HIGH DOSE ERYTHROPOIETIN VERSUS DESIDUSTAT FOR TREATMENT OF ANEMIA IN PATIENTS OF CHRONIC KIDNEY DISEASE HAVING INADEQUATE RESPONSE TO WEIGHT BASED ERYTHROPOIETIN DOSE: PROSPECTIVE OBSERVATIONAL STUDY

Introduction:

Chronic kidney disease (CKD) often results in anemia due to decreased erythropoietin (EPO) production and impaired erythropoiesis. Anemia (hemoglobin levels below 13 g/dl in males and 12 g/dl in females) reduces oxygen delivery, leading to fatigue, decreased exercise capacity, sometimes causing cardiac complications and increased mortality. Conventional high-dose EPO therapy has been associated with adverse events like thrombosis. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) like desidustat boost endogenous EPO production and enhance iron metabolism.

Methods:

This pilot observational study was conducted at a tertiary care institute in India to compare the efficacy and adverse effect profile of high-dose EPO versus desidustat in CKD patients with anaemia having inadequate response to weight-based dosing of EPO.

Consecutive patients were recruited and their baseline hemoglobin, blood pressure, iron profile and inflammatory markers were noted. The patients were followed up monthly to monitor adverse effects and the workup was repeated at the two-month follow-up.

Results:

Forty-four patients were recruited, 23 received desidustat and 21 received high-dose EPO. The mean age of patients was 41.59 years. The mean rise in haemoglobin in the desidustat group (1.19±1.27 g/dl, p<0.001) and high-dose EPO group (1.27±0.81 g/dl, p<0.001) was comparable (p=0.591).  Decrease in blood pressure was noted in both groups but was statistically insignificant. The mean decrease in ferritin was slightly higher in the high-dose EPO group (303.32±1415.89 ng/ml) compared to the desidustat group (283.95±478.14 ng/ml), however, it was statistically insignificant (p=0.06). Changes in serum iron levels, transferrin saturation and total iron binding capacity were comparable in both the groups (p=0.902, 0.696, and 0.683 respectively). A comparable (p=0.372) decrease in hepcidin concentration was noted in the desidustat (27.29±16.70 ng/ml, p=0.464) and the high-dose EPO group (83.85±21.08 ng/ml, p=0.042). The decrease in C-reactive protein was not significantly different (p=0.262) between the desidustat (0.72±6.61 mg/l) and the high-dose EPO group (2.85±6.73 mg/l), as was erythrocyte sedimentation rate (desidustat–14.13±26.09 mm/hour; high-dose EPO–1.68±18.12 mm/hour, p=0.076). The interleukins, IL-1 and IL-6 were found to be non-normally distributed. In the desidustat group, the median decrease in IL-1 was 1.54 pg/ml (IQR-229.93, p=0.314) while increase in IL-6 was 1.21pg/ml (IQR-13.79, p=0.279). The high-dose EPO group revealed a median increase of 1.54 pg/ml (IQR-229.93, p=0.996) in IL-1 and decrease in IL-6 (71.29 pg/ml, IQR-581.17, p=0.001). Adverse effects with desidustat included metallic taste, vomiting, and uncontrolled hypertension. In the EPO group, one patient experienced hypertension and brachiocephalic stenosis each.

Conclusions:

Both desidustat and high-dose EPO effectively increased hemoglobin levels in CKD patients unresponsive to standard EPO therapy. Desidustat showed comparable efficacy with a similar safety profile, making it a viable alternative. Oral administration of desidustat and its ability to modulate inflammation and iron metabolism offer a promising therapeutic option. Further research with larger cohorts is recommended to validate these findings and assess long-term outcomes.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.