Anaemia of chronic disease and of kidney disease

• Anaemia of chronic disease (ACD, now also called anaemia of inflammation) is not a shortage of iron in the body: it is a shortage of iron available to the marrow. Inflammation traps iron inside macrophages and blocks its absorption, while pro-inflammatory cytokines suppress red cell production and blunt the response to erythropoietin.
• The signature is a normocytic or mildly microcytic anaemia with low serum iron and transferrin saturation, but normal or raised ferritin. The soluble transferrin receptor is normal and the ratio of soluble transferrin receptor to log ferritin is low (under 1), which separates it from iron deficiency anaemia, where ferritin is low and the ratio is high (over 2).^[1]
• Severity is usually mild to moderate, with haemoglobin around 8 to 9.5 g/dL and rarely below 6 g/dL.^[1] Always look for the underlying cause and exclude absolute iron deficiency, because the treatments differ.
• Anaemia in chronic kidney disease (CKD) overlaps with ACD but adds a specific problem: failing kidneys make too little erythropoietin, and iron handling is disrupted. Renal anaemia usually appears once estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m² and becomes more definite below 30.^{[5] [1][2]}
• Thresholds differ between guidelines. The KDIGO 2026 guideline, as cited via the ERBP commentary, starts ESAs when haemoglobin is 9 to 10 g/dL in dialysis patients, keeps haemoglobin below 11.5 g/dL, and redefines iron deficiency in CKD as "systemic iron deficiency" (low ferritin with low transferrin saturation) and "iron-restricted erythropoiesis" (normal or raised ferritin with low transferrin saturation).^[2]

By the end of this page you should be able to:

1. Explain why inflammation produces anaemia, through hepcidin, iron restriction, cytokines and a blunted erythropoietin response.
2. Recognise the laboratory pattern of anaemia of chronic disease and separate it from iron deficiency anaemia and from haemolysis.
3. Explain why chronic kidney disease causes anaemia, including the role of erythropoietin and iron.
4. Investigate renal anaemia using the tests each guideline suggests, with their cut-offs.
5. Manage renal anaemia step by step: iron (route, targets, safety), ESAs (when to start, targets, dose adjustment, resistance), HIF-prolyl hydroxylase inhibitors, transfusion.
6. Compare what different guidelines say where they disagree, and adapt care to low-resource settings.

ACD is the most common cause of anaemia in admitted patients and the second most common cause overall, after iron deficiency anaemia.^[1] The umbrella term covers chronic infections (including HIV), malignancy, autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease), chronic rejection after organ transplantation, and chronic kidney disease.^[1]

CKD has its own form of anaemia, sometimes called renal anaemia. It is included here because the mechanisms overlap (inflammation, hepcidin, iron restriction) and because many patients with CKD have both.

Classifications that help practice. Anaemias are usually first sorted by mean cell volume into microcytic, normocytic and macrocytic groups. ACD is usually normocytic at first and becomes microcytic later, once iron restriction becomes prominent.^[3] In CKD, the anaemia is typically normocytic and normochromic.^[2]

A more useful distinction for treatment is absolute versus functional iron deficiency.^[1]

• Absolute (systemic) iron deficiency means the iron stores themselves are depleted. Serum ferritin is low.
• Functional (or iron-restricted) deficiency means iron is present in stores but is not released for red cell production, usually because raised hepcidin blocks its export. This is what happens in ACD and in many patients with CKD.

These two produce the same low serum iron and low transferrin saturation, but only absolute deficiency responds reliably to oral iron on its own.

Anaemia of chronic disease. Because ACD is often mixed with iron deficiency, its exact prevalence is hard to pin down. The table below gives estimated prevalences from the in-depth review by Madu and Ughasoro.^[1]

Anaemia in CKD. Anaemia is roughly twice as common in people with CKD as in the general population (15.4% versus 7.6%), and prevalence rises with stage: from 8.4% in stage 1 to 53.4% in stage 5 in NHANES data reported by Portolés and colleagues.^[5] Prevalence rises more sharply as eGFR falls below 30 mL/min/1.73 m².^[2]

Real-world management is imperfect. In the 25th UK Renal Registry report (2021 data), 53.8% of people receiving kidney replacement therapy had haemoglobin below 100 g/L and over 20% of dialysis patients had haemoglobin below 90 g/L; median haemoglobin was 107 g/L for transplant recipients, 106 g/L for peritoneal dialysis and 94 g/L for haemodialysis.^[4] Anaemia usually starts in CKD stage 3, and one nondialysis cohort developed anaemia at 11% per year in year one, rising to 26% by year three.^[5]

ACD appears when an illness generates sustained immune activation. Risk is driven more by the activity of the underlying illness than by its name.

CKD causes anaemia through several routes at once:

1. Relative failure of erythropoietin production as functioning kidney mass falls.^[5]
2. Absolute iron deficiency from blood loss, especially on haemodialysis.
3. Functional iron restriction from inflammation and raised hepcidin.
4. Shortened red cell survival and uraemia suppressing marrow response.
5. Nutritional deficiency (folate or vitamin B12) and haemolysis, which must always be sought because they are treatable.
6. Drugs and other causes: bleeding from gastrointestinal lesions is common in CKD and should be investigated when iron deficiency is present.

Extra risk in CKD comes from diabetes, older age and frailty, polypharmacy and the dialysis procedure.

Most of the body's iron is found in haemoglobin. Only a small amount is lost each day, so absorption from the duodenum must be tightly controlled. Dietary iron is absorbed through duodenal enterocytes using a divalent metal transporter (DMT-1) and exported into the blood through the only iron exporter, ferroportin. In the blood, iron binds transferrin for delivery to the marrow. Macrophages recycle iron from old red cells, and hepatocytes store it as ferritin. The master regulator is hepcidin, a 25-amino acid peptide made in the liver. ^[1]

Hepcidin is a hairpin-shaped molecule secreted by liver cells. It decreases iron absorption from the duodenum and iron release from macrophages by binding ferroportin and causing it to be internalised and broken down.^[1] In effect, hepcidin closes the gate that lets iron leave stores.

Hepcidin synthesis rises with iron overload and inflammation, and falls with iron deficiency, anaemia and hypoxia. In ACD, bacterial lipopolysaccharides and interleukin-6 (IL-6) stimulate the liver to produce hepcidin.^[1] The result is a hypoferraemic environment: iron is locked inside macrophages and enterocytes, unavailable to erythroid precursors. This is the reticuloendothelial iron block. The body is essentially choosing to hide iron from invading microbes and tumour cells, but red cell production pays the price.

Hepcidin is also produced to some extent by activated neutrophils and macrophages. In CKD its clearance by the kidney falls as eGFR declines, so levels stay higher for longer.^[5]

Interleukin-6 is regarded as the most important cytokine in ACD. It inhibits erythropoiesis through several routes besides hepcidin: it downregulates expression of a key gene in late erythroid precursors, reducing haemoglobin synthesis, and it suppresses marrow directly. Tumour necrosis factor-alpha stimulates ferritin synthesis and phagocytosis of red cells while directly inhibiting erythropoiesis. Interferon-gamma increases iron uptake into cells, reduces transferrin receptor expression, induces nitric oxide production and, in extreme cases, drives apoptosis of red cell precursors.^[1]

In ACD the bone marrow receives less signal and responds less well. Erythropoietin (EPO), produced mainly by the peritubular fibroblast-like cells of the kidney, may be low or inappropriately normal for the degree of anaemia. A "relative deficiency" is common when erythropoietin levels are measured. In a quarter of patients with end-stage renal disease the response to exogenous erythropoietin is blunted, requiring higher doses.^[1]

Nitric oxide, oxygen free radicals and inflammatory proteins contribute to this blunting. Vitamin D signalling has been associated with improved erythropoietin responsiveness in some patients, but the evidence is limited.

Iron restriction, inflammatory cytokines and reactive oxygen species shorten red cell lifespan. In malignancy, physical invasion of the marrow adds a further mechanism, but inflammation rather than infiltration is the dominant driver in most cancer patients.

In CKD, absolute erythropoietin deficiency starts early and becomes more severe once eGFR falls below 30 mL/min/1.73 m². The mechanisms are: ^[5]

• Reduced erythropoietin synthesis and disrupted renal oxygen sensing: the kidney adapts to reduced blood flow by consuming less oxygen, so the hypoxia-inducible factor signal does not fire and erythropoietin gene transcription stays low.^[5]
• Iron deficiency, absolute (blood loss on dialysis) and functional (hepcidin).
• Systemic inflammation raising hepcidin.
• Uraemic toxins inhibiting the marrow response to erythropoietin.
• Shortened red cell lifespan.
• Losses of folate and vitamin B12 in dialysate.

The anaemia is usually mild to moderate (haemoglobin around 8 to 9.5 g/dL) and develops in someone already known to be chronically ill. Symptoms are often those of the underlying illness plus fatigue, reduced exercise tolerance and pallor. Severe anaemia (below 6 g/dL) should prompt a search for additional causes.^[1] The reticulocyte count is low. The blood film is initially normochromic and normocytic, later becoming hypochromic and microcytic as iron restriction develops.

Early on there may be no symptoms. From NICE, symptoms attributable to anaemia include tiredness, shortness of breath, lethargy and palpitations.^[3] As haemoglobin falls, left ventricular work increases and quality of life drops. Anaemia in CKD is associated with higher morbidity and mortality and higher cost.^[5]

Two questions help: is this anaemia caused by inflammation, by iron deficiency, or by both? And if the patient has CKD, is the anaemia explained by the kidney, or is something else going on?

The classic separator between ACD and iron deficiency anaemia is the pattern of iron studies.^[1]

Key points from this table:

• Ferritin is an acute-phase protein, so it rises in inflammation. A "normal" ferritin in someone with active inflammation does not exclude iron deficiency.
• Transferrin falls or stays normal in ACD but rises in iron deficiency.
• The sTfR/log ferritin ratio (under 1 in ACD, over 2 in iron deficiency) is the best separator among simple tests when it is available, and is less affected by inflammation.

Haemolysis, marrow failure, bleeding and mixed nutritional deficiency should also be ruled out. In CKD, other causes (myeloma, gastrointestinal cancer, haemolysis) must be considered, since anaemia is a diagnosis of exclusion.

1. Full blood count and blood film morphology, including MCV.
2. Reticulocyte count (low in ACD and in iron deficiency; raised in haemolysis or bleeding).
3. Iron studies: serum iron, transferrin (or total iron-binding capacity), transferrin saturation, ferritin. Add sTfR if available.
4. Markers of inflammation such as C-reactive protein.
5. Tests for the underlying disease and its activity.
6. Consider vitamin B12 and folate, renal and liver function, stool and urine testing, and haemolysis screens when appropriate.

Some degree of absolute iron deficiency is common in ACD, especially in inflammatory bowel disease and CKD. When iron deficiency is proven or the patient is not responding to erythropoietin, iron is appropriate.^[1]

The definitions of iron deficiency differ by guideline, and the cut-offs differ between dialysis and non-dialysis patients.

NICE (NG203) recommends, every 3 months (1 to 3 months on haemodialysis), testing to diagnose iron deficiency and predict response to iron: ^[3]

• percentage of hypochromic red cells (%HRC), more than 6%, if blood can be processed within 6 hours;
• if not, reticulocyte haemoglobin content (CHr), less than 29 pg (or equivalent);
• when those tests are not available, or the patient has thalassaemia or its trait, pair a transferrin saturation under 20% with a serum ferritin under 100 micrograms/L.^[3]

NICE also says not to request transferrin saturation or ferritin alone, and not to routinely measure erythropoietin levels.^[3]

UK Kidney Association (2025) largely agreed with NICE and added practical repletion criteria. Repletion is usually defined as %HRC under 6%, CHr above 31 pg, and ferritin with transferrin saturation above 100 micrograms/L and above 20% in non-dialysis or peritoneal dialysis patients, and above 200 micrograms/L in people on haemodialysis.^[4] CHr below 31 pg indicates iron depletion. Iron should be considered when ferritin is below 500 micrograms/L and/or transferrin saturation is below 30%.^{[4] [3]}

KDIGO 2026, as summarised by the ERBP commentary, redefines iron deficiency in CKD as:

• Systemic (absolute) iron deficiency: transferrin saturation under 20% with ferritin under 100 ng/mL (under 200 ng/mL on haemodialysis). ^[4]
• Iron-restricted erythropoiesis (functional deficiency): transferrin saturation under 20% with ferritin in the 100 to 200 ng/mL range.

This is a change of name rather than of biology. KDIGO 2026 also recommends checking a full blood count, reticulocyte count, ferritin and transferrin saturation at diagnosis, and suggests further evaluation if the cause is not clear (peripheral smear, vitamin B12 and folate, liver enzymes, haptoglobin, faecal occult blood, thyroid-stimulating hormone, lactate dehydrogenase, C-reactive protein, and, where indicated, protein electrophoresis, free light chains and urinary Bence-Jones protein). Severe iron deficiency should prompt evaluation for blood loss, with urology, gastroenterology or gynaecology referral.^[2]

Most guidelines agree that absolute iron deficiency must be corrected before starting ESA or HIF-PHI therapy, or the drugs will fail and iron restriction worsens.^[3][4] Transferrin saturation and ferritin should be re-checked during treatment.

There is no separate staging system for ACD; the diagnosis rests on the underlying illness plus the iron-study pattern. For CKD, the CKD stage (G1 to G5, based on eGFR and albuminuria) provides context: anaemia becomes common below an eGFR of 60, and more so below 30. NICE suggests considering investigation when haemoglobin falls to 110 g/L or below, or when the person has symptoms attributable to anaemia.^[3] UKKA uses the same 110 g/L threshold (105 g/L in children under 2 years) for investigating the cause, irrespective of CKD stage.^[4]

For CKD specifically, erythropoietin levels should not be routinely measured; they are reserved for selected cases, because the result rarely changes management.^[3][4]

The goals are to improve oxygen-carrying capacity, relieve symptoms and treat the underlying cause. The steps are:

1. Treat or control the underlying disease. Activity of inflammation is the driver.
2. Exclude and treat absolute iron deficiency. Oral iron is reasonable when absorption is intact; parenteral iron is reserved for proven malabsorption or failure. Madu and Ughasoro note that giving excess iron can support microbial and tumour growth and suppress immunity, so iron must be justified.^[1]
3. Consider an erythropoiesis-stimulating agent (ESA) when anaemia is symptomatic and the underlying disease cannot be controlled quickly, particularly in chemotherapy-associated anaemia, CKD and HIV infection. ESAs in ACD are used with iron, with a haemoglobin target between 11 and 12 g/dL.^[1]
4. Transfuse when haemoglobin is severely low (below about 6.5 g/dL) with cardiac decompensation or when rapid correction is clinically required.^[1] Long-term transfusion is avoided because of iron overload and alloimmunisation, especially if transplantation is possible.
5. Targeting cytokines or hepcidin directly (anti-IL-6, anti-hepcidin antibodies, other agents) remains investigational.

Iron is the first treatment to get right, because ESAs and HIF-PHI drugs both increase iron demand. The route depends on the situation.

• Oral iron is reasonable for non-dialysis CKD, particularly mild iron deficiency, when the person can tolerate it.
• Intravenous iron is preferred for most people on haemodialysis; for non-dialysis CKD with more severe deficiency, poor tolerance, or need to start ESAs; and should be considered for peritoneal dialysis patients starting ESAs.^[4]
• High-dose, low-frequency intravenous iron is convenient for non-dialysis and peritoneal dialysis patients. IV iron must be given only where resuscitation is available, since severe reactions occur. Iron should be temporarily suspended during active infection.^[4]

Initiation thresholds differ by guideline. The ERBP commentary table comparing KDIGO 2012, ERBP 2013 and KDIGO 2026 gives these values:^[2]

• KDIGO 2026, NDD-CKD: suggest starting iron when ferritin is under 100 ng/mL and transferrin saturation under 40%, or when ferritin is 100 to 299 ng/mL with transferrin saturation under 25%. ^[2]
• KDIGO 2026, haemodialysis: IV iron when transferrin saturation is 30% or below and ferritin 500 ng/mL or below; a proactive IV iron strategy is suggested (Practice Point 2.1, based on PIVOTAL: 400 mg iron sucrose monthly, withheld if ferritin reaches 700 ng/mL or transferrin saturation reaches 40%). ^[2]
• KDIGO 2026 upper limits: withhold routine iron if ferritin is 700 ng/mL or above or transferrin saturation is 40% or above. ^[2]

By contrast, NICE sets lower safety ceilings: ferritin should not rise above 800 micrograms/L on iron, with a dose review when ferritin reaches 500 micrograms/L, and ESAs should not be started in absolute iron deficiency without also correcting the iron deficiency.^[3] UKKA sets ferritin should not exceed 600 micrograms/L in non-dialysis patients treated with iron (review at 500), and proactive high-dose IV iron in haemodialysis at 600 mg in divided doses in the first month and 400 mg every month unless ferritin exceeds 700 micrograms/L or transferrin saturation exceeds 40%.^[4]

Both NICE and UKKA define repletion more conservatively (ferritin above 100 micrograms/L with transferrin saturation above 20% in non-dialysis patients, CHr above 31 pg).^[3][4] The KDIGO 2026 thresholds are more proactive, aiming to find and treat iron deficiency earlier. Guidelines differ here, and neither approach has been shown to improve long-term outcomes in all populations.

In haemodialysis every 1 to 3 months on IV iron, and in non-dialysis patients every 3 months, re-check iron studies.^[3][4]

Non-anaemic iron deficiency: UKKA recommends IV iron for people with CKD who have iron deficiency without anaemia and concomitant heart failure, to improve well-being and reduce heart failure admissions.^[4]

ESAs are recombinant erythropoietin (epoetin alpha/beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) and biosimilars. ESAs are suggested as the first-line pharmacological treatment for anaemia in CKD over HIF-prolyl hydroxylase inhibitors because of more established safety, although the recommendation is weak (2D).^[2]

When to start. KDIGO 2026 keeps the 2012 thresholds: initiate when haemoglobin falls to 9.0 to 10.0 g/dL in haemodialysis or peritoneal dialysis patients (2D), and for non-dialysis patients, including kidney transplant recipients and children, the decision should be individualised, taking into account symptoms, benefits of higher haemoglobin and risks of transfusion and therapy (2D).^[2] UKKA and the ERBP commentary argue that haemoglobin should not routinely be allowed to fall below 10 g/dL, and that earlier initiation may be justified for symptomatic patients, particularly with advanced CKD or likely transplant candidates.^[2][4] NICE focuses on having iron replete first and considering a trial of anaemia management, and notes that ESAs need not be given if comorbidity or prognosis would negate benefit.^[3]

Maintenance target. Here is a point of genuine disagreement between guidelines:

• KDIGO 2026 recommends maintaining haemoglobin below 11.5 g/dL to avoid stroke, cardiovascular events and thrombosis (1D).^[2]
• ERBP, UKKA and NICE’s older targets (from Portolés et al.) prefer 10 to 12 g/dL, individualised to risk and symptoms.^[4][5]

Rather than quoting one number as if it were settled, state the disagreement: aim for between 10 and 11.5, staying below 11.5, and individualise within that range. Whatever the target, avoid overshooting quickly: Hb rise should not exceed about 1 g/dL in two to four weeks (KDIGO) or 2 g/dL in four weeks (ERBP), to limit thrombotic risk. UKKA recommends dose adjustments when Hb is below 105 g/L or above 115 g/L in adults, to keep the population mean near 110 g/L with a range of 100 to 120 g/L.^[2][4]

Iron must be replete before and during ESA therapy. Absolute iron deficiency must be corrected first; during therapy, %HRC, CHr and transferrin saturation should be monitored so iron does not become the limiting factor.^[4]

Monitoring. Check haemoglobin every 2 to 4 weeks during ESA correction or after a dose change, and every 1 to 3 months once stable.^[4] ESA dose should be individualised from the starting haemoglobin, desired target, observed rate of rise and clinical circumstances; subcutaneous administration is preferred for non-dialysis patients to avoid venepuncture.^[4]

Resistance. Inadequate response ("resistance") to ESA therapy is defined as failure to reach the target haemoglobin despite subcutaneous epoetin above 300 IU/kg/week (450 IU/kg/week intravenously), or darbepoetin above 1.5 micrograms/kg/week, after investigating and treating other causes.^[4] Causes to seek: absolute or functional iron deficiency, inflammation, infection, occult bleeding, vitamin B12 or folate deficiency, secondary hyperparathyroidism, haemolysis, aluminium overload, malignancy. Strategies include optimising iron, treating the underlying cause, considering a HIF-PHI trial, or accepting a lower haemoglobin target on high ESA doses.^[4]

Caution and red flags. Use ESAs cautiously with a history of stroke or malignancy (particularly active malignancy with curative intent), uncontrolled hypertension, and during hospitalisation for acute stroke, vascular access thrombosis or thromboembolism, when treatment should be suspended and re-initiation individualised. ESA-induced pure red cell aplasia (PRCA) is rare: consider it when, after more than 8 weeks of ESA, there is a sudden haemoglobin fall of about 5 to 10 g/L per week with normal white cell and platelet counts, very low reticulocytes and high ferritin. All ESA therapy must be stopped, and immunosuppression considered if transfusion-dependent.^[4]

These oral drugs (roxadustat, daprodustat, vadadustat, molidustat, enarodustat and others) inhibit the prolyl hydroxylase domain enzymes, stabilising hypoxia-inducible factor, increasing endogenous erythropoietin production and improving iron availability (including by lowering hepcidin). They are an alternative when ESAs are hyporesponsive or impractical. They must be started after iron repletion.

Approvals vary by region, and this matters for safety as well as prescribing. Roxadustat is approved in Europe for both dialysis and non-dialysis CKD but is not approved in the USA; vadadustat and daprodustat are approved for dialysis patients in the USA and in Europe (vadadustat), with daprodustat withdrawn from the European market by the manufacturer. ESA (or HIF-PHI) treatment is guided by haemoglobin 10 to 12 g/dL targets, and NICE additionally recommends roxadustat for symptomatic anaemia in non-dialysis stage 3 to 5 CKD without iron deficiency, and vadadustat for dialysis patients, via their technology appraisals.^[2][3][4]

KDIGO 2026 suggests considering HIF-PHIs as a reasonable option in ESA hyporesponsiveness or intolerance, chronic inflammation with elevated CRP, needle-phobia or self-administration problems, and home or peritoneal dialysis, while advising avoidance in active malignancy, polycystic kidney disease, proliferative retinal disease, pulmonary arterial hypertension and pregnancy, and caution with prior cardiovascular or thrombotic events and drug interactions.^[2][4]

Monitoring during HIF-PHI therapy: measure haemoglobin every two weeks until target is achieved and stable, then every four weeks.^[4]

Transfusion should be avoided if possible when kidney transplantation is an option, to minimise allosensitisation. If essential (acute bleeding, haemolysis, severe sepsis), transfuse according to local transfusion policy rather than by ESA target, using single-unit transfusions where possible in stable non-bleeding patients.^[4] Madu and Ughasoro note earlier that severe anaemia (haemoglobin below 6.5 g/dL) with cardiac decompensation warrants transfusion.^[1]

• Cardiovascular: left ventricular hypertrophy and heart failure worsen with anaemia; severe dialysis anaemia doubles mortality relative to haemoglobin 10 to 11 g/dL.^[1]
• Transfusion risk, allosensitisation and iron overload.
• Iron toxicity and infection risk with excess stored iron.
• ESAs: hypertension, thrombosis, PRCA (rare), possible stroke and cardiovascular events at higher haemoglobin; cancer-related concerns.
• HIF-PHIs: variable safety by agent, thromboembolic and vascular-access events, seizures, infections, drug interactions.
• Reduced quality of life, exercise tolerance and cognitive function, and possibly faster CKD progression.

Correcting severe anaemia improves symptoms and reduces transfusion. Large trials (CHOIR, CREATE, TREAT) show that targeting normal or near-normal haemoglobin (13 to 15 g/dL) with ESAs does not reduce cardiovascular or renal events and may increase harm (stroke in TREAT). A clear benefit is seen when correcting below 10 g/dL. The haemoglobin target therefore sits between 10 and 12 g/dL for most patients, individualised to symptoms, comorbidity and preference.^[5]

• Screen for anaemia: at least annually in CKD stage 3, and at least twice a year in stages 4 to 5 not on replacement therapy.^[4]
• Investigate the cause before treating, including blood loss and nutritional deficiency.
• Prevent iron deficiency in dialysis with proactive iron, and minimise blood loss: avoid unnecessary venepuncture and retain blood in the circuit.
• Manage hyperparathyroidism and inflammation, which blunt ESA response.
• Optimise nutrition, transplantation evaluation and timely anaemia correction.

• Children: diagnostic thresholds use 105 g/L under age 2; haemoglobin targets on ESAs are 95 to 115 g/L under age 2 and 100 to 120 g/L at age 2 and above; target ferritin above 100 micrograms/L. Iron therapy decisions should be guided by the same CHr/%HRC principles.^[4]
• Pregnancy: parenteral iron from the second trimester may be used if benefits outweigh risks; ESAs are continued unless contraindicated by hypertension or thrombosis risk.^[4]
• Transplant recipients: manage anaemia like non-dialysis CKD; ESAs may continue post-transplant until endogenous erythropoietin is sufficient; continue HIF-PHIs as in non-dialysis CKD, although data are limited.^[4]
• Cancer patients: treat symptomatic anaemia when haemoglobin is below 100 g/L.^[4]
• Heart failure: correct iron deficiency with IV iron to improve function and reduce admissions even when anaemia is absent.^[4]
• Older, frail patients: weigh risks and benefits of invasive investigation and transfusion.

• A full blood count and ferritin plus transferrin saturation are the minimum workable set. Where %HRC/CHr is unavailable, use the combination of transferrin saturation (less than 20%) and ferritin (less than 100 micrograms/L).^[3][4]
• If laboratories are very limited, rely on MCV, red cell morphology, ferritin, and clinical evidence of inflammation and CKD stage. Avoid anchoring on a single ferritin in febrile or infected patients, because ferritin rises as an acute-phase reactant.
• Oral iron is affordable; intravenous iron requires resuscitation capacity. ESAs and HIF-PHIs are costly and many agents are not locally approved, so use them only where monitoring of haemoglobin and blood pressure is possible.
• Investigate blood loss (stool and urine) when iron deficiency is disproportionate.
• In haemodialysis settings without IV iron supply, oral iron has limited value; transfusion and ESAs become the pragmatic tools, but both carry risks of sensitisation and hypertension.

• Anaemia of chronic disease is functional iron restriction, not absolute deficiency: iron is present but trapped by high hepcidin.
• Hepcidin, a 25-amino acid liver peptide, degrades ferroportin and blocks iron absorption and release; IL-6 is the main stimulus.^[1]
• The typical picture: normocytic (later microcytic) anaemia, low serum iron and transferrin saturation, normal or raised ferritin, normal sTfR, low sTfR/log ferritin ratio (under 1).^[1]
• IL-6, TNF-alpha and IFN-gamma also suppress erythropoiesis and blunt erythropoietin response; a quarter of end-stage CKD patients show blunted response.^[1]
• Haemoglobin is usually 8 to 9.5 g/dL and rarely below 6 g/dL in ACD; severe anaemia demands another cause.^[1]
• CKD anaemia is driven by relative erythropoietin failure (worse below eGFR 30), iron deficiency, inflammation and marrow suppression.^[5]
• NICE (NG203): investigate at Hb 110 g/L or below or with symptoms; re-check iron studies 3-monthly using %HRC, CHr or TSAT + ferritin; no routine EPO assay; ferritin should not exceed 800 micrograms/L (review at 500).^[3]
• UKKA (2025): screen annually in CKD 3, twice-yearly in CKD 4 to 5; investigate at 110 g/L (105 under age 2); repletion %HRC under 6%, CHr above 31 pg, ferritin above 100 micrograms/L (non-dialysis) or above 200 (dialysis); do not exceed 600 micrograms/L non-dialysis; proactive HD iron 600 mg first month then 400 mg monthly unless ferritin above 700/TSAT above 40.^[4]
• KDIGO 2026: anaemia at Hb under 13 g/dL (men) and under 12 g/dL (women); redefine iron deficiency as systemic (TSAT under 20%, ferritin under 100/200) and iron-restricted erythropoiesis (TSAT under 20%, ferritin 100 to 200); initiate ESA at 9 to 10 g/dL on dialysis; individualise in non-dialysis; maintenance Hb below 11.5 g/dL; start ESA only after iron repletion.^[2]
• ESAs are first-line over HIF-PHIs, which remain an option for hyporesponsiveness or practical barriers; monitoring and approval differ by agent and region.^[2][4]
• ESA resistance: subcutaneous epoetin above 300 IU/kg/week (IV above 450) or darbepoetin above 1.5 micrograms/kg/week after work-up; aim to keep the population mean haemoglobin near 110 g/L, between 100 and 120 g/L.^[4]
• Avoid transfusion when transplant is possible; transfuse for acute bleeding or haemodynamic compromise.^[1][4]
• Targeting haemoglobin above 13 g/dL with ESAs increases harm; the therapeutic zone is roughly 10 to 11.5 g/dL.^[5]
• Treat the underlying disease first in ACD; iron helps only when absolute deficiency coexists; ESAs help when inflammation is persistent.

anaemia-approach-and-iron-deficiency, chronic kidney disease, haemolytic anaemias, aplastic anaemia, autoimmune haemolytic anaemia, sideroblastic and megaloblastic anaemia, anaemia in pregnancy, thrombocytopenia and bleeding disorders