The early-onset anemia in ADTKD-REN may stem from multiple pathways, including tubulointerstitial fibrosis-induced reduction in erythropoietin (EPO) secretion, renin deficiency due to REN mutations (which lowers angiotensin II levels, a stimulator of erythroid progenitor cells), and chronic inflammation or iron metabolism dysregulation. This evidence concerns the gene EPO and anemia (phenotype).