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Tungpo Huang - One of the best experts on this subject based on the ideXlab platform.

  • determinants of circulating soluble transferrin receptor level in chronic haemodialysis patients
    Nephrology Dialysis Transplantation, 2002
    Co-Authors: Dercherng Tarng, Tungpo Huang
    Abstract:

    Background. The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTf R) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment. Methods. In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, Reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTf R. HD patients received constant rHuEpo doses and basal sEpo was measured P86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log10 sTfR) as a dependent variable in the forward stepwise multiple regression model. Results. HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTf R, sEpo, and Reticulocyte Index. Univariate analyses showed that the sTf R level strongly correlated with sEpo (rs0.60, P-0.001) and % HRC (rs0.60, P-0.001), and significantly with serum ferritin (rs0.29, P-0.01), TS (rs0.27, P-0.05), and dose of rHuEpo administered (rs0.27, P-0.05) in HD patients. sTf R also had a positive correlation with haematocrit (rs0.26, P-0.05), red blood cell (RBC) count (rs0.23, P-0.05), and Reticulocyte count (rs0.24, P-0.05), but not with CRP (rs0.16, P)0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTf R level. Overall, the model explained 58.8% of the variability in sTfR (R 2 s0.588, P-0.001). Conclusions. Circulating sTf R is a good Index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTf R levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.

  • intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia
    Kidney International, 1999
    Co-Authors: Dercherng Tarng, Tungpo Huang, Yauhuei Wei, Benjamin I T Kuo, Wuchang Yang
    Abstract:

    Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Background Inadequate iron mobilization and defective iron utilization may cause recombinant erythropoietin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. We have demonstrated that intravenous ascorbic acid (IVAA), but not intravenous iron medication, can effectively circumvent the functional iron-deficient erythropoiesis associated with iron overload in HD patients. However, it is uncertain whether all HD patients with hyperferritinemia will consistently respond to IVAA and which Index may indicate functional iron deficiency in the special entity. Therefore, a prospective study was conducted to establish the guidelines for IVAA adjuvant therapy. Methods Sixty-five HD patients with serum ferritin levels of more than 500 μg/liter were recruited and divided into the control ( N = 19) and IVAA ( N = 46) groups. IVAA patients with a hematocrit (Hct) of less than 30% received 300mg of ascorbic acid three times per week for eight weeks. Controls had a Hct of more than 30% and did not receive the adjuvant therapy. Red blood cell and Reticulocyte counts, iron metabolism indices, erythrocyte zinc protoporphyrin (E-ZPP), and the concentrations of plasma ascorbate and oxalate were examined before and following the therapy. Results Thirteen patients (four controls and nine IVAA patients) withdrew by the end of the study. Eighteen patients had a dramatic response to IVAA with a significant increase in their hemoglobin and Reticulocyte Index and a concomitant 24% reduction in rEPO dose after eight weeks. This paralleled a significant rise in serum iron and transferrin saturation (TS) and a fall in E-ZPP and serum ferritin (baselines vs. 8weeks, serum iron 68 ± 37 vs. 124 ± 64 μg/dl, TS 27 ± 10 vs. 48 ± 19%, E-ZPP 123 ± 44 vs. 70 ± 13 μmol/mol heme, and serum ferritin 816 ± 435 vs. 587 ± 323 μg/liter, P N = 15) and in non-responders ( N = 19). Thirty-seven patients (18 responders and 19 non-responders) were further analyzed by receiver operating characteristic curves to seek the criteria for prediction of a response to IVAA treatment. The results showed that E-ZPP at a cut-off level of more than 105 μmol/mol heme and TS at a level of less than 25% were more specific to confirm the status of functional iron deficiency in iron-overloaded patients. The two criterion values had the highest accuracy to predict a response to treatment. Conclusions Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 μmol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.

Dercherng Tarng - One of the best experts on this subject based on the ideXlab platform.

  • determinants of circulating soluble transferrin receptor level in chronic haemodialysis patients
    Nephrology Dialysis Transplantation, 2002
    Co-Authors: Dercherng Tarng, Tungpo Huang
    Abstract:

    Background. The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTf R) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment. Methods. In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, Reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTf R. HD patients received constant rHuEpo doses and basal sEpo was measured P86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log10 sTfR) as a dependent variable in the forward stepwise multiple regression model. Results. HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTf R, sEpo, and Reticulocyte Index. Univariate analyses showed that the sTf R level strongly correlated with sEpo (rs0.60, P-0.001) and % HRC (rs0.60, P-0.001), and significantly with serum ferritin (rs0.29, P-0.01), TS (rs0.27, P-0.05), and dose of rHuEpo administered (rs0.27, P-0.05) in HD patients. sTf R also had a positive correlation with haematocrit (rs0.26, P-0.05), red blood cell (RBC) count (rs0.23, P-0.05), and Reticulocyte count (rs0.24, P-0.05), but not with CRP (rs0.16, P)0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTf R level. Overall, the model explained 58.8% of the variability in sTfR (R 2 s0.588, P-0.001). Conclusions. Circulating sTf R is a good Index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTf R levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.

  • intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia
    Kidney International, 1999
    Co-Authors: Dercherng Tarng, Tungpo Huang, Yauhuei Wei, Benjamin I T Kuo, Wuchang Yang
    Abstract:

    Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Background Inadequate iron mobilization and defective iron utilization may cause recombinant erythropoietin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. We have demonstrated that intravenous ascorbic acid (IVAA), but not intravenous iron medication, can effectively circumvent the functional iron-deficient erythropoiesis associated with iron overload in HD patients. However, it is uncertain whether all HD patients with hyperferritinemia will consistently respond to IVAA and which Index may indicate functional iron deficiency in the special entity. Therefore, a prospective study was conducted to establish the guidelines for IVAA adjuvant therapy. Methods Sixty-five HD patients with serum ferritin levels of more than 500 μg/liter were recruited and divided into the control ( N = 19) and IVAA ( N = 46) groups. IVAA patients with a hematocrit (Hct) of less than 30% received 300mg of ascorbic acid three times per week for eight weeks. Controls had a Hct of more than 30% and did not receive the adjuvant therapy. Red blood cell and Reticulocyte counts, iron metabolism indices, erythrocyte zinc protoporphyrin (E-ZPP), and the concentrations of plasma ascorbate and oxalate were examined before and following the therapy. Results Thirteen patients (four controls and nine IVAA patients) withdrew by the end of the study. Eighteen patients had a dramatic response to IVAA with a significant increase in their hemoglobin and Reticulocyte Index and a concomitant 24% reduction in rEPO dose after eight weeks. This paralleled a significant rise in serum iron and transferrin saturation (TS) and a fall in E-ZPP and serum ferritin (baselines vs. 8weeks, serum iron 68 ± 37 vs. 124 ± 64 μg/dl, TS 27 ± 10 vs. 48 ± 19%, E-ZPP 123 ± 44 vs. 70 ± 13 μmol/mol heme, and serum ferritin 816 ± 435 vs. 587 ± 323 μg/liter, P N = 15) and in non-responders ( N = 19). Thirty-seven patients (18 responders and 19 non-responders) were further analyzed by receiver operating characteristic curves to seek the criteria for prediction of a response to IVAA treatment. The results showed that E-ZPP at a cut-off level of more than 105 μmol/mol heme and TS at a level of less than 25% were more specific to confirm the status of functional iron deficiency in iron-overloaded patients. The two criterion values had the highest accuracy to predict a response to treatment. Conclusions Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 μmol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.

Muckenthaler M.u. - One of the best experts on this subject based on the ideXlab platform.

  • Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II
    2011
    Co-Authors: Casanovas G., Swinkels D.w., Altamura S., Schwarz K., Laarakkers C.m., Gross H.j., Wiesneth M., Heimpel H., Muckenthaler M.u.
    Abstract:

    Congenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree of anaemia (Hb), the response of erythropoiesis (Reticulocyte Index) as well as with iron availability in the serum (transferrin saturation). The observation that GDF15 is elevated in CDAII patients is consistent with the proposal that GDF15 is among the erythroid factors down-regulating hepcidin and contributing to iron overload in conditions of dyserythropoiesis

  • Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II
    'Springer Science and Business Media LLC', 2011
    Co-Authors: Casanovas G., Swinkels D.w., Altamura S., Schwarz K., Laarakkers C.m., Gross H.j., Wiesneth M., Heimpel H., Muckenthaler M.u.
    Abstract:

    Item does not contain fulltextCongenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree of anaemia (Hb), the response of erythropoiesis (Reticulocyte Index) as well as with iron availability in the serum (transferrin saturation). The observation that GDF15 is elevated in CDAII patients is consistent with the proposal that GDF15 is among the erythroid factors down-regulating hepcidin and contributing to iron overload in conditions of dyserythropoiesis

Wuchang Yang - One of the best experts on this subject based on the ideXlab platform.

  • intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia
    Kidney International, 1999
    Co-Authors: Dercherng Tarng, Tungpo Huang, Yauhuei Wei, Benjamin I T Kuo, Wuchang Yang
    Abstract:

    Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Background Inadequate iron mobilization and defective iron utilization may cause recombinant erythropoietin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. We have demonstrated that intravenous ascorbic acid (IVAA), but not intravenous iron medication, can effectively circumvent the functional iron-deficient erythropoiesis associated with iron overload in HD patients. However, it is uncertain whether all HD patients with hyperferritinemia will consistently respond to IVAA and which Index may indicate functional iron deficiency in the special entity. Therefore, a prospective study was conducted to establish the guidelines for IVAA adjuvant therapy. Methods Sixty-five HD patients with serum ferritin levels of more than 500 μg/liter were recruited and divided into the control ( N = 19) and IVAA ( N = 46) groups. IVAA patients with a hematocrit (Hct) of less than 30% received 300mg of ascorbic acid three times per week for eight weeks. Controls had a Hct of more than 30% and did not receive the adjuvant therapy. Red blood cell and Reticulocyte counts, iron metabolism indices, erythrocyte zinc protoporphyrin (E-ZPP), and the concentrations of plasma ascorbate and oxalate were examined before and following the therapy. Results Thirteen patients (four controls and nine IVAA patients) withdrew by the end of the study. Eighteen patients had a dramatic response to IVAA with a significant increase in their hemoglobin and Reticulocyte Index and a concomitant 24% reduction in rEPO dose after eight weeks. This paralleled a significant rise in serum iron and transferrin saturation (TS) and a fall in E-ZPP and serum ferritin (baselines vs. 8weeks, serum iron 68 ± 37 vs. 124 ± 64 μg/dl, TS 27 ± 10 vs. 48 ± 19%, E-ZPP 123 ± 44 vs. 70 ± 13 μmol/mol heme, and serum ferritin 816 ± 435 vs. 587 ± 323 μg/liter, P N = 15) and in non-responders ( N = 19). Thirty-seven patients (18 responders and 19 non-responders) were further analyzed by receiver operating characteristic curves to seek the criteria for prediction of a response to IVAA treatment. The results showed that E-ZPP at a cut-off level of more than 105 μmol/mol heme and TS at a level of less than 25% were more specific to confirm the status of functional iron deficiency in iron-overloaded patients. The two criterion values had the highest accuracy to predict a response to treatment. Conclusions Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 μmol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.

F. Chiurazzi - One of the best experts on this subject based on the ideXlab platform.

  • Clinical follow-up of 378 patients with autoimmune hemolytic anemia: prognostic impact of hemoglobin levels, autoantibody class, and reticulocytopenia at onset on the relapse risk and outcome
    2017
    Co-Authors: B. Fattizzo, A. Zaninoni, J. Giannotta, M. Lunghi, A. Ferrari, A.p. Leporace, N. Maschio, L. Scaramucci, S. Cantoni, F. Chiurazzi
    Abstract:

    Background:Autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening, due to autoantibody class/thermal amplitude, efficiency in activating complement, activity of the reticuloendothelial system, and efficacy of bone marrow compensatory response. Aims: Here we analysed predictors of first relapse, complications, and fatality in a large AIHA series. Methods: We retrospectively studied 378 patients (135m and 243 F, median age 61 yrs, range 19-100) from 10 sites, followed-up for 4.3 yrs (range 0.5- 27). Patients were classified in warm (w)AIHA (DAT positive for IgG and IgG+C), cold agglutinin disease, CAD (C), mixed (IgG+C with high titer cold agglutinins) and atypical (DAT-, IgA+, wIgM). Cases were also grouped in very severe (Hb<6 g/dl), severe (Hb 6-8 g/dl), moderate (Hb 8-10 g/dl) and mild (Hb>10 g/dl). LDH was expressed as fold increase upper the limit of normality (ULN), and Reticulocytes as absolute count and Reticulocyte Index. The following therapy lines were considered a) steroids +/-IvIg, b) rituximab c) splenectomy, d) immunosuppressive drugs (azathioprine, cyclophosphamyde, cyclosporin), and e) transfusions, plasma exchange, erythropoietinResults: Table 1 shows clinical and laboratory characteristics of AIHA cases at onset and distribution of thermal types. Hb values were significantly lower in IgG+C wAIHA and atypical cases (p<0.001), LDH higher in IgG+C wAIHA, mixed and atypical forms (p=0.01), and Hb and LDH values were negatively correlated (r= -0.25, p<0.001). Absolute Reticulocytes were reduced in CAD, mixed and IgG+C wAIHA (p<0.001) together with inadequate reticulocytosis (p=0.01). Moreover, the Reticulocyte Index was lower in cases with Hb<6 g/dL (65 vs 98, p<0.001), along with more frequent inadequate reticulocytosis (87 vs 70%, p=0.01). First line therapy was administered in almost all cases but 25 CAD. A second therapy line was mostly required in IgG+C wAIHA, mixed, and to a lesser extent in CAD (p=0.005). The ultra-refractory cases requiring 4 or more lines of therapy were mainly mixed, atypical and CAD. Considering anemia severity, patients with Hb<8 g/dL more frequently required treatment after first-line (51 vs 33%, p=0.004; p=0.03), or even 3 or more therapy lines (52/71, 73% vs 19/71, 26%, p<0.001). The following hazard ratios (HR) emerged from multivariate Cox regression analysis: HR 3.2 (95% CI 1.4-7), 2.9 (1.4-6.2), 3.4 (1.6-7.5), for Hb <6, 6-8, and 8-10 g/dL compared to patients with Hb >10, respectivelyAs regards complications, infections were observed in 14% of cases, mostly mixed AIHA (p=0.02); thrombosis occurred in 10% and acute renal failure in 3% of patients, with no relationship with AIHA type/Hb values. Evans\u2019 syndrome was more frequent in mixed or atypical cases (p=0.04) and in severe forms (74% with Hb<8 g/dL vs 26%, p=0.005), and was associated with higher relapse risk (HR 2.3, 95% CI 1.4-3.9). Seventy patients died during the followup, and 12 because of AIHA-related acute complications. Higher mortality was observed for infections (HR 5.8, 95% CI), acute renal failure (HR 7.6, 95% CI) and Evans\u2019 syndrome (HR 8.3, 95% CI).Summary/Conclusions: In conclusion, we found that severity of anemia at onset was the major determinant of relapse risk. The lowest Hb levels were observed in patients with IgG+C WAIHA and atypical cases along with higher LDH levels and inadequate reticulocytosis, advising strict clinical observation in these patient

  • Clinical follow-up of 378 patients with autoimmune hemolytic anemia: prognostic impact of hemoglobin levels, autoantibody class, and reticulocytopenia at onset on the relapse risk and outcome
    2017
    Co-Authors: B. Fattizzo, A. Zaninoni, J. Giannotta, M. Lunghi, A. Ferrari, A.p. Leporace, N. Maschio, L. Scaramucci, S. Cantoni, F. Chiurazzi
    Abstract:

    Autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening, due to autoantibody class/thermal amplitude and bone marrow compensatory response. Here we studied 378 patients (135 M and 243 F, median age 61 yrs, range 19-100), followed-up for 4.3 yrs (range 0.5-27), classified in warm (w)AIHA (DAT positive for IgG and IgG+C), cold agglutinin disease, CAD (C), mixed (IgG+C with high titer cold agglutinins) and atypical (DAT-, IgA+, wIgM). Anemia was categorized in Hb<6, 6-8, 8-10 and >10 g/dl, LDH expressed as fold upper the limit of normality (ULN) and Reticulocytes as absolute count and Index. The therapy lines were: steroids, rituximab, splenectomy, immunosuppressors, and transfusions/plasma exchange/erythropoietin. Hb was lower in IgG+C wAIHA and atypical cases (p<0.001), LDH higher in IgG+C wAIHA, mixed and atypical forms (p=0.01), and Hb and LDH values were negatively correlated (r=-0.25,p<0.001)[Table1]. Reticulocytes were lowerin CAD, mixed and IgG+C wAIHA (p<0.001) with inadequate reticulocytosis (p=0.01). Moreover, Reticulocyte Index was lower in cases with Hb<6 g/dL (p<0.001), with inadequate reticulocytosis (87 vs 70%,p=0.01).1st line therapy was administered in all cases but 25 CAD. 2nd line was mostly required in IgG+C wAIHA, mixed, and CAD (p=0.005). Ultra-refractory cases requiring 4 or> lines were mixed, atypical, and CAD. Patients with Hb<8 g/dL frequently required a 2nd line (51 vs 33%, p=0.004; p=0.03), or 3 or > lines (73% vs 26%, p<0.001). The following hazard ratios (HR) emerged from multivariate analysis: 3.2 (95% CI 1.4-7), 2.9 (1.4-6.2), 3.4 (1.6-7.5), for Hb<6, 6-8, and 8-10 g/dL compared to patients with Hb>10. Infections occurred in 14% of cases (mostly mixed AIHA, p=0.02), thrombosis in 10%, and acute renal failure (ARF) in 3% with no relationship with AIHA type/Hb. Evans\u2019 syndrome was frequent in mixed or atypical (p=0.04) and in severe forms (74% with Hb<8 g/dL vs 26%, p=0.005), and associated with higher relapse risk (HR 2.3, 95% CI 1.4-3.9). Seventy patients died, 12 because of AIHA complications. Mortality correlated with infections (HR 5.8),ARF (HR 7.6) and Evans\u2019 syndrome (HR 8.3). In conclusion, we found that anemia severity at onset was the major determinant of relapse risk. The lowest Hb levels were observed in patients with IgG+C WAIHA and atypical cases along with higher LDH levels and inadequate reticulocytosis, advising strict clinical observation in these patients