Potential Association Between Darbepoetin Alfa Administration and Reduced Proteinuria in Real-World Clinical Practice: A Post Hoc Analysis of the BRIGHTEN Study.

AIM: Erythropoiesis-stimulating agents (ESAs) may be associated with inhibition of urinary protein; however, information from large-scale real-world clinical settings is insufficient. We aimed to investigate whether darbepoetin alfa (DA) was associated with reduced proteinuria in patients with chronic kidney disease (CKD) using data from the 'oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN)' observational study.

METHODS: In total, 1161 patients treated with DA were analysed, including 307 with diabetic kidney disease (DKD), 286 with nephrosclerosis and 285 with chronic glomerulonephritis. We estimated the nonlinear relationship between DA dose and change in urinary protein-creatinine ratio (UPCR) at 12 weeks using a spline curve. We also explored the potential clinical relevance of the association between higher DA doses and changes in proteinuria by comparing the slope of DA dosage and UPCR reduction between patients with high and low ESA resistance, which is associated with CKD prognosis.

RESULTS: The UPCR appeared to decrease as the DA dose exceeded 50 μg, particularly in the DKD group. The slopes of DA dosage and UPCR reduction significantly differed (p = 0.009) between the high- and low-ESA resistance groups, especially in patients with DKD (p < 0.001). This difference was maintained after adjustment for factors such as the presence or absence of renin-angiotensin-aldosterone system inhibitors and blood pressure variability during the study period.

CONCLUSION: DA administration was associated with reduced proteinuria in a dose-dependent manner, particularly in patients with DKD.