Anemia in CKD: what KDIGO 2026 changed

A 68-year-old man with stage G4 chronic kidney disease due to diabetic nephropathy comes to the visit tired and short of breath on moderate exertion. In a fictional case like this, hemoglobin falls by about 2 g/dl in six months and reaches just over 9 g/dl. Ferritin is 180 ng/ml and transferrin saturation is 18. The physician following him must decide whether to replace iron, start an erythropoiesis-stimulating agent, investigate bleeding, or do all of these at the same time.

The KDIGO guideline on anemia in chronic kidney disease, published in 2026, was the first complete revision of the topic since 2012 (KDIGO Anemia Work Group, 2026). Over more than a decade, the prolyl hydroxylase inhibitors of hypoxia-inducible factor (the HIF-PHIs) arrived, along with new trials of intravenous iron and a more careful reading of the risks of pursuing high hemoglobin. The document reorganized all of this into four chapters: diagnosis, iron, erythropoiesis-stimulating agents and transfusion.

This text follows the guideline's reasoning in the order in which it appears in the office and in the dialysis unit. The classification of chronic kidney disease by filtration rate and albuminuria is left for the text on KDIGO 2024; here the focus is anemia.

Key points

• KDIGO 2026 replaces absolute iron deficiency with systemic iron deficiency, and functional deficiency with iron-restricted erythropoiesis (KDIGO Anemia Work Group, 2026).
• Initial screening became leaner: complete blood count, reticulocytes, ferritin and transferrin saturation.
• Outside hemodialysis, iron is now suggested with ferritin below 100 and saturation below 40, or ferritin between 100 and 300 with saturation below 25.
• In hemodialysis, intravenous iron is given proactively with ferritin up to 500 and saturation up to 30.
• Once reversible causes are corrected, the erythropoiesis-stimulating agent is the first choice, ahead of the HIF-PHI.
• In treated adults, the goal is to keep hemoglobin below 11.5 g/dl (KDIGO Anemia Work Group, 2026).
• Transfusion is decided by symptoms, and those who can receive a transplant should be spared it whenever possible.

Summary

• Why anemia in CKD is a reasoning problem
• Diagnosis: what to order and how often
• Iron: new names and new thresholds
• Intravenous iron in practice
• ESA or HIF-PHI: the first choice
• Hyporesponse: when treatment does not work
• Transfusion: symptoms, transplant and what to avoid
• How NEXO helps train this reasoning
• Frequently asked questions
• Take-home messages

Why anemia in CKD is a reasoning problem

Anemia is one of the most common complications of chronic kidney disease and becomes more frequent as filtration falls. The classic explanation is insufficient erythropoietin production by the diseased kidney, but the guideline insists that it rarely acts alone (KDIGO Anemia Work Group, 2026). Chronic inflammation raises hepcidin, which locks iron in the stores and reduces intestinal absorption. Blood losses on dialysis, frequent blood draws and phosphate binders complete the picture.

An anemia that hides others

In practice, the risk is attributing all anemia to the kidney. KDIGO's figure of reversible causes lists iron, vitamin B12 and folate deficiency, hypothyroidism, hyperparathyroidism, gastrointestinal bleeding, hemolysis, infection, malnutrition, inadequate dialysis, cancer and bone marrow diseases. Each one changes management. The patient with myeloma, for example, may come to the visit with anemia and kidney failure at the same time, and kidney care in myeloma depends on recognizing the underlying disease early.

What the decade brought

Between 2012 and 2026, three groups of evidence changed the topic. The trials with high hemoglobin targets, such as TREAT, CHOIR and CREATE, showed more stroke and cardiovascular events without a survival gain, and were the basis for the lower target already in 2012. Then came the studies of proactive intravenous iron in hemodialysis, such as PIVOTAL, and the large phase 3 programs of the HIF-PHIs, such as the ASCEND studies with daprodustat and the INNO2VATE studies with vadadustat (KDIGO Anemia Work Group, 2026).

A Canadian cohort of nearly 29,000 patients helps to understand the effect of this history. Between 2007 and 2017, mean hemoglobin fell from 12.2 to 11.3 g/dl, use of an erythropoiesis-stimulating agent declined, and the chance of having hemoglobin below 9 g/dl increased each year (Birks et al., 2026). Only a minority of patients fit the criteria of the trials that motivated the caution (Birks et al., 2026). The 2026 guideline tries to correct this excess of conservatism without returning to high targets.

Diagnosis: what to order and how often

KDIGO recommends looking for anemia at referral, throughout follow-up and whenever symptoms suggest it. The initial panel became leaner: complete blood count, reticulocytes with production index, ferritin and transferrin saturation (practice point 1.2.1). Anemia remains defined by hemoglobin below 13 g/dl in men and below 12 g/dl in women (KDIGO Anemia Work Group, 2026).

The minimum frequency

The guideline suggests measuring hemoglobin at least once a year in stage G3, twice a year in G4 and every three months in G5 or on dialysis. Those using an erythropoiesis-stimulating agent or a HIF-PHI, those below target and those with rapid loss of function need closer monitoring.

When to broaden the investigation

Vitamin B12 and folate are no longer part of the mandatory initial screening. The commentary from the European Renal Best Practice Association (ERBP) calls attention to this and recalls that folate is removed by dialysis and may fall during treatment with an erythropoiesis-stimulating agent (Del Vecchio et al., 2026). If the first set of tests does not explain the anemia, KDIGO suggests broadening the search: blood smear, haptoglobin, lactate dehydrogenase, C-reactive protein, B12, folate, liver function, protein electrophoresis with immunofixation, free light chains, thyroid-stimulating hormone, parathyroid hormone and fecal occult blood (practice point 1.2.2).

The list works as an exercise in differential diagnosis: serious causes, such as cancer, hemolysis and myeloma, come in early. A similar lesson appears in chronic kidney disease of unknown cause, in which a normal test can mislead those who do not ask about the history.

Very low iron calls for a search for bleeding

With ferritin below 45 ng/ml, or with microcytic anemia without another explanation, the guideline calls for evaluation of blood loss and, if needed, referral to a gastroenterologist, gynecologist or urologist (practice point 1.2.3). The reasoning is simple: the kidney explains the lack of erythropoietin, but it rarely explains an empty iron store.

Iron: new names and new thresholds

The change in nomenclature is the first novelty of the iron chapter. Absolute iron deficiency is now called systemic iron deficiency, because the body's stores are in fact low. Functional deficiency became iron-restricted erythropoiesis, because the stores may even exist, but the iron is held by hepcidin and does not reach the marrow (KDIGO Anemia Work Group, 2026). The new names describe better what happens and help explain why a normal ferritin can coexist with a lack of iron to make red cells.

On hemodialysis

For those on hemodialysis, recommendation 2.1 suggests starting iron with ferritin up to 500 ng/ml and transferrin saturation up to 30, and recommendation 2.2 prefers the intravenous route over the oral one, both with grade 2D. Practice point 2.1 calls for a proactive strategy, with scheduled replacement to keep the store stable, and not only reactive when the tests fall. The idea comes from the PIVOTAL trial, cited by the guideline, in which the proactive regimen reduced the need for an erythropoiesis-stimulating agent without an increase in infections.

A Hungarian study shows that the proactive regimen is not always enough. In 91 patients with complete data at a hemodialysis unit, more than half remained with low saturation despite scheduled weekly iron; when the team added extra replacements guided by the tests, hemoglobin and saturation rose within three months with the same erythropoiesis-stimulating agent (Pribelszki et al., 2026).

Outside hemodialysis

For people who are not on dialysis or are on peritoneal dialysis, recommendation 2.3 suggests iron in two situations: ferritin below 100 ng/ml with saturation below 40, or ferritin between 100 and 300 ng/ml with saturation below 25. The choice between the oral and intravenous routes (recommendation 2.4) depends on patient preferences, the severity of the anemia and the deficiency, efficacy, tolerance and the availability of each option.

The patient in the opening case, with ferritin of 180 and saturation of 18, falls into the second group and has an indication for iron before considering any other agent.

Iron deficiency without anemia

Practice point 2.11 suggests considering iron even without anemia when the deficiency is profound, with ferritin below 30 and saturation below 20. ERBP agrees with this position, but notes that studies showing clinical benefit at the higher thresholds of recommendation 2.3 when there is no anemia are lacking (Del Vecchio et al., 2026). A systematic review of six studies in chronic kidney disease not on dialysis found improvement in saturation and ferritin with intravenous iron, but no gain measured in the six-minute walk test or in quality of life (Spencer et al., 2026).

When to stop

The guideline considers it reasonable to stop routine iron with ferritin above 700 ng/ml or saturation of 40 or more (practice point 2.2), and to consider a temporary pause during a systemic infection (practice point 2.8). Hemoglobin, ferritin and saturation checks should take place every three months outside hemodialysis and every one to three months on hemodialysis, with extra tests after bleeding, hospitalization or starting a stimulating agent.

Intravenous iron in practice

Switching from the oral to the intravenous route is indicated when a well-conducted oral regimen fails after one to three months or when the patient does not tolerate it (practice point 2.7). The choice of intravenous formulation follows patient preference, safety, availability and the logistics of administration (KDIGO Anemia Work Group, 2026).

Reactions and preparation

Practice point 2.9 overturns some old habits. Intravenous iron should only be given where there is capacity to treat hypersensitivity and hypotension. Premedication with a corticosteroid or antihistamine is no longer routine, and neither is a test dose, because the absence of a reaction to the test does not predict the risk. The guideline provides a flowchart by severity: nonspecific symptoms call for stopping the infusion, observing and resuming more slowly; a severe reaction, with wheezing, stridor or hypotension, calls for intramuscular adrenaline, oxygen, fluids, hospitalization and permanent discontinuation of intravenous iron.

The phosphorus that falls

A less remembered effect is hypophosphatemia. The KDIGO formulations table records the risk with ferric carboxymaltose, especially in people with early kidney disease and in kidney transplant recipients. A meta-analysis of three randomized trials found a risk of hypophosphatemia at five to six weeks about eight times higher with carboxymaltose than with ferric derisomaltose, and the severe form occurred only in the first group (Dangre et al., 2026). For those who receive iron repeatedly, measuring phosphorus is part of follow-up.

ESA or HIF-PHI: the first choice

Before any stimulating agent, KDIGO calls for correcting the reversible causes of anemia, starting with iron (practice point 3.1.2). The decision to treat to raise hemoglobin is shared with the patient, weighing symptoms, the risk of transfusions and the risk of stroke, cardiovascular events and cancer (practice point 3.1.1).

The stimulating agent comes first

Recommendation 3.1.1 suggests using an erythropoiesis-stimulating agent, and not a HIF-PHI, as first line (grade 2D). The rationale is the long experience with injectable agents and the lack of proof that the tablets are safer (KDIGO Anemia Work Group, 2026). Practice point 3.1.3 lists who should avoid HIF-PHIs: active or recent cancer, polycystic kidney disease, proliferative retinopathy, pulmonary hypertension, pregnancy, previous cardiovascular or thromboembolic events, vascular access thrombosis and liver disease.

What the HIF-PHI studies show

Recent meta-analyses help show the size of the effect. A review of 36 trials with more than 27,000 patients showed that HIF-PHIs reduced the need for transfusion compared with controls, without a significant increase in major cardiovascular events or death, with a signal of hyperkalemia outside dialysis (Huang et al., 2026). A network meta-analysis of 46 trials placed roxadustat at the top for hemoglobin elevation, but also among those with the most adverse events outside dialysis, while the stimulating agent had the lowest risk in that group (Niu et al., 2026).

In peritoneal dialysis, the ASCEND-D subanalysis with 340 patients found a similar hemoglobin response and similar cardiovascular events between daprodustat and darbepoetin, with no difference in peritonitis (Dasgupta et al., 2025). A win ratio analysis of the INNO2VATE trials, with almost 3,900 patients on dialysis, found similar mortality and hospitalizations between vadadustat and darbepoetin (Chertow et al., 2026). In Japan, a national cohort of patients with heart failure outside dialysis showed no more hospitalizations for heart failure with HIF-PHIs than with the stimulating agent (Kunitsu et al., 2026).

The body of evidence suggests equivalence across several outcomes, but with short follow-up for cancer and retinopathy, which are the biological doubts about blocking hypoxia-inducible factor. That is why the guideline left the pill as a second option.

When to start and how far to go

In dialysis, recommendation 3.2.1 suggests starting the stimulating agent with hemoglobin between 9.0 and 10.0 g/dl or less (KDIGO Anemia Work Group, 2026). Outside dialysis, including transplant recipients and children, when to start depends on symptoms, the expected benefit and the risk of transfusion or of the treatment itself (recommendation 3.2.2). In treated adults, recommendation 3.3.1, the only grade 1 recommendation in the chapter, calls for keeping hemoglobin below 11.5 g/dl (KDIGO Anemia Work Group, 2026). For HIF-PHIs, the guideline suggests using the same thresholds.

Adjustments and monitoring

After starting or changing the regimen, hemoglobin should be measured every two to four weeks, avoiding rises above 1 g/dl in that interval. Adjustments should not be made at intervals shorter than four weeks, except when hemoglobin rises too fast right at the start, in which case the amount should drop by 25 to 50 percent (KDIGO Anemia Work Group, 2026). During maintenance, monitoring becomes quarterly. The stimulating agent should be suspended during hospitalization for acute stroke, access thrombosis or a thromboembolic event. The subcutaneous route is the indicated one outside hemodialysis.

For HIF-PHIs, the guideline calls for measuring hemoglobin two to four weeks after starting and then every four weeks, monitoring the thyroid in the first three months of roxadustat and stopping the drug if there is no response within three to four months. Stimulating agent and HIF-PHI together are not allowed.

Table: from tests to management

Situation	What KDIGO 2026 suggests	Grade
Hemodialysis with ferritin up to 500 and saturation up to 30	Start intravenous iron, proactively	2D
Outside hemodialysis, ferritin below 100 and saturation below 40	Start oral or intravenous iron	2D
Outside hemodialysis, ferritin from 100 to 300 and saturation below 25	Start oral or intravenous iron	2D
Ferritin above 700 or saturation of 40 or more	Stop routine iron	Practice point
Reversible causes corrected and persistent anemia	Stimulating agent as first line, ahead of HIF-PHI	2D
Dialysis with hemoglobin of 9 to 10 g/dl or less	Start stimulating agent	2D
Adult on treatment with stimulating agent	Keep hemoglobin below 11.5 g/dl (KDIGO Anemia Work Group, 2026)	1D
Sustained hyporesponse, with symptoms	A three to four month trial of HIF-PHI or transfusion	Practice point

Hyporesponse: when treatment does not work

The guideline calls initial hyporesponse the absence of a hemoglobin rise after the first month of treatment with the amount appropriate to weight. Acquired hyporesponse appears when, after a stable period, the patient starts needing two successive increases to maintain the target (KDIGO Anemia Work Group, 2026).

Look for the cause before increasing

The first step is to go back to the list of reversible causes: iron deficiency, inflammation, infection, occult bleeding, hyperparathyroidism, inadequate dialysis and poor adherence. KDIGO advises against repeated increases beyond twice the starting amount, because high amounts are associated with more cardiovascular events in the trials.

A trial with HIF-PHI

If the cause does not appear and hyporesponse persists with symptoms or transfusion risk, the guideline flowchart suggests a three- to four-month trial with HIF-PHI, stopped if there is no response (practice points 3.7.2 to 3.7.4). Those with active cancer, a recent cardiovascular event or recent thrombosis should stay out of this option. When pure red cell aplasia linked to the stimulating agent is suspected, the approach is to stop the agent, transfuse if necessary and discuss with the hematologist.

Similar reasoning appears with other drugs that affect hemoglobin, such as sotatercept in pulmonary hypertension, where the rapid rise also calls for delaying the next dose.

Transfusion: symptoms, transplant and what to avoid

The transfusion chapter is short and direct. KDIGO asks that transfusion be part of a complete strategy, decided with the patient (practice point 4.1), and based on the symptoms and signs of anemia, not on a fixed hemoglobin number (practice point 4.4) (KDIGO Anemia Work Group, 2026).

The transplant candidate

For those who can receive a kidney, the guideline asks to avoid transfusions whenever possible, because of the risk of alloimmunization (practice point 4.2). Antibodies against human leukocyte antigens formed after a transfusion reduce the chance of finding a compatible donor and may favor antibody-mediated rejection after transplant (Li, 2026). The topic gains weight with the new frontiers of transplant, such as xenotransplant protocols in patients on dialysis.

When transfusion makes sense

Transfusion tends to be worth more than its risks when the stimulating agent or HIF-PHI does not work, as in hemoglobinopathies and bone marrow failure, or when these drugs may cause harm, as in those who have had cancer or a stroke (practice point 4.3). In acute anemia, transfusion comes in when rapid correction is needed, as in acute bleeding, unstable coronary disease or before surgery (practice point 4.5). Patients with kidney disease are also at higher risk of circulatory overload, and knowing how to tell TACO and TRALI apart is part of the care.

Sparing blood in the hospital

Table 11 of the guideline suggests simple measures to reduce transfusions: limit blood draws, prefer less invasive procedures, maintain iron and the stimulating agent during hospitalization when there is no contraindication and look at the hemoglobin trend instead of a single value. In disaster situations, when dialysis and drugs are lacking, anemia worsens along with potassium, and the text on dialysis when power and water are lacking shows how to prioritize. Potassium, by the way, deserves attention when HIF-PHI is used outside dialysis, and recognizing hyperkalemia on the ECG helps in any scenario. In heart failure with kidney disease, the finerenone potassium table is a good example of adjustment guided by testing.

Back to the office

The man in the opening case has moderate anemia, symptoms and iron-restricted erythropoiesis, with ferritin of 180 and saturation of 18. The first step is to replace iron and investigate bleeding, since the drop was rapid. If hemoglobin remains low after iron is corrected, the conversation with him about a stimulating agent, with a target below 11.5 g/dl, comes next (KDIGO Anemia Work Group, 2026). HIF-PHI remains an alternative if there is hyporesponse or a strong preference for the oral route, provided he is outside the risk groups.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code.

The limits on using the game are described on the Economy page of NEXO. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information on Curator and on Creators, and institutions can learn about the proposal on the partnerships page. Choosing the right ICD-10 code completes this training.

Frequently asked questions

What changed in the names for iron deficiency?

KDIGO 2026 now calls absolute deficiency systemic iron deficiency and functional deficiency iron-restricted erythropoiesis. The first indicates low stores; the second indicates iron trapped by inflammation, which does not reach the marrow.

Does a normal ferritin rule out iron deficiency in kidney disease?

Ferritin rises with inflammation, so a value within range can hide iron deficiency for the marrow. That is why the guideline combines ferritin and transferrin saturation and suggests iron replacement with ferritin up to 300 when saturation is below 25, outside hemodialysis.

Does the HIF-PHI pill replace erythropoietin injections?

The guideline suggests the injectable stimulating agent as first line and leaves HIF-PHI as an alternative, especially in hyporesponse. Studies show similar efficacy, but follow-up is still short for risks such as cancer and retinopathy.

What is the hemoglobin target in treatment?

In adults treated with a stimulating agent, the target is to keep hemoglobin below 11.5 g/dl (KDIGO Anemia Work Group, 2026). Within that ceiling, the ideal value is individual and depends on symptoms, quality of life and transfusion risk.

Is premedication needed before intravenous iron?

Premedication with a corticosteroid or antihistamine is no longer routine, nor is a test dose. What matters is giving it where the team can treat a hypersensitivity reaction.

When should someone with chronic kidney disease receive a transfusion?

The decision follows the symptoms and signs of anemia, not a fixed hemoglobin number. Those who may receive a transplant should be spared transfusions whenever possible, because of the risk of forming antibodies.

Take-home messages

• Anemia of chronic kidney disease almost always has more than one cause, and iron comes first.
• The new names, systemic iron deficiency and iron-restricted erythropoiesis, explain why ferritin can mislead.
• Outside hemodialysis, iron is given with ferritin below 100 and saturation below 40, or ferritin up to 300 and saturation below 25.
• In hemodialysis, intravenous iron is proactive, with ferritin up to 500 and saturation up to 30.
• The injectable stimulating agent is first line; HIF-PHI is an alternative outside the risk groups.
• Hemoglobin below 11.5 g/dl in treated adults, with adjustments at most every four weeks (KDIGO Anemia Work Group, 2026).
• Transfusion based on symptoms, sparing the transplant candidate.

Milestone inventory

• 2012: KDIGO publishes the first guideline on anemia in chronic kidney disease, already with a conservative hemoglobin target.
• 2019: the PIVOTAL trial supports proactive intravenous iron in hemodialysis.
• 2021: the ASCEND and INNO2VATE programs compare HIF-PHI and stimulating agent in large populations.
• 2026: KDIGO updates the guideline, renames iron deficiency and places the stimulating agent ahead of HIF-PHI.

Play the case of the day on NEXO.

References

1. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease (CKD). Kidney Int. 2026;109(1S):S1-S99. DOI 10.1016/j.kint.2025.06.006. Read via the full PDF at kdigo.org.
2. Del Vecchio L, Cases A, Eisenga MF, et al. KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2026;41(8):1554-1572. PMID 41604211.
3. Spencer S, Skidmore M, McGing RM, Bhandari S. A systematic review investigating the safety and efficacy of intravenous iron in people with ND-CKD who are iron deficient but not anaemic. Clin Kidney J. 2026;19(7):sfag172. PMID 42441103.
4. Niu Y, Wang T, Zhan Y, et al. Efficacy and safety of prolyl hydroxylase inhibitors for anemia in chronic kidney disease: a network meta-analysis. Ren Fail. 2026;48(1):2616572. PMID 41633330.
5. Huang J, Wang Y, Zhang H, et al. Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on transfusion and intravenous iron use in chronic kidney disease anemia: a systematic review and meta-analysis. Front Pharmacol. 2026;17:1916346. PMID 42819330.
6. Birks P, Canney M, Djurdjev O, et al. Evaluation of Anemia Management in a Contemporary Population of Patients With Chronic Kidney Disease in Canada Since the Publication of Target Hemoglobin Trials: A Retrospective Observational Cohort Study. Can J Kidney Health Dis. 2026;13:20543581261468720. PMID 42466097.
7. Pribelszki P, Szász M, Tapolyai M. Proactive iron supplementation alone in patients on chronic hemodialysis is not sufficient. Ren Fail. 2026;48(1):2694788. PMID 42552952.
8. Dangre V, Rafiuddin M, Sriram K, et al. Time Course and Comparative Risk of Hypophosphatemia After Ferric Carboxymaltose versus Ferric Derisomaltose: A Systematic Review, Meta-analysis, and Clinical Cost Considerations. Hosp Pharm. 2026. PMID 42936098.
9. Li JSY. Short Course Immunosuppression to Prevent Transfusion-Related Human Leukocyte Antigen Sensitization in Kidney Transplant Candidates: Commentary. Kidney360. 2026;7(4):888-890. PMID 41032664.
10. Chertow GM, Agarwal R, Burke SK, et al. Comparing Vadadustat and Darbepoetin in Maintenance Dialysis with CKD-Related Anemia: A Win Statistics Analysis. J Am Soc Nephrol. 2026;37(6):1284-1286. PMID 41842948.
11. Kunitsu Y, Ikuta K, Hira D, et al. Risk of Heart Failure Hospitalization Associated With Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors Versus Erythropoiesis-Stimulating Agents: A Nationwide Claims-Based Cohort Study. Pharmacoepidemiol Drug Saf. 2026;35(9):e70453. PMID 42666150.
12. Dasgupta I, Meadowcroft AM, Bhatt PR, et al. Efficacy and safety of daprodustat in patients on peritoneal dialysis in the ASCEND-D trial. Nephrol Dial Transplant. 2025;40(7):1332-1341. PMID 39817409.