Genetic Variants (HIF1α, ACE I/D, STIM1, ORAI1 and TMPRSS6) on Erythropoietin Resistance in Dialysis Patients with Chronic Kidney Disease: Scoping Review

Background Anemia is one of the most important chronic kidney disease (CKD) complications that usually managed with Erythropoietin Stimulating Agent (ESA). Some factors are responsible for ESA response included genetic predisposition. This review aimed to summarize variant genetics of HIF1α, ACE I/D, STIM1, ORAI1, and TMPRSS6 that are associated with EPO resistance in hemodialysis patients Materials and Methods Seven databases were searched through Scopus, PubMed, Cochrane Library, Proquest, Science Direct, Wiley, and EBSCOhost to identify potential articles. The year of publication ranges from 2012 to 2022. The study included dialysis patients who defined measures for the erythropoietin resistance index (ERI), body weight, and hemoglobin (Hb). Synthesis is done by grouping according to thematic analysis for elaborative results. Results and Discussion There are 2,712 articles in the initial registration, 7 articles met the eligible criteria. There were four studies about polymorphism of the ACE I/D gene, one study about minor alleles of STIMI and ORAI 1, one study about TMPRSS6, and one article study about HIF1α. ACE I/D polymorphisme showed some different effect, but patient with I/D allele tend to have lower Hb. STIM1 was associated with a lower risk of EPO resistance and ORAI1 was also associated with a higher risk of EPO resistance. The TMPRSS6 736V variant is associated with higher hepcidin levels in chronic hemodialysis patients. Conclusion These study showed many genetic variants affect the success of EPO therapy with different mechanisms. Genetic variants recognized earlier than therapy may help predict the effectiveness and efficiency of EPO therapy.