Erythropoietin and Anemia in the Progression of Balkan Endemic Nephropathy and Other Renal Diseases

Abstract

We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia.

Influence of Body Iron Stores on the Serum Erythropoietin Concentration in Hemodialyzed Patients

“…In uremic patients erythropoietin levels remain with in or only slightly above the normal range, and they are much lower than those observed in non-renal anemias of comparable severity [3,4], Furthermore, an inverse rela tionship between hemoglobin and erythropoietin levels does not exist [5,6]. In this situation the hemoglobin con centration ceases to be the most important factor regulat ing the production of erythropoietin.…”

Anaemia in Diabetes: An Emerging Complication of Microvascular Disease

“…1) [19]. At oxygen concentrations less than 4-5% extracellular O 2 (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) [20], ubiquitination and proteosomal degradation of HIF-α are inhibited [21] and the activity of the HIF-α trans-activation domains is increased [22], allowing HIF-α to dimerise with HIF-ß. The resulting active HIF-1 protein complex binds to the active site on the enhancer region in the 3' flanking region of the erythropoietin gene, leading to increased production of erythropoietin.…”

“…However, the inverse relationship between plasma erythropoietin activity and blood haemoglobin concentration is better maintained in chronic glomerulonephritis than in non-glomerular renal diseases [27]. For example, in one study patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher red cell parameters than the patients from the same subgroup with tubulointerstitial nephropathies [28]. However, by the time patients developed severe renal failure, serum erythropoietin levels were inappropriately low for the degree of anaemia in both groups.…”

Diagnostic Criteria for Balkan Endemic Nephropathy: Proposal by an International Panel

“…[18] Importantly, BEN patients undergoing dialysis require higher doses of erythropoietin for anemia treatment than other patients with end-stage kidney disease (ESKD). [19,20] …”