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Biomedical subjects

Der-Cherng Tarng

Publications and source records attributed to Der-Cherng Tarng.

16 recordsLinked to original sources
PubMed2006

Association between transferrin receptor-ferritin index and conventional measures of iron responsiveness in hemodialysis patients.

BACKGROUND: The diagnostic power of the transferrin receptor-ferritin (TfR-F) index for identification of iron responsiveness in long-term hemodialysis (HD) patients compared with the routine markers recommended by the current US and European guidelines was appraised. METHODS: Initially, 121 long-term HD patients with a serum ferritin level less than 800 microg/L and on recombinant erythropoietin (rHuEPO) therapy for longer than 6 months were enrolled for intravenous iron (IVFE) supplementation (100 mg of iron polymaltose 3 times/wk for 4 weeks, then 100 mg every 2 weeks for 5 months). Routine iron tests (ie, serum ferritin and transferrin saturation [TSAT]), TfR-F index calculated by the ratio of soluble TfR to log ferritin level, hematocrit, hemoglobin, red blood cell count, and serum high-sensitive C-reactive protein were examined at baseline. Hematocrit and hemoglobin were followed up every 2 weeks during the study period. RESULTS: One hundred patients (52 men, 48 women; mean age, 59 years) completed this study. Fifty-two patients were IVFE responders, defined as an increase in hematocrit greater than 3% and/or a decrease in rHuEPO dose greater than 30% of baseline values at the end of the study, and 48 nonresponders did not fulfill these criteria. Of 52 responders, only 14 patients (27%) could be recognized for iron deficiency by means of routine iron tests (ferritin < 100 microg/L and/or TSAT < 20%). Thirty-three responders (63%) could be further identified for iron deficiency by using TfR-F index (> 0.6), but 5 (10%) still could not by either method. Analyses by using receiver operating characteristic (ROC) curves showed that a cutoff value greater than 0.6 for TfR-F index had greater sensitivity (90%) for the detection of iron deficiency than ferritin level less than 100 microg/L (29%) and TSAT less than 20% (6%). TfR-F index showed a greater area under the ROC curve than ferritin level (P < 0.05) and TSAT (P < 0.001). CONCLUSION: TfR-F index is superior to routine tests for predicting response to IVFE supplementation in long-term HD patients. Our study indicates that TfR-F index is a new and surrogate marker to estimate body iron stores and guide IVFE therapy for long-term HD patients.

Adult↗
PubMed2005

High-calorie supplementation increases serum leptin levels and improves response to rHuEPO in long-term hemodialysis patients.

BACKGROUND: Dialysis patients with a high body mass index are less likely to experience severe anemia. Leptin, a hormone secreted by adipocytes, may have a role in protecting against renal anemia. The aim of the present study is to determine the effect of an increase in serum leptin levels by increasing energy intake on recombinant human erythropoietin (rHuEPO) response in long-term hemodialysis (HD) patients. METHODS: We enrolled 65 long-term HD patients to explore the association between leptin level and rHuEPO response by classifying them as either high- or low-leptin individuals (phase 1). Thereafter, 39 patients with malnutrition by means of Subjective Global Assessment were randomly assigned to high-energy and high-protein (an extra 475 kcal and 16.6 g of protein daily; group A; n = 12) or standard-energy, but high-protein (an extra 67.2 kcal and 16.8 g of protein daily; group B; n = 27), supplementation for 12 weeks. Serial serum leptin levels, nutritional measures, and hematologic parameters were obtained. Age- and sex-matched well-nourished patients (group C; n = 16) not administered extra nutritional supplementation served as control subjects (phase 2). RESULTS: In phase 1, a significantly lower erythropoietin dose, greater hematocrit, and better nutritional measures were observed in the high-leptin group (P < 0.001). In phase 2, there was a significant increase in body fat mass (P = 0.001) and median serum leptin levels (P < 0.001) in response to 12 weeks of high-energy supplementation in group A, accompanied by markedly improved erythropoiesis (P < 0.05) compared with groups B and C. CONCLUSION: Hyperleptinemia reflects better nutritional status and rHuEPO response in long-term HD patients. Increasing energy intake improves erythropoiesis, which may be mediated in part by an increase in serum leptin levels.

Adipose Tissue↗
PubMed2004

Effect of intravenous ascorbic acid medication on serum levels of soluble transferrin receptor in hemodialysis patients.

Intravenous ascorbic acid (IVAA) medication has been shown to facilitate iron release from inert depots and subsequently circumvent the defective iron utilization in chronic hemodialysis (HD) patients who are treated with recombinant human erythropoietin (rHuEPO). This study focuses on the effects of IVAA supplementation on serum concentrations of soluble transferrin receptors (TfR) on the basis of the hypothesis that an increase of labile iron in the cytosol will lead to inhibition of TfR expression. First, 138 HD patients were studied to evaluate the interrelation between serum TfR and iron status. In a stepwise multivariate analysis, serum EPO and transferrin saturation (TSAT) were the two independent predictors for serum TfR in HD patients (r(2) = 0.510, P < 0.001). Further analyses showed that the lower the serum EPO and the higher the TSAT, the lower the serum TfR in HD patients who are on maintenance rHuEPO treatment. Second, 36 HD patients were recruited in a randomized, controlled study to receive IVAA (total dose of 2000 mg) or normal saline (placebo) medication. Serum levels of TfR, EPO, and ferritin and TSAT were measured at baseline and within 7 d after starting IVAA or placebo. There were no significant changes in serum EPO and ferritin levels in patients who received either IVAA (n = 18) or placebo (n = 18). Serum TfR levels (P < 0.001) significantly declined with a parallel rise in TSAT (P < 0.05) as compared with presupplemental values within 7 d in IVAA patients before any apparent alteration in hematocrit values, but the changes were not observed in the placebo group. The trend of decreased serum TfR and increased TSAT was similar in IVAA patients with ferritin of <500 microg/L or >500 microg/L. It is concluded that ascorbic acid status can significantly decrease serum TfR concentrations and increase percentage of TSAT, probably through alterations in intracellular iron metabolism.

Ascorbic Acid↗
PubMed2004

Protective effect of vitamin C on 8-hydroxy-2'-deoxyguanosine level in peripheral blood lymphocytes of chronic hemodialysis patients.

BACKGROUND: This study focused on the effect of vitamin C on the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level of cellular DNA, as well as 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MutT homologue (hMTH1) gene expression in peripheral blood lymphocytes of chronic hemodialysis patients. METHODS: Sixty chronic hemodialysis patients (35 men and 25 women) were recruited to participate in a randomized, placebo-controlled study. Treatment order is block-randomized with intravenous sodium ascorbate (vitamin C, 300 mg) or placebo (0.9% saline), administered postdialysis three times a week. We evaluated 8-OHdG level, intracellular reactive oxygen species (ROS) production, and gene expression of hOGG1 and hMTH1 in peripheral blood lymphocytes by using high-performance liquid chromatography (HPLC) electrochemical detection method, flow cytometric analysis, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: A total of 51 patients completed the study (26 in placebo group and 25 in vitamin C group). Mean 8-OHdG levels significantly decreased in total subjects following 8 weeks of vitamin C supplementation (22.9 vs. 18.8/10(6) dG, P < 0.01). The decrease in 8-OHdG levels after vitamin C supplementation was also noted in the patients with ferritin <500 or > or =500 microg/L and transferrin saturation (TSAT) <50 or > or =50% (P < 0.05). But 8-OHdG levels had no significant changes in total patients or in the four subgroups of patients treated with placebo as compared to their baselines. Intracellular ROS production by lymphocytes from the four subgroups of patients, either spontaneous (P < 0.05) or phorbol-12-myristate-13-acetate (PMA)-stimulated (P < 0.001), was significantly reduced after 8 weeks vitamin C supplementation. Steady-state hOGG1 mRNA levels were significantly up-regulated at 24 hours after vitamin C administration (P < 0.05), but hMTH1 mRNA levels were not. The changes in the spontaneous and PMA-stimulated ROS production, and an up-regulation of hOGG1 mRNA expression were not observed in patients treated with placebo as compared to their baselines. CONCLUSION: Vitamin C supplementation in chronic hemodialysis patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS production, as well as up-regulate hOGG1 gene expression for repair. There is no compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte DNA base oxidation, even in the status of increased iron stores.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Acquired fanconi syndrome induced by mixed Chinese herbs presenting as proximal muscle weakness.

We report a rare case with acquired Fanconi syndrome caused by mixed Chinese herbs, initially presenting as waddling gait and lower limb muscle atrophy. From a series of investigations, proximal renal tubule injury with functional defects and Chinese herb nephropathy were discovered. Hypophosphatemic osteomalacia and type II muscle fiber atrophy shown in muscle biopsy of left quadriceps may be associated with the sequelae of ingestion of mixed crude Chinese herbs. Aggressive and early alkali treatment with supplementation of phosphate and Vitamin D restored the patient's metabolic and musculoskeletal abnormalities.

Adult↗
PubMed2003

Early prediction of response to intravenous iron supplementation by reticulocyte haemoglobin content and high-fluorescence reticulocyte count in haemodialysis patients.

BACKGROUND: Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo. METHODS: Sixty-five HD patients with a serum ferritin level of <500 microg/l and on rHuEpo therapy for >6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of >3% and/or a reduction in rHuEpo dose of >30% over the baseline values at the end of the study. RESULTS: Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P<0.001). This paralleled a statistically significant rise in CHr and HFR (P<0.001). Univariate analyses showed that ferritin (P<0.010) and CHr (P<0.001) at baseline, changes in CHr (DeltaCHr(2W), P<0.001) and HFR (DeltaHFR(2W), P<0.010) at 2 weeks, as well as changes in CHr (DeltaCHr(4W), P<0.001) and HFR (DeltaHFR(4W), P<0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that DeltaCHr(4W) in conjunction with DeltaHFR(4W) exhibited an r(2) value of 0.531 (P<0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that DeltaCHr(4W) at a cut-off value of >1.2 pg and DeltaHFR(4W) of >500/microl were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response to IVFE therapy, with a sensitivity of 96% and a specificity of 100%. CONCLUSIONS: Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect iron-deficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.

Anemia, Iron-Deficiency↗
PubMed2002

Hypercalcemia in a renal transplant recipient suffering with Pneumocystis carinii pneumonia.

Hypercalcemia occurs frequently after renal transplantation. Preexisting hyperparathyroidism is the most common cause of post-transplantation hypercalcemia. We describe a renal transplant recipient infected with Pneumocystis carinii pneumonia (PCP) who developed hypercalcemia, elevated 1,25-dihydroxyvitamin D, and suppressed parathyroid hormone levels. This phenomenon mimics the extrarenal production of 1,25-dihydroxyvitamin D by activated alveolar macrophages in granulomatous diseases with hypercalcemia. To the best of our knowledge, this is the first report of 1,25-dihydroxyvitamin D-mediated hypercalcemia caused by PCP in a renal transplant recipient. This entity should be included in the differential diagnosis for renal transplant recipients with hypercalcemia, especially in patients who develop lung infections.

Diagnosis, Differential↗
PubMed2002

Determinants of circulating soluble transferrin receptor level in chronic haemodialysis patients.

BACKGROUND: The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTfR) 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 sTfR. HD patients received constant rHuEpo doses and basal sEpo was measured > or = 86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log(10)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 sTfR, sEpo, and reticulocyte index. Univariate analyses showed that the sTfR level strongly correlated with sEpo (r=0.60, P<0.001) and % HRC (r=0.60, P<0.001), and significantly with serum ferritin (r=-0.29, P<0.01), TS (r=-0.27, P<0.05), and dose of rHuEpo administered (r=0.27, P<0.05) in HD patients. sTfR also had a positive correlation with haematocrit (r=0.26, P<0.05), red blood cell (RBC) count (r=0.23, P<0.05), and reticulocyte count (r=0.24, P<0.05), but not with CRP (r=0.16, P>0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTfR level. Overall, the model explained 58.8% of the variability in sTfR (R(2)=0.588, P<0.001). CONCLUSIONS: Circulating sTfR 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 sTfR levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.

Biomarkers↗
PubMed2002

Increased oxidative damage to peripheral blood leukocyte DNA in chronic peritoneal dialysis patients.

This study focuses on the extent of oxidative DNA damage in peripheral blood leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'-deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an HPLC-electrochemical detection method in 24 age- and sex-matched healthy subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD patients. Mean 8-OHdG content was the highest in CPD patients, followed by the nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus 8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8-OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha-tocopherol and whole-blood reduced glutathione, and the higher levels of whole-blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05). Mean serum ferritin and iron levels and transferrin saturation were higher in the CPD patients than those in the nondialyzed patients and controls (ANOVA P < 0.05). Flow cytometric analyses of intracellular reactive oxygen species production of peripheral leukocytes showed that spontaneous production by granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production by granulocytes, lymphocytes and monocytes, were the highest from CPD patients, followed by nondialyzed patients, and then by the healthy subjects (ANOVA P < 0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment, spontaneous and PMA-induced reactive oxygen species production in leukocytes, and serum iron were the independent determinants of peripheral leukocyte 8-OHdG content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG levels in peripheral leukocyte DNA occur in the course of chronic renal failure, gradually increase with its progression, and are further exacerbated by PD treatment.

8-Hydroxy-2'-Deoxyguanosine↗