Serum Erythropoietin Levels In Patients Research Articles

Serum Erythropoietin in Patients with Chronic Renal Failure in the Predialysis Stage

Summary A prospective study was carried out of serum erythropoietin levels in patients with chronic renal failure/chronic kidney disease in the predialysis period. The study is part of scientific project № 2/2022, financed by Medical University-Pleven. Fifty patients were tested – 22 males and 28 females (average age 63.7±13.0), with average serum creatinine 253±127 mcmol/l and average glomerular filtration rate of 22.6±11.8 ml/min/1,72 m2. The results showed that the serum erythropoietin level varied from 1.86 to 48.50 U/l and was below the borderline in only three patients. There were no significant differences between serum erythropoietin and haemoglobin values in both genders. No differences were found between the average haemoglobin values of patients with different values of serum erythropoietin. Non-significant differences were found in the values of serum erythropoietin in patients with different haemoglobin values. A statistically significant difference between the average value of serum erythropoietin was seen in the group of patients who were not undergoing treatment for anaemia with recombinant erythropoietin (8.5±5.9 U/l) and the groups treated with a dose above 3000 UI/weakly (from 18.6±11.3 to 19.7±8.8 U/l).

Detection and clinical significance of serum EPO levels in patients with haematological tumours.

This experiment aimed to detect serum erythropoietin (EPO) levels in patients with haematological tumours and to investigate its clinical significance. For this purpose, 110 patients with haematological tumours admitted to our hospital between January 2019 and December 2020 were selected as the study population according to the inclusion and exclusion criteria, and they were included in the case group, and the clinical data of the patients were retrospectively analysed. 90 cases of people without hematological tumors who underwent physical examination during the same period were also included as a control group. The serum EPO levels of the two study groups were compared, and the clinical diagnostic value of EPO was analysed using the subject operating characteristic curve (ROC). Results indicated that of the 110 patients, 56 were leukaemia patients, 24 were multiple myeloma patients and 30 were malignant lymphoma patients. The differences in gender, age, disease history, alcohol consumption and smoking history between the two groups were not significant (P>0.05), while the EPO levels in the control group were significantly lower than those in the case group, with a statistical significant difference of P<0.05. The EPO levels in patients with leukaemia, multiple myeloma and malignant lymphoma were (165.43± 20.46) mU/mL, ( 28.14± 4.51) mU/mL and (86.25±10.33) mU/mL significantly higher than the control group, with a significant difference of P<0.05. Using the absence of haematological tumours as a control, the analysis yielded an area under the ROC curve of 0.995 for EPO diagnosis in patients with leukaemia, a 95% confidence interval of 0.987 to 1.000, a sensitivity of 97.80%, with a sensitivity of 98.2 %; the area under the ROC curve for patients with multiple myeloma was 0.910, with a 95% confidence interval of 0.818 to 1.000, with a sensitivity of 98.90% and specificity of 87.50%; the area under the ROC curve for patients with malignant lymphoma was 0.992, with a 95% confidence interval of 0.978 to 1.000, with a sensitivity of 96.70% and specificity of 96.70%. In conclusion, the serum EPO levels of patients with haematological tumours are significantly higher than those of the normal population, and the detection of serum EPO levels is valuable for the diagnosis of clinical haematological tumours.

ASSESSMENT OF ERYTHROPOIETIN STATUS IN EARLY DIABETIC NEPHROPATHY AND ITS CORRELATION WITH MICROALBUMINURIA

Objectives: To investigate serum Erythropoietin levels in patients with early diabetic nephropathy (&lt;5 years) and analyze the relationship between Erythropoietin and Microalbuminuria. Methods: Case population comprised of Type 2 diabetic patients in the age group 18-60 years with diabetes persisting for less than 5 years. Diagnostic criteria for case subject with diabetics was done as per ADA 2016 guidelines. A control group of healthy subjects was used for comparison. Results: Our study shows that Erythropoietin level is signicantly decreased in cases in comparison to controls (p value &lt;0.05). A negative correlation exists between Erythropoietin level and ACR value in cases and also a negative correlation exist between ACR and hemoglobin level in cases. Conclusion: Early Diabetic nephropathy is associated with decreased Erythropoietin level in spite of normal iron storage that warrant frequent monitoring among patients with diabetic kidney disease.

Fresh Pomegranate Juice Decreases Fasting Serum Erythropoietin in Patients with Type 2 Diabetes.

Pomegranate juice (PJ) has been recognized to have various biological benefits in several pathological conditions. One such benefit is the augmentation of hemoglobin level and the number of erythrocytes in the human body. Here, we assessed the short-term effect of fresh PJ on the level of Erythropoietin (EPO) in patients with type 2 diabetes (T2D) compared to healthy individuals. Blood samples from 59 participants with T2D and 30 healthy individuals were collected after a 12-hour fast and 3 hours after administration of fresh PJ at 1.5 mL per kg body weight. Serum glucose was measured by standard method and commercially available chemiluminescent immunoassay kits were used to determine serum EPO concentration. Mean changes in serum EPO levels 3 hours after ingesting PJ and before the juice ingestion (EPO response to PJ) for both diabetic and healthy participants were -2.002 ± 0.541 vs. - 0.041 ± 0.214, respectively (P = 0.0087). This EPO response to PJ was found not to be correlated with age (P = 0.6622) and gender (P = 0.5354) for patients with T2D, while a negative correlation (P = 0.0183) between EPO response to PJ and fasting serum glucose concentrations was observed in these patients. In conclusion, fresh PJ reduced serum EPO level in patients with T2D, but not in healthy individuals, 3 hours after ingesting the juice. The EPO response to PJ was found to be negatively correlated with fasting serum glucose, but not with age and gender, of patients with T2D. This trial is registered with ClinicalTrials.gov Identifier. NCT03902288.

Role of serum erythropoietin level in patients with absolute erythrocytosis

PRV is a myeloproliferative disorder with an acquired genetic mutation involving the stem cell. Erythropoietin (Epo) is a hemopoietic growth factor which provides some guidance to the diagnosis of PRV. The study was done to evaluate the diagnostic significance of erythropoietin level in PRV and its role in pre and post treated PRVpatients.The study includes (47) patients diagnosed as PRV including (31) males and (16) females with age range (20- 77 years). The criteria for diagnosis of polycythemia is PCV &gt; 52% and/ or Hb ≥18.5 gm/dl for male and PCV &gt;48%and/ or Hb ≥16.5 gm/dl for female.The investigations which were done for all new patients including CBC, blood films and serum Epo, in addition to the BM examination for new indicated cases of PRV. Follow up of old PRV (31) patients were done by PCV and serum Epo. We found thatthe mean Epo was 9.82mIU/ml. There was no statistical significant correlation between Epo mean and mean of other parameters.There was a statistical significance between pre and post treated cases regarding mean PCV and Epo. The acceptible EPO cutoff level to define PRV of (4.9) with sensitivity (71.4), specificity (86.7) and(p&lt;0.001). So, we conclude that the serum Epo level was a simple reliable test for diagnosis of PRV with a cutoff value of (4.9) andthere was a significant difference between treated and untreated cases of PRV regarding PCV and Epo.

Clinical Significance of the Serum EPO Level in Patients with Iron Deficiency Anemia

To investigate the expression level of erythropoietin (EPO) and ferritin before and after treatment of patients with iron deficiency anemia (IDA) so as to explore their clinical significance in diagnosis and discrimination. The EPO and ferritin levels in serum of 37 patients with IDA were determined by using chemiluminescence analysis (CLIA method) and electrical chemiluminescence analysis (ECLIA method), 30 healthy people were randomly selected as normal controls. (1) the sEPO level in IDA patients of group before treatment, group treated for 1 month and group treated for 2 months was higher than that in normal control group (P < 0.05). The level of sEPO of IDA patients in different groups after treatment was lower than that in IDA patients of groups before treatment, along with improvement of anemia status, the level of EPO was gradually reduced, and the level of sEPO in patients of group treated for 3 months was not statistical significant in comparison with that in normal control (P > 0.05). The level of ferritin in IDA patients before and after treatment was lower than that in normal control group (P < 0.05). The level of ferritin in IDA patient of groups after treatment was all higher than that in patients of groups before treatment, but comparision of serum ferritin level in patients of groups after treatment did not show statistical significance. (2) The level of logEPO in IDA patient before and after treatment was negatively related with level of Hb, but the level of ferritin in IDA patients was positively related with the level of Hb before treatment (r = 0.449, P = 0.005), the level of ferritin in patients of different group after treatment and in normal group did not related with level of HB. (3) The level of serum EPO in patients of severe anemia group was obviously higher than that in patients of moderate and mild anemia groups, and along with aggravation of anemia, the EPO level was gradually arised. The serum EPO is involved in the process of erythrocyte hematopoiesis, and can indicate the level of anemia, its sensitivity for anemia is higher than that of ferritin, and has important clinical value for evaluating status of diseases, observing therapeutic efficacy and judging prognosisi of IDA.

Aqueous humor and serum erythropoietin levels in patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma

A prospective, non-randomized, comparative study was carried out to investigate aqueous humor and serum erythropoietin (EPO) levels in patients with pseudoexfoliation syndrome (PXS), pseudoexfoliative glaucoma (PXG), and, as controls, senile cataract without glaucoma. Aqueous humor was aspirated at the beginning of cataract or combined glaucoma-cataract surgery from 24 patients with PXS, 24 patients with PXG, and 24 patients with cataract only. Venous blood samples were obtained from all patients at the same time. Levels of EPO were measured in aqueous humor and venous blood using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. There was no statistically significant difference between the mean aqueous humor EPO concentrations in eyes with PXS (10.70 ± 7.18 mU/ml), PXG (10.18 ± 7.20 mU/ml) and controls (9.75 ± 5.04 mU/ml) (P = 0.732). There was no statistically significant difference between the mean serum EPO concentrations in eyes with PXS (6.32 ± 2.86 mU/ml), PXG (7.06 ± 4.35 mU/ml) and controls (7.30 ± 4.15 mU/ml) (P = 0.672). Contrary to predictions based on the relation with ischemic processes, no difference was revealed between levels of EPO in aqueous humor and serum in patients with PXS and PXG.

Serum erythropoietin levels in patients with central serous chorioretinopathy.

To evaluate the levels of erythropoietin (EPO) in the serum in patients with central serous chorioretinopathy (CSC). An institutional comperative clinical study. The serum EPO levels were measured with the enzyme-linked immunosorbent assay (ELISA) method, of 15 patients with active CSC (Group 1), 15 patients with inactive CSC (Group 2) and 15 healthy volunteers (Group 3). Kruskal-Wallis variance analysis and Mann-Whitney U test were used for statistical analysis. The patient and control groups were matched for age and sex. There was no statistically significant variation with regard to age and gender among the groups (P > 0.05). The mean serum EPO concentrations in patients with active CSC (Group 1), inactive CSC (Group 2) and in healthy controls (Group 3) were 11.39 ± 3.01 mlU/mL, 11.79 ± 3.78 mlU/mL and 11.95 ± 3.27 mlU/mL, respectively. There was no significant variation among the serum EPO concentrations of the study groups (P > 0.05). These findings suggest no role of serum EPO in pathogenesis of CSC.

Pathogenesis of Renal Anemia

Anemia is a common complication of chronic kidney disease. Although mechanisms involved in the pathogenesis of renal anemia include chronic inflammation, iron deficiency, and shortened half-life of erythrocytes, the primary cause is deficiency of erythropoietin (EPO). Serum EPO levels in patients with chronic kidney disease are usually within the normal range and thus fail to show an appropriate increase with decreasing hemoglobin levels, as found in nonrenal anemias. Studies elucidating the regulation of EPO expression led to the identification of the hypoxia inducible factor-hypoxia responsive element system. However, despite much progress in understanding the molecular mechanisms through which cells can sense oxygen availability and translate this information into altered gene expression, the reason why EPO production is inappropriately low in diseased kidneys remains incompletely understood. Both alterations in the function of EPO-producing cells and perturbations of the oxygen-sensing mechanism in the kidney may contribute. As with other anemias, the consequences of renal anemia are a moderate decrease in tissue oxygen tensions and counterregulatory mechanisms that maintain total oxygen consumption, including a persistent increase in cardiac output.

Elevated serum erythropoietin levels in patients with Budd‐Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis

It is widely accepted that an increased serum endogenous erythropoietin (Epo) level in a patient presenting with an elevated red cell mass makes a diagnosis of clonal polycythemia vera (PV) extremely unlikely. However, until the recent description of the constitutively activating V617F point mutation of the Janus 2 tyrosine kinase (JAK2)--a high-frequency molecular marker that is extremely specific for clonal chronic myeloproliferative disorders--distinction of PV from secondary erythrocytosis or other conditions has often been difficult. The purpose of this study was to use JAK2 V617F analysis to re-evaluate the validity of elevated Epo levels as a PV-exclusion criterion in patients with hepatic vein thrombosis [Budd-Chiari syndrome (BCS)]. We reviewed clinical data from 30 patients at our institution who presented with erythrocytosis and BCS. We isolated myeloid cells from fresh or archival bone marrow samples from four patients with BCS and an elevated serum Epo level, and analyzed them for the presence of the JAK2 V617F mutation. All four samples were positive for JAK2 V617F, confirming the presence of a clonal hematopoietic disorder consistent with PV. In the presence of BCS, elevated serum Epo levels do not exclude the diagnosis of PV.

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (>1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia. Am. J. Hematol. 57:113–118, 1998. © 1998 Wiley-Liss, Inc.

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes.

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (> 1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia.

Serum Erythropoietin Levels in Patients with Beta Thalassemia Major and Intermedia

Serum erythropoietin (EPO) levels were determined by radioimmunoassay in 37 β-thalassemia patients, the phenotype being thalassemia major (TM) in 30 and thalassemia intermedia (TI) in 7. The control group consisted of 37 healthy children. The mean serum EPO levels were significantly higher in patients with both TM (215.1 ± 144.5) and TI (53.8 ± 40.2) compared with the control group (9.3 ± 4.6). Although the mean hemoglobin (Hb) concentrations in the patients with TM and TI were similar (8.6 ± 0.9 and 8.7 ± 1.1, respectively), the mean serum EPO level was significantly higher in TM patients than the patients with TI (P ± 01). This finding may indicate that some other factors contributing to the metabolic adaptation to low oxygen concentration or improvement of the tissue oxygenation are as effective as the Hb concentration in EPO production. It is also suggestive of the fact that some amount of tissue hypoxia cannot be prevented in spite of polytransfusion regimens in TM patients. Serum EPO levels of TM patients were not found to be age related or correlated with the mean pretransfusional Hb levels. In the TM patients, the serum EPO concentration was not consistently correlated with clinical signs of erythropoietic activity. This may be indicative of personal differences with respect to the sensitivities of erythroid precursors to the increasing EPO level in TM patients.

Serum erythropoietin levels in patients with sepsis and septic shock.

The role of the immune system in the control of the production of erythropoietin is still poorly understood. Herein, the levels of circulating immunoreactive erythropoietin, tumour necrosis factor alpha, interleukin-1 beta and interleukin-6 were determined in 10 septic patients for up to 4 d following the admission to an internal intensive care unit. The data show that the production of erythropoietin was not suppressed despite an increase in the levels of proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin level in the nonsurvivors resembled that of acute phase proteins and was independent of the blood haemoglobin concentration. Similar to interleukin 6, abnormally high serum erythropoietin levels appear to be a negative prognostic indicator in patients suffering from septic shock.

Serum erythropoietin levels in patients with solid tumours

Patients with malignant disease frequently develop anaemia. To investigate the role of erythropoietin (EPO) in this anaemia, serum levels were determined in patients with solid tumours. The study population consisted of 84 patients (44 males, 40 females) with solid tumours and 99 healthy control subjects, and 13 84 patients were anaemic. Serum EPO was clearly elevated in the anaemic tumour patients, but this increase was less than in patients suffering from iron deficiency anaemia. As in iron deficiency anaemia, the correlation between EPO levels and haemoglobin values was inverse. When compared to healthy control subjects, the levels of EPO in the tumour patients without anaemia were decreased. We conclude that there may be an inhibition in the expression or secretion of EPO in patients with solid tumours which, as yet, has not been further defined. Based on this, the treatment of anaemia in cancer patients with erythropoietin appears promising.

Clinical Significance of Serum Erythropoietin Levels in Patients with Multiple Myeloma

Clinical Significance of Serum Erythropoietin Levels in Patients with Multiple Myeloma

Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post- BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Serum Erythropoietin Levels in Patients Receiving Intensive Chemotherapy and Radiotherapy

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Serum erythropoietin levels in patients with congenital heart disease

Serum erythropoietin levels were measured by radioimmunoassay in 146 children and young adults with congenital heart disease to assess the relationship between erythropoietin and clinical factors (heart failure, anemia, cyanosis) and hemodynamic variables affecting oxygen delivery and utilization. Erythropoietin values were in the normal range (10 to 30 microU/mL) in 73% (58 of 80) of the patients with and 82% (54 of 66) of those without cyanosis. Elevated erythropoietin values in cyanotic patients were associated with lower mixed venous oxygen saturation and tension than in cyanotic patients with normal erythropoietin levels, even though the degree of polycythemia was similar. In contrast, most of the acyanotic patients who had elevated erythropoietin levels were anemic. Of the blood oxygen measurements, mixed venous oxygen saturation and tension had the closest inverse correlation with erythropoietin values. The normal erythropoietin values in most patients are in accord with other observations that show that an elevation in erythropoietin level in response to hypoxia will be transient if it results in a rise in hemoglobin concentration "appropriate" to the degree of hypoxia. Persistent elevation of erythropoietin in patients with congenital heart disease may indicate harmful impairment of hemoglobin production that is potentially correctable.

Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency

AbstractErythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. The relative importance of erythropoietin (Ep) and inhibition of erythropoiesis in the anemia of chronic renal insufficiency has been investigated. Sixty patients with varying degrees of renal insufficiency, 40 normal subjects and 40 patients with anemia and normal renal function, were studied. Erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell colony formation were assayed in fetal mouse liver and human bone marrow cultures, respectively. Erythropoietin was measured by radioimmunoassay. Hematocrit and plasma creatinine concentration correlated with the degree of serum inhibition of CFU-E formation (r = 0.69, P < 0.001, and r = 0.62, P < 0.001, respectively). Serum erythropoietin levels in patients with renal insufficiency (34.4 ± 6.7 mU/ml) were slightly higher than normal values (23.1 ± 0.98 mU/ml), but showed no relationship to plasma creatinine, hematocrit, or inhibition of CFU-E formation. In contrast, serum erythropoietin concentrations increased exponentially as the hematocrit decreased below 32% (r = 0.61, P < 0.001), and CFU-E formation was stimulated by serum in anemia patients with normal renal function. Studies of granulopoiesis showed uremic sera supported in vitro CFU-GM growth more efficiently than sera from normal subjects. These results suggest that inhibition of erythroid, but not granulocytic, progenitor cell formation, in addition to a relative erythropoietin deficiency, are the primary factors responsible for the anemia of chronic renal failure.Déficit en érythropoïétine et inhibition de l'érythropoïèse au cours de l'insuffisance rénale. L'importance relative de l'érythropoiétine (Ep) et l'inhibition de l'érythropoïèse lors de l'anémie de l'insuffisance rénale chronique ont été étudiées. Soixante malades avec des degrés variables d'insuffisance rénale, 40 sujets normaux et 40 malades avec une anémie et une fonction rénale normale, ont été étudiés. La formation de colonies cellulaires souches érythroïde (CFU-E) et granulocytaire (CFU-GM) ont été mesurées dans du foie foetal de souris et dans des cultures de moelle osseuse humaine, respectivement. L'érythropoiétine a été mesurée par dosage radioimmunologique. L'hématocrite et la concentration plasmatique de créatinine étaient corrélées avec le degré d'inhibition sérique de la formation de CFU-E (r = 0,69, P < 0,001 ; et r = 0,62, P < 0,001, respectivement). Les niveaux d'érythropoïétine sérique chez les malades atteints d'insuffisance rénale (34,4 ± 6,7 mU/ml) étaient légèrement plus élevés que les valeurs normales (23,1 ± 0,98 mU/ml), mais il n'y avait pas de relation avec la créatininémie, l'hématocrite, ou l'inhibition de formation de CFU-E. A l'opposé, les concentrations d'érythropoïétine sérique s'élevaient exponentiellement au fur et à mesure que l'hématocrite diminuait en dessous de 32% (r = 0,61, P < 0,001), et la formation de CFU-E était stimulée par du sérum chez des malades anémiques avec une fonction rénale normale. Des études de la granulopoïèse ont montré que les sérums urémiques supportaient la croissance in vitro de CFU-GM de façon plus efficace que les sérums de sujets normaux. Ces résultats suggèrent que l'inhibition de formation de cellules souches érythroïdes et non granulocytaires, en plus d'un relatif déficit en érythropoïétine, sont les facteurs primaires responsables de l'anémie de l'insuffisance rénale chronique.