in pictures and a few words
What it is and why it matters
Vadadustat is a tablet for anaemia in adults with kidney disease who are on dialysis, when a machine cleans the blood.
- A tablet instead of hormone injections
- The body makes its own hormone that starts blood production
- No need to keep it cold
Why sick kidneys lead to anaemia
The kidneys are more than a filter. They make a hormone that tells the bone marrow to produce red blood cells.
- When the kidneys are ill, there is too little of this hormone
- Haemoglobin falls — that is how a blood test shows anaemia
- Hence weakness, breathlessness, effort is hard to bear
How it was treated before
For decades the missing hormone was given by injection. It works.
- But it needs injections, cold storage and careful dose adjustment
How the tablet works
Cells have their own oxygen sensor. The tablet makes the body behave as if the person had gone up into the mountains, though they went nowhere.
- In the mountains there is less oxygen, and the body itself steps up blood production
- The tablet does the same: the body makes its own hormone, not one from an injection
- Along the way, the body absorbs iron better
Tested in people on dialysis
In a large study in adults on dialysis, the tablet was compared with the standard hormone injection.
- It raised haemoglobin no worse than the injection
- For the heart and blood vessels — also no worse than the injection
Tested in people. Tested in people: a large study in adults on dialysis, compared with the standard injection.
Why only on dialysis
The tablet was approved where testing succeeded: for adults who have been on dialysis for at least three months.
- In people with sick kidneys not yet on dialysis, it raised haemoglobin just as well
- But it could not be shown to be just as safe for their heart and blood vessels
- This does not mean harm was proven: safety simply was not confirmed
No iron, nothing to build blood from
The tablet starts blood production, but the body builds blood from iron. If iron stores are empty, haemoglobin will not rise.
- Before and during treatment the doctor checks iron stores with blood tests
- Iron is prescribed based on the results — sometimes into a vein
- Iron tablets are taken no sooner than an hour after vadadustat
What haemoglobin is the goal
In kidney disease, haemoglobin is not raised to the level of a healthy person.
- Raising it to a full normal level led to more heart and blood vessel problems
- This applies to all medicines that spur blood production
- Your own goal — more modest than normal — is set by the kidney doctor
Who should see a doctor first
This is a prescription medicine: a kidney doctor (nephrologist) prescribes it and also keeps an eye on blood and liver tests.
- Kidneys are ill but no dialysis yet — under the US approval, the tablet is not for you
- Iron stores not refilled — iron first, then the tablet
- Blood pressure is high and treatment does not bring it down — this tablet is not allowed
Important. Do not swap injections for tablets on your own. The nephrologist decides: if the injections work well, the convenience of a tablet is not enough.
In one sentence
The tablet helps the body of a person on dialysis make its own blood hormone and raises haemoglobin no worse than an injection; iron and blood tests are still needed, and a kidney doctor prescribes it.
Key points
Vadadustat (brand name Vafseo) is a tablet for anaemia of chronic kidney disease that makes the body produce its own erythropoietin; the FDA approved it in March 2024 for adults on dialysis for at least three months.
| Situation | How it helps | What human studies showed |
|---|---|---|
| Anaemia in adults on dialysis for at least three months | raises haemoglobin: the body produces its own erythropoietin instead of receiving the finished hormone by injection | INNO2VATE (NEJM, 2021), 3,923 patients on dialysis: no worse than the standard injection, darbepoetin alfa, on both haemoglobin and cardiovascular events — 18.2% versus 19.3%, hazard ratio 0.96 (95% CI 0.83–1.11) [1] |
| Convenience on dialysis | a tablet instead of injections; no cold chain needed for storage | — |
| Iron metabolism | alongside erythropoietin, the tuning of iron metabolism switches on | — |
How it helps
Why haemoglobin falls in kidney disease
The kidneys are not only a filter. They produce erythropoietin, the hormone that tells the bone marrow to make red cells. As the kidneys fail the instruction stops arriving, and anaemia follows: fatigue, breathlessness, poor exercise tolerance.
For decades the answer was direct — inject the missing hormone. It works, but it requires injections, cold storage and careful dose titration.
How vadadustat works
The body has a built-in oxygen sensor: the HIF factor. When oxygen is plentiful a dedicated enzyme continuously degrades it. When oxygen is scarce — at altitude, for instance — the enzyme slows, HIF accumulates and switches on a programme: more erythropoietin, better iron handling, more active blood formation.
Vadadustat blocks that enzyme. The body behaves as if it had gone up a mountain, though the person has gone nowhere. From there it is the patient's own physiology doing the work, not an externally supplied hormone.
An important consequence: not only erythropoietin production switches on but the accompanying tuning of iron metabolism — the mechanism sits closer to the natural one than an injection of the finished hormone does.
What the trials showed
The development programme was built honestly: the same molecule was tested in two large trials — dialysis patients separately, pre-dialysis patients separately. In both cases the comparator was darbepoetin alfa, the standard injection, not placebo.
| INNO2VATE (dialysis) | PRO2TECT (non-dialysis) | |
|---|---|---|
| Patients | 3,923 | 3,476 |
| Comparator | Darbepoetin alfa | Darbepoetin alfa |
| Haemoglobin: non-inferior | Yes | Yes |
| Cardiovascular safety: non-inferior | Yes (HR 0.96) | No (HR 1.17, margin 1.25) |
| Regulatory outcome | Indication granted | No indication |
Why the indication is dialysis only
A regulator approves where the evidence held. Hence the unusually narrow wording of the indication: dialysis for at least three months. Not kidney disease, not anaemia in CKD — precisely the population in which the positive trial was run.
Where it sits among its relatives
| Drug | United States | Elsewhere |
|---|---|---|
| Vadadustat (Vafseo) | Approved, dialysis only | Approved in Japan, EU |
| Daprodustat (Jesduvroq) | Approved, dialysis only | Approved in Japan |
| Roxadustat (Evrenzo) | FDA refused | Approved in Japan, China, EU |
The pattern is visible: the US regulator accepted the class, but admitted only those molecules and those populations where the cardiovascular safety data were convincing. The class mechanism and the roxadustat story are covered in a separate guide.
How to take it
| Parameter | Detail |
|---|---|
| Formulation | Tablets |
| Who | Adults on dialysis ≥ 3 months |
| Storage | Ordinary; no cold chain |
| Monitoring | Haemoglobin, ferritin, transferrin saturation, liver tests |
| Iron | Usually required — stimulation without raw material is pointless |
| Timing | At least 1 hour before oral iron products, including iron-containing phosphate binders [4] |
Who should see a doctor first
Vadadustat is a prescription drug started by a nephrologist; switching from injections to tablets is also the nephrologist's decision.
A separate word on the goal of treatment: haemoglobin in kidney disease is not pushed to the level of a healthy person. Attempts at full normalisation produced more cardiovascular events in earlier trials, and that is a property of the entire class of agents stimulating blood formation. The target range is deliberately modest, and the nephrologist sets it.
The FDA label carries a boxed warning: an increased risk of death, myocardial infarction, stroke, venous thromboembolism and thrombosis of vascular access. That is why the lowest dose sufficient to reduce the need for red blood cell transfusions is used. Liver tests (ALT, AST, bilirubin) are checked before treatment starts, monthly for the first 6 months and then as clinically indicated [4].
Who it is not for
▸Patients with kidney disease not yet on dialysis: in the PRO2TECT trial a higher risk of cardiovascular events could not be ruled out in them (hazard ratio 1.17; 95% CI 1.01–1.36), so under the current US indication the drug is not prescribed to them [2]. ▸People with uncontrolled blood pressure — the label lists this as a contraindication [4]. ▸Anyone whose iron stores are not replenished: iron first, stimulation second. ▸Anyone expecting a normal haemoglobin: the goal of therapy is different and deliberately more modest.
Bottom line
▸Mechanism: mimicking oxygen shortage switches on the body's own erythropoietin production instead of injecting the hormone. ▸Dialysis patients: equivalent to the standard injection on both haemoglobin and cardiovascular events. ▸The shape of the approval mirrors the shape of the evidence: the indication is dialysis, where the data held. ▸Iron is mandatory — otherwise there is nothing to stimulate.
Treatment can be discussed at a consultation; the drug can be ordered here.
References
1. Eckardt KU, et al. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021;384(17):1601–1612. PMID 33913638
2. Chertow GM, et al. Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD. N Engl J Med. 2021;384(17):1589–1600. PMID 33913637
3. Sarnak MJ, et al. Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrol Dial Transplant. 2023;38(10):2358–2367. PMID 37096396
4. VAFSEO (vadadustat) — US Prescribing Information, Akebia Therapeutics.
Caveats
- Equivalent, not better. In the dialysis population the drug is equivalent to injections; it cannot be said to be safer than them.
- Patients not on dialysis. In PRO2TECT haemoglobin rose just as well, but the hazard ratio for cardiovascular events was 1.17 (95% CI 1.01–1.36): the upper bound exceeds the pre-specified margin of 1.25 [2]. This means a higher risk could not be ruled out — not that harm was proven. In such a situation the regulator acts conservatively; use before dialysis was not supported by the trial.
- The class. Roxadustat, daprodustat and vadadustat have different trial results and different regulatory fates: the mechanism is shared, but conclusions do not transfer from one to another. The FDA refused approval of roxadustat over safety questions.
- Long-term data beyond the trial horizons are limited.
For information only. Vadadustat is a prescription drug: prescribing and the treatment schedule are decided by a nephrologist.
Key facts
- Vadadustat (brand name Vafseo, Akebia/Otsuka) is an oral treatment for anaemia of chronic kidney disease from the class of HIF prolyl hydroxylase inhibitors: the drug mimics oxygen shortage, so the kidneys and liver start producing the body's own erythropoietin instead of it being injected from outside.
- The FDA approved it in March 2024 with a narrow indication: adults on dialysis for at least three months — exactly the population where the evidence held; in patients not on dialysis cardiovascular safety could not be confirmed.
- INNO2VATE (NEJM, 2021): 3,923 dialysis patients; on haemoglobin vadadustat was no worse than darbepoetin alfa, and a major cardiovascular event occurred in 18.2% on vadadustat versus 19.3% on darbepoetin alfa (hazard ratio 0.96; 95% CI 0.83–1.11) — the non-inferiority criterion was met.
- For a dialysis patient the practical gain is a tablet instead of injections, with no cold chain required for storage.
- The drug is prescription-only, started by a nephrologist, and requires monitoring of haemoglobin and iron stores — stimulating red cell production without iron is pointless.
