What is the recommended dosing, monitoring, contraindications, and dose adjustments for Desidustat in an adult patient with chronic kidney disease and anemia (hemoglobin 7–11 g/dL)?

Desidustat for Anemia in CKD: Dosing, Monitoring, and Contraindications

Desidustat is an oral HIF-prolyl hydroxylase inhibitor approved for treating anemia in adult CKD patients (both dialysis-dependent and non-dialysis-dependent), with a starting dose of 100 mg three times weekly for ESA-naïve patients, targeting hemoglobin levels of 10-12 g/dL. 1, 2

Initial Dosing Strategy

• 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
• Lower starting doses are specifically recommended for ESA-naïve patients compared to those transitioning from other ESAs 1
• The DREAM-ND trial demonstrated a mean hemoglobin increase of 1.95 g/dL with this regimen versus 1.83 g/dL with darbepoetin, meeting non-inferiority criteria 2, 3
• In dialysis-dependent patients, desidustat showed a hemoglobin change of 0.95 g/dL versus 0.80 g/dL with epoetin alfa 4

Dose Titration and Adjustments

• Adjust dose stepwise every 4 weeks based on current hemoglobin level and rate of change 2
• Target hemoglobin range is 10-12 g/dL, consistent with KDIGO guidelines for ESAs 5, 1
• Temporarily discontinue desidustat if hemoglobin exceeds 12-13 g/dL, following protocols from phase 3 trials 1, 2
• Consider permanent discontinuation if hemoglobin targets are not achieved despite dose escalation 1
• Avoid repeated dose escalations beyond double the initial weight-based dose in hyporesponsive patients, similar to ESA management 5

Monitoring Requirements

Hemoglobin Monitoring

• Monitor hemoglobin every 4 weeks during dose titration 2
• For stable patients not on treatment: every 3 months for CKD 3-5ND and CKD 5PD; monthly for CKD 5HD 5
• For patients on desidustat: at least every 3 months during maintenance phase 5

Iron Status Monitoring

• Evaluate iron status (TSAT and ferritin) at least every 3 months during desidustat therapy 5, 6
• Monitor more frequently when initiating or increasing dose, with blood loss, or when iron stores may become depleted 5
• Ensure TSAT ≤30% and ferritin ≤500 ng/ml are addressed before initiating therapy 5, 6

Additional Monitoring

• Evaluate potential drug-drug interactions when co-administered with other oral medications 1, 2
• Monitor for HIF-PHI class-specific adverse effects including sepsis/septic shock signals and central hypothyroidism 2

Absolute Contraindications

Malignancy

• Do not use in patients with active malignancy, particularly when cure is the anticipated outcome with primary or adjuvant chemotherapy 1, 2
• Exercise great caution in patients with history of malignancy, similar to ESA guidelines 5

Polycystic Kidney Disease

• Avoid in polycystic kidney disease patients until adequate safety data emerge, as HIF activation may potentially enhance cyst expansion based on preclinical models 1, 2

Pediatric Patients

• Not recommended for patients under 18 years, as this population was excluded from all phase 3 clinical trials 1, 2

Kidney Transplant Recipients

• Use caution in kidney transplant recipients due to limited data and potential concerns about HIF-PHIs affecting immune cell function 1, 2

Relative Contraindications and Cautions

• Exercise caution in patients with cardiovascular disease history due to absence of large cardiovascular outcomes trials comparable to other HIF-PHIs (daprodustat, vadadustat, roxadustat) 2
• Avoid use in patients with history of stroke, similar to ESA recommendations 5
• Use caution in ESA-hyporesponsive patients without supporting evidence, as data in this subgroup are limited 2
• Exercise caution in patients with marked systemic inflammation; trial participants with elevated C-reactive protein showed only modest hemoglobin responses 2

Critical Safety Principles

Hemoglobin Targets

• Never intentionally increase hemoglobin above 13 g/dL (1A recommendation from KDIGO) 5
• Target range of 10-12 g/dL balances benefits of reducing transfusions and anemia symptoms against cardiovascular risks 5, 1
• Multiple large trials demonstrate increased cardiovascular events, stroke, and mortality when hemoglobin exceeds 12 g/dL 2, 6

Combination Therapy

• Never combine desidustat with erythropoietin or other ESAs, as this creates additive erythropoietic stimulation with substantially increased risk of exceeding safe hemoglobin targets 6
• The only exception involves hydroxyurea with EPO in sickle cell disease patients with CKD, which does not apply to desidustat 6

Practical Advantages

• Oral administration eliminates injection-related pain and improves convenience, particularly beneficial for non-dialysis and peritoneal dialysis patients 1, 2
• May enhance enteric iron absorption and iron utilization through hepcidin reduction, potentially beneficial in functional iron deficiency states 2
• The DREAM-ND trial showed statistically significant reduction in hepcidin levels at weeks 12 and 24 compared to darbepoetin 3

Common Pitfalls to Avoid

• Do not initiate desidustat without first correcting iron deficiency (TSAT ≤30%, ferritin ≤500 ng/ml) 5, 6
• Do not target hemoglobin levels above 11.5 g/dL in general practice, as individualization above this level requires careful risk-benefit assessment 5
• Do not use desidustat as first-line therapy without considering iron supplementation trials first, particularly in non-dialysis patients 5
• Recognize that desidustat has more limited long-term cardiovascular safety data compared to other HIF-PHIs with extensive outcomes trials 1, 2