Clinical and Genetic Markers of Erythropoietin Deficiency Anemia in Chronic Kidney Disease (Predialysis) Patients

Abstract

Aim: To determine the clinical and genetic markers associated with erythropoietin deficiency anemia in predialysis individuals. Materials & methods: Patients were categorized into cases and control group. Demographic characteristics and clinical parameters were obtained from medical record review and serum EPO and ferritin were obtained with ELISA. HIF-1α (rs2057482), IL-1β (rs1143627) and EPO (rs1617640) gene polymorphism were genotyped. Results: Female gender, glomerular filtration rate, treatment with hematinics, anticoagulant and diuretic were strong predictors of EPO-deficient anemia in predialysis chronic kidney disease patients. Genetic polymorphism in the HIF-1α recessive model was associated with non-EPO-deficiency, followed by EPO recessive allele associated with low-serum erythropoietin and IL-1β recessive model with low hemoglobin level. Conclusion: EPO-deficiency anemia can be diagnosed more conveniently in the presence of biomarkers.

Heritability and association with distinct genetic loci of erythropoietin levels in the general population

“…Interestingly, the top common SNP of our study (rs9402685) and the associated HBS1L-MYB locus showed a robust association with Epo levels ( P =1.46 x10 -4 ), confirming the previously published results. 4 The SNP rs1617640 of the EPO locus itself has been reported to be associated with low Epo serum levels in predialysis chronic kidney disease patients, 9 but neither this SNP nor any other SNP of the EPO locus (lowest P =0.17 at rs7789679) were associated with Epo levels in our study.…”

Sickle cell disease as an accelerated aging syndrome

“…Nephropathy is generally a progressive disease, which is associated with endocrine failure (erythropoietin and 1,25-dihydroxycholecalciferol) with attendant systemic effects that resemble accelerated aging. 56,57 Inadequate secretion of erythropoietin by the kidney in response to low hemoglobin drive aggravates chronic hemolytic anemia of SCD and might even result in transfusion dependence. Uremia also reduces erythrocyte survival by damaging red cell membrane, making them prone to phagocytosis by the macrophages in the reticuloendothelial system.…”

“…58 There could also be nutritional anemia from malnutrition and dialysis-related nutrients deficiency, in addition to increased hepcidin that interferes with intestinal absorption of iron. 57 The other important endocrine dysfunction associated with the nephropathy is abnormal vitamin D metabolism. Calcium absorption from the gastrointestinal tract is regulated by an active vitamin D called 1,25-dihydroxycholecalciferol (calcitriol), which is produced by the kidney.…”