What is the recommended dosage of desidustat for adult patients with chronic kidney disease‑related anemia (both dialysis‑dependent and non‑dialysis)?

Desidustat Dosing for CKD-Related Anemia

For adult patients with chronic kidney disease-related anemia, initiate desidustat at 100 mg orally three times weekly, with dose adjustments every 4 weeks based on hemoglobin response to maintain a target of 10-12 g/dL. 1

Initial Dosing

• Start at 100 mg orally three times weekly for ESA-naïve patients with CKD stage 3-5 and baseline hemoglobin 7-11 g/dL 1, 2
• This lower starting dose applies to both dialysis-dependent and non-dialysis patients 1
• Administer at any time of day, with or without food 3

Dose Titration Protocol

• Adjust dose stepwise every 4 weeks according to current hemoglobin level and rate of change 1, 2
• Target hemoglobin range: 10-12 g/dL 1, 2, 4
• Temporarily discontinue if hemoglobin exceeds 12-13 g/dL 1, 2
• Resume at a reduced dose (one-third to one-half lower) once hemoglobin falls back into target range 1

Monitoring Requirements

Hemoglobin Monitoring

• Every 4 weeks during titration phase to assess response and guide dose adjustments 1, 2
• Every 3 months for non-dialysis patients on stable maintenance therapy 2
• Monthly for dialysis-dependent patients on maintenance therapy 2
• Increase frequency after dose changes, bleeding events, or inadequate response 2

Iron Status Monitoring

• Measure transferrin saturation (TSAT) and ferritin at least every 3 months during desidustat therapy 2, 4
• More frequent monitoring during initiation, dose escalation, or after bleeding 2
• Initiate iron supplementation first if TSAT ≤30% and ferritin ≤500 ng/mL before starting desidustat 2

Efficacy Data

The DREAM-ND phase 3 trial demonstrated that desidustat 100 mg three times weekly increased hemoglobin by 1.95 g/dL compared to 1.83 g/dL with darbepoetin, meeting non-inferiority criteria 1, 3. The responder rate (≥1 g/dL increase) was significantly higher with desidustat at 77.78% versus 68.48% with darbepoetin 3.

Absolute Contraindications

Do not use desidustat in:

• Active or recent malignancy undergoing curative treatment (theoretical HIF-mediated tumor promotion) 1, 2
• Polycystic kidney disease (preclinical data suggest HIF activation may accelerate cyst expansion) 1, 2
• Pediatric patients under 18 years (excluded from all phase 3 trials; no safety/efficacy data) 1, 2

Populations Requiring Caution

• Kidney transplant recipients: Limited data on interaction with immunosuppression and potential graft rejection risk 1, 2
• History of stroke: Increased vascular risk concerns 2
• Prior malignancy: Use with great caution even if not actively treated 2
• Marked systemic inflammation: Patients with elevated C-reactive protein showed only modest hemoglobin responses in trials 1

Critical Safety Warnings

Never exceed hemoglobin of 13 g/dL. Large trials consistently demonstrate that intentionally raising hemoglobin above this threshold increases cardiovascular events, stroke, and mortality 2, 4. This applies to all anemia therapies in CKD, not just desidustat.

Never combine desidustat with erythropoietin or other ESAs. This creates additive erythropoietic stimulation with substantially increased risk of exceeding safe hemoglobin targets and associated cardiovascular complications 4.

Practical Advantages

The oral route eliminates injection-related pain and improves convenience compared to injectable ESAs, particularly beneficial for non-dialysis and peritoneal dialysis patients 1, 2. Desidustat also enhances enteric iron absorption through hepcidin reduction, potentially beneficial in functional iron deficiency states 1.

Cardiovascular Safety Caveat

Unlike daprodustat, vadadustat, and roxadustat, desidustat lacks large cardiovascular outcomes trials with extensive endpoint data 1, 2. Exercise caution when prescribing to patients with cardiovascular disease history due to this limited long-term safety profile 1.