, to develop the updated guideline.

The resulting recommendations are organized into four chapters covering diagnosis and evaluation, use of iron, ESA therapy, and RBC transfusion. These recommendations are based on graded evidence from systematic reviews. Additional practice points are included to provide clinical guidance from experts where evidence is relatively limited.

The Optimal Use of Iron

For iron therapy in CKD-related anemia, KDIGO recommended initiating iron therapy in patients with stage 5 CKD receiving hemodialysis when ferritin levels are ≤ 500 ng/mL (≤ 500 µg/L) and transferring saturation (TSAT) is ≤ 30%.

In this population, IV iron is recommended over oral iron.

“In people with stage 5 CKD and anemia on hemodialysis in whom iron therapy is being initiated, administer IV iron using a proactive approach to maintain stable iron status,” the authors suggested in a practice point.

For patients with CKD and anemia not receiving dialysis, or those with stage 5 CKD receiving peritoneal dialysis, iron therapy is recommended when either of the following criteria are met:

• Ferritin < 100 ng/mL (< 100 µg/L) and TSAT < 40%, or
• Ferritin ≥ 100 ng/mL (≥ 100 µg/L) and < 300 ng/mL (< 300 µg/L), with TSAT < 25%.

For those with anemia and CKD not receiving hemodialysis, the guideline recommended choosing oral or IV iron based on patient values and preferences, severity of anemia and iron deficiency, and the relative efficacy, tolerability, availability, and cost of each option.

Guidance on ESAs and HIF-PHIs

The guidelines recommend ESAs as a first-line therapy over HIF-PHIs for CKD-related anemia after correctable causes of anemia have been addressed.

“In people with anemia and CKD, HIF-PHIs should be avoided in those at increased risk for adverse events,” the authors noted in a practice point.

For patients with CKD receiving hemodialysis, ESA therapy should be initiated when the hemoglobin (Hb) concentration is ≤ 9.0-10.0 g/dL (≤ 90-100 g/L).

Among patients with CKD not receiving dialysis, including kidney transplant recipients and children, the selection of an Hb concentration at which ESA therapy is initiated “should consider the presence of symptoms attributable to anemia, the potential benefits of higher Hb level, and the potential harms of RBC transfusions or ESA therapy,” the authors wrote.

For ESA maintenance therapy, the guideline recommended targeting an Hb level below 11.5 g/dL (115 g/L).

Although HIF-PHIs have been postulated to improve iron availability and reduce iron treatment requirements, the authors noted that there are insufficient data to recommend different thresholds for patients treated with HIF-PHIs compared with ESAs.

The guideline identified two key clinical scenarios in which HIF-PHIs may be considered: ESA hyporesponsiveness or intolerance, and situations in which ESA use is impractical, such as when there are barriers to parenteral administration.

However, the authors emphasized that the safety and efficacy of HIF-PHIs in patients with ESA hyporesponsiveness have not been established.

RBC Infusions

Although KDIGO issued no formal recommendations regarding RBC transfusions, the guideline’s practice points endorsed their use as part of a comprehensive treatment strategy, with careful consideration of risks and benefits through shared decision-making.

Among transplant-eligible patients with CKD, the guideline advised avoiding RBC transfusions when possible to minimize the risk for allosensitization.

The decision to transfuse patients with anemia and CKD should be made “based on the symptoms and signs caused by anemia instead of an arbitrary Hb threshold,” the guideline authors noted.

For patients with CKD and acute anemia, RBC transfusion should be considered when potential benefits outweigh the risks, including when rapid correction of anemia is required to stabilize the patient’s condition, such as with acute hemorrhage, unstable coronary artery disease, or urgent preoperative needs.

Targeted to a Global Audience

The guideline, based on a “rigorous synthesis of the latest evidence, clearly differentiates opinion from evidence-based recommendations, and will be applicable to a global audience practicing in a very wide range of settings,” co-chair Marcello Tonelli, MD, of the Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, told Medscape Medical News.

Compared with the previous guidance, Tonelli noted, the update features “more emphasis on shared decision-making for when to initiate ESA and what Hb level to target, and more details on the factors that could influence these decisions.”

At the same time, he emphasized that important knowledge gaps remain, particularly regarding optimal use of HIF-PHIs.

Ultimately, “we hope that the guideline helps clinicians to understand when and how to incorporate the preferences of patients and families into decisions about treating the anemia of kidney disease and kidney failure,” Tonelli said.

Tonelli reported having no disclosures. The other authors’ disclosures are detailed in the published guideline.