Also, it is to be noted that even if uremic toxins such as IS and PCS strongly aggravate anemia in advanced CKD and ESRD, renal anemia in this setting is primarily related to a decreased production of EPO by diseased kidneys (with interstitial fibrosis and reduced renal mass of cells producing EPO with the exception of genetic polycystic disease; cases of enlarged kidneys in diabetic and amyloid nephropathies with deposits of amorphous specific material have also a reduction of EPO-producing cells), together with a lowered set point for EPO production in case of hemorrhage. Here, EPO is linked to anemia.