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.

The level of erythropoietin (Ep) was measured in sera and urine from aplastic anemia patients. Increased levels of Ep were demonstrated in sera from all 25 patients studied. An elevated level of Ep was found in the urine of 17 of 23 patients in whom the urine was tested. No correlation between blood hemoglobin and Ep level was observed. A higher serum Ep level was noted in patients with aplastic anemia than in patients with sideropenic anemia of the same severity. To explain the discrepancy diminished Ep consumption in bone marrow of aplastic anemia patients is discussed.

The rHuEpo effect on anemia in eight renal transplant patients (group A) with severe anemia (Hb 6.0-7.5 g/dL) and chronic graft failure (CGF) (sCr 281-794 mumol/L) was compared to the rHuEpo effect on anemia in predialysis (20 patients-group B) and hemodialysis patients (17 patients-group C) in order to examine the rHuEpo effect on anemia and graft failure progression, and to find out whether the response to therapy in these three patient groups differed. Although renal function impairment was similar in patients from group A and B, anemia was more severe in patients from group A. Serum immunoreactive erythropoietin levels were within normal limits for nonanemic persons, that is, inadequate for the level of anemia in all patients before therapy. Maintenance immunosuppression given after renal transplantation consisted of cyclosporine, azathioprine, and prednisone in standard doses. The startig rHuEpo dose of 150 U/kg/wk increased by 25 U/kg if the target Hb of 10.0 g/dL was not achieved at the end of a 4-week period. When target Hb was achieved, the rHuEpo dose was regularly adjusted to maintain Hb of 10.0 g/dL. Most patients from group A and group C were polytransfused before rHuEpo therapy and consequently with iron overload so that only some patients from these groups and all predialysis patients needed iron supplementation given orally. Anemia improved in all patients with 2 to 10 weeks of treatment. Mean rHuEpo doses for the first 2 months were similar in three studied groups, but the patients with the lowest initial hemoglobin values responded better to rHuEpo therapy. The rate of Hb increase during the initial phase of therapy was significantly higher in patients from group A and B comparing to patients from group C, indicating the importance of residual renal function for rHuEpo effect on anemia. Progression of CGF expressed by the slope of l/sCr vs. time did not change in either patients from group A or in predialysis patients. It could be concluded that rHuEpo therapy improved anemia in transplant patients as in predialysis and hemodialysis patients. Anemia improvement by rHuEpo did not accelerate the progression of graft function.

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