Discussion
renal anemia, CKD, proteinuria, anemia, ischemic organ damage, tissue damage, diabetes
RENAL ANEMIA, ANEMIA, SECONDARY, EVENTS, DISEASES, DIABETES
In this prespecified secondary analysis of the PREDICT trial, we found that targeting a higher hemoglobin level at 11–13 g/dl with darbepoetin alfa did not improve eGFR and proteinuria slopes as compared to targeting a lower hemoglobin level at 9–11 g/dl in patients with advanced CKD without diabetes. These were in line with the results of the primary analysis in our study that a higher hemoglobin target did not reduce the composite renal outcome [In the FAS analyses of the eGFR and proteinuria slopes, which was the prespecified secondary endpoints, we could not demonstrate the clear benefit of higher hemoglobin targeting using darbepoetin alfa. The composite renal endpoint was reduced by 22% in the high-hemoglobulin group (vs. low-hemoglobin group) as reported previously [As aforementioned, a meta-analysis has demonstrated the potential harm of targeting a higher hemoglobin level (> 13 g/dl) using ESAs in patients with CKD not requiring dialysis [However, the results of the PPS analysis need to be interpreted with caution. Hypo-responsiveness to ESAs was reported to be associated with worse kidney outcomes and CV prognosis [Concerning the mechanisms of ESAs on the CV prognosis and renal outcomes, both beneficial and harmful effects have been postulated. The beneficial effects for organ protection may be independent of anemia correction but can be attributed to the non-hematological effects of rHuEPO that prevent tissue damage [Regarding the other factors, male sex and higher urinary protein levels at baseline were independently associated with worse renal outcomes in line with those of previous studies [Recently, HIF-PHIs have been utilized in treating renal anemia in patients with CKD not requiring dialysis. Many preclinical studies have shown the potential benefit of HIF-PHIs for ischemic organ damage, including the heart and kidney [Our study had several potential limitations. First, only patients with CKD in Japan were included in the study, and Japan has a much lower incidence of CV events. Therefore, our results may underestimate the potential harm of CV diseases and may not be generalized to all patients with CKD in other places. Nevertheless, this could also be a strength of our study. Since the rates of CV events in our study were low, only 8% in the high- and 7% in the low-hemoglobin groups [