What is the recommended dosing, titration, monitoring schedule, safety precautions, and alternative therapy for desidustat in an adult with chronic kidney disease stage 3‑5 and anemia (baseline hemoglobin 7–11 g/dL)?

Desidustat for CKD Stage 3-5 Anemia: Dosing and Management

Starting Dose and Titration

Initiate desidustat at 100 mg orally three times weekly (TIW) for ESA-naïve patients with CKD stage 3-5 and baseline hemoglobin 7-11 g/dL, with dose adjustments every 4 weeks based on hemoglobin response to maintain target 10-12 g/dL. 1, 2

Dose Adjustment Protocol

• Start lower for ESA-naïve patients compared to those transitioning from ESAs, using the 100 mg TIW starting dose 3, 1
• Adjust dose in stepwise fashion every 4 weeks based on current hemoglobin level and rate of change 3, 2
• Temporarily discontinue if hemoglobin exceeds 12-13 g/dL, following protocols established in phase 3 trials 3, 1
• Consider discontinuation if hemoglobin targets are not achieved despite dose escalation 2

The DREAM-ND trial demonstrated mean hemoglobin increase of 1.95 g/dL with desidustat 100 mg TIW versus 1.83 g/dL with darbepoetin, meeting non-inferiority criteria 3, 4. Responder rates (≥1 g/dL increase) reached 77.78% with desidustat 4.

Monitoring Schedule

Hemoglobin Monitoring

• Every 4 weeks during titration phase to assess response and guide dose adjustments 1
• Maintain target 10-12 g/dL throughout treatment, consistent with ESA guidelines 1, 2
• Never target hemoglobin >12 g/dL due to increased cardiovascular events, stroke, and mortality demonstrated in multiple large trials 5

Iron Status Monitoring

• Monitor TSAT and ferritin at least every 3 months during desidustat treatment 5
• Desidustat reduces hepcidin levels, potentially enhancing enteric iron absorption and utilization 1, 4

Additional Safety Monitoring

• Evaluate for drug-drug interactions when used with other oral medications, as HIF-PHIs carry risk for interactions 3, 2
• Monitor for sepsis/septic shock signals and central hypothyroidism, though the latter has primarily been reported with roxadustat, not desidustat 1

Absolute Contraindications

Do not use desidustat in the following populations:

• Active or recent malignancy where cure is anticipated with primary/adjuvant chemotherapy 1, 2
• Polycystic kidney disease due to theoretical concerns about HIF activation enhancing cyst expansion 2
• Pediatric patients (under 18 years), as they were excluded from all phase 3 trials 3, 2
• Kidney transplant recipients due to limited data and potential effects on immune cell function 2

Safety Precautions

Cardiovascular Considerations

• Exercise caution in patients with cardiovascular disease history due to absence of large cardiovascular outcomes trials comparable to daprodustat, vadadustat, and roxadustat 1
• The oral route avoids high peak serum EPO concentrations seen with injectable ESAs, potentially reducing cardiovascular risks 2
• Long-term cardiovascular safety data remain more limited compared to other HIF-PHIs 2

Common Pitfalls to Avoid

• Never combine desidustat with ESAs (including epoetin or darbepoetin), as additive erythropoietic stimulation substantially increases risk of exceeding safe hemoglobin targets 5
• Do not use in ESA-hyporesponsive patients without evidence, as data supporting HIF-PHI efficacy in this population are limited 3
• Avoid in highly inflamed patients, as trial participants with elevated C-reactive protein had only slightly elevated levels 3

Alternative Therapy Options

When to Use ESAs Instead

• Initiate ESAs only after:
  • Iron stores corrected (TSAT ≤30%, ferritin ≤500 ng/mL addressed) 5
  • Other reversible causes of anemia treated 5
  • Hemoglobin remains <10 g/dL 5

Practical Advantages of Desidustat Over ESAs

• Oral administration eliminates injection-related pain and improves convenience, particularly beneficial for non-dialysis and peritoneal dialysis patients 1, 2
• Avoids subcutaneous injection burden that causes pain, especially important in pediatric populations (though desidustat itself is contraindicated in children) 3
• May be more effective in functional iron deficiency through hepcidin reduction and enhanced iron utilization 1

Clinical Context

Desidustat received first approval in India (March 2022) for anemia in adults with CKD, both dialysis-dependent and non-dialysis-dependent 6. The American Kidney Foundation recommends considering desidustat as a treatment option given its non-inferiority to ESAs 1. However, the European Renal Association emphasizes caution in cardiovascular disease patients due to limited long-term safety data 1.