Impact of Transferrin Saturation on All-Cause Mortality in Patients on Maintenance Hemodialysis

2019 ◽  
Vol 48 (2) ◽  
pp. 158-166
Author(s):  
Madoka Sato ◽  
Norio Hanafusa ◽  
Ken Tsuchiya ◽  
Hiroshi Kawaguchi ◽  
Kosaku Nitta

Background: Transferrin saturation (TSAT) is an index that represents the iron-binding capacity of transferrin, which is the main transport protein for iron, and is widely used to evaluate iron status. Objective: To evaluate the prognostic importance of TSAT in Japanese patients on maintenance hemodialysis (MHD). Methods: A total of 398 patients on MHD were recruited and divided into 3 groups on the basis of their baseline TSAT levels (<20, 20–40, and >40%). Results: There was no difference in the proportion of patients on erythropoiesis-stimulating agents or iron supplements between the 3 groups. During a mean follow-up period of 52.2 ± 1 6.3 months, 130 patients died of cardiovascular causes (n = 63, 15.8%) or infection (n = 47, 11.8%). Compared with the reference group (TSAT 20–40%), patients with a TSAT <20% had a significantly higher all-cause mortality rate (6.44 vs. 9.55 events per 100 patient-years, p = 0.0452). Kaplan-Meier analysis showed that all-cause mortality rate was significantly higher in patients with TSAT <20% than in the other 2 groups (p = 0.0353). Conclusions: Low TSAT was a significant independent risk factor for all-cause mortality in a cohort of Japanese patients on MHD. The findings of this study suggest that the adverse clinical outcomes in patients with low TSAT can be partly attributed to infection-related iron deficiency.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pei-Hua Yu ◽  
Ming-Yen Lin ◽  
Yi-Wen Chiu ◽  
Jia-Jung Lee ◽  
Shang-Jyh Hwang ◽  
...  

AbstractLow transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both “normal TSAT low iron” and “low TSAT low iron” groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13–2.16 and OR 2.36; 95% CI 1.76–3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00–2.83 and OR 1.94; 95% CI 1.11–3.40, respectively). In conclusion, CKD stage 1–4 patients with normal TSAT but low serum iron are still at risk for anemia.


2008 ◽  
Vol 11 (7) ◽  
pp. 737-746 ◽  
Author(s):  
Halimatou Alaofè ◽  
John Zee ◽  
Romain Dossa ◽  
Huguette Turgeon O’Brien

AbstractIron deficiency (ID) is the most prevalent micronutrient deficiency in the world, particularly in developing countries. Blood samples and a qualitative FFQ on Fe- and vitamin C-rich foods were obtained in 180 adolescent girls aged 12 to 17 years living in two boarding schools from south Benin. ID, defined as serum ferritin either <20μg/l or 20–50μg/l, plus two of the following parameters: serum Fe<11μmol/l, total iron-binding capacity>73μmol/l or transferrin saturation<20%, was found in 32% of subjects. Anaemia (Hb<120g/l) was found in 51% of adolescents, while 24% suffered from iron-deficiency anaemia (IDA) (ID and Hb<20g/l). After adjusting for confounding factors (age, mother's and father's occupation, household size) in a logistic regression equation, subjects having a low meat consumption (beef, mutton, pork) (<4 times/week) were more than twice as likely to suffer from ID (OR=2·43; 95% CI 1·72, 3·35;P=0·04). Adolescents consuming less fruits (<4 times/week) also had a higher likelihood of suffering from ID (OR=1·53; 95% CI 1·31, 2·80;P=0·03). Finally, subjects whose meat consumption was low were twice as likely to suffer from IDA (OR=2·24; 95% CI 1·01, 4·96;P=0·04). The prevalence of ID represents an important health problem in these Beninese adolescent girls. A higher consumption of Fe-rich foods and of promoters of Fe absorption (meat factor and vitamin C) is recommended to prevent ID deficiency in these subjects.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5382-5382
Author(s):  
Rodolfo D Cancado ◽  
Paulo CJL Santos ◽  
Samuel Rostelato ◽  
Cristiane T Terada ◽  
Iris Gonzales ◽  
...  

Abstract Hereditary hemochromatosis (HH) is a disorder characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body. This iron overload has been associated with mutations in HFE gene (C282Y, H63D and S65C) and other genes. The objectives of this study were to assess the frequencies of functional mutations in HFE and TFR2 genes and to investigate their relationship with the iron status in a sample of blood donors. Blood donors (n=542) were recruited at the Hemocenter of the Santa Casa Hospital, Sao Paulo, Brazil. The genotypes for HFE (C282Y, H63D and S65C) TFR2 (Y250X and Q690P) gene mutations were evaluated by PCR-RFLP. The concentrations of serum iron and total iron-binding capacity (TIBC) were measured by automation system Advia®(Bayer Diagnostics) and serum ferritin by Axsym System®(Abbott Laboratories). The frequencies of HFE 282Y, HFE 63D and HFE 65C alleles were 2.1, 13.6 and 0.6%, respectively. The frequency C282Y allele (2.1%) in Brazilian blood donors is lower than that observed in blood donors from Northern Europe (5.1 to 8.2%, P&lt;0.05). The TFR2 250X and TFR2 690P alleles were not found in these subjects. The iron status was similar between HFE genotypes in women. However, men carrying HFE 282CY genotype had higher serum ferritin and lower TIBC concentrations when compared to the HFE 282CC genotype carriers. HFE 282CY genotype was also associated with higher transferrin saturation in men who donated blood at the first time. Moreover, male donors with HFE 63DD plus 63HD genotypes had higher serum iron and transferrin saturation when compared to those with HFE 63HH genotype. A relationship between HFE CY/HH/SS haplotype and lower TIBC concentrations was also found in men. The HFE 282Y and HFE 65C alleles were rare while the HFE 63D was frequent in blood donors. The mutations in TFR2 gene were not found in this study. The HFE 282Y and HFE 63D alleles were associated with alterations on iron status only in male blood donors.


Author(s):  
Neda Milinković

Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated in the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxy- and oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and the percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached a significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5150-5150
Author(s):  
R. Kurzrock ◽  
E. Angévin ◽  
S. Cohen ◽  
J. Van Laethem ◽  
B. Rijnbeek ◽  
...  

Abstract Abstract 5150 Introduction: Siltuximab is a chimeric monoclonal antibody with high affinity for the inflammatory cytokine, IL-6, which is currently being studied in hematologic, solid malignancies and multicentric Castleman's disease (MCD). In addition to representing a therapeutic target, IL-6 is reported to play a key role in the etiology and symptoms of anemia of cancer. A possible mechanism is through up-regulation of hepatic production of hepcidin, the central iron-regulatory hormone. Siltuximab treatment has previously been shown to be associated with clinically significant Hb increases in MCD (a disorder caused by deregulated IL-6 production) and renal cell carcinoma. We have prospectively studied the Hb response in the context of a phase I study with siltuximab in patients with advanced solid tumors. Patients and Methods Siltuximab was administered intravenously to patients with any advanced solid tumor at increasing dose levels (2.8 or 5.5 mg/kg every 2 weeks, 11 or 15 mg/kg every 3 weeks). Hepcidin (C-ELISA), Hb, CRP (marker for inflammation) and iron status (serum iron, ferritin, transferrin saturation, total iron binding capacity) were measured at baseline and serially during treatment. IL-6 was not measured since interference of the drug with assay performance prevents accurate measurement of bioactive IL-6. The relationships between these biomarkers and Hb response (defined as a maximum Hb increase of ≥1 g/dL during treatment) were evaluated. Results: Forty-four pts (18 colorectal, 12 ovarian, 5 pancreatic, 9 other) received a median of 3 siltuximab cycles (range 1 – 25). Eight patients were excluded from analysis because they received blood transfusions or ESAs. There were no objective tumor responses (CR or PR). Baseline Hb ranged from 9.4–15.3 g/dL (median 12.2). All 36 evaluable patients had an increase in Hb (median 1.35 g/dL; range 0.1–3.2). Eleven (31%) patients had a maximum increase of ≥2 g/dL. Maximum Hb levels did not exceed the upper limit of normal. Baseline hepcidin (median 118.6 ng/mL; range 9.5–493.3) was positively correlated with baseline CRP (median 13.6 mg/L; range 0.42–152.0) (p<0.05) and ferritin (median 346 pmol/L; range 74.2–8543.1) (p<0.05) but not with baseline Hb or Hb response. For subjects with a Hb response of more than 2 g/dL an association was found with Day 8 hepcidin (p = 0.03) when controlled for baseline serum iron. Early hepcidin percentage change was not correlated with Hb response. Conclusion: Siltuximab treatment was associated with clinically meaningful Hb response in this moderately anemic refractory cancer population. The exact mechanism of action remains uncertain, however correlation with additional markers (e.g., soluble transferrin receptor, inflammatory markers such as IL-6) might also be important to identify patients most likely to respond to treatment and should be evaluated further in randomized trials. Disclosures: Kurzrock: Johnson & Johnson: Research Funding. Angévin:Johnson & Johnson: Research Funding. Cohen:Johnson & Johnson: Research Funding. Van Laethem:Johnson & Johnson: Research Funding. Rijnbeek:Johnson & Johnson: Employment. Vermeulen:Johnson & Johnson: Employment. Tromp:Johnson & Johnson: Employment. Li:Johnson & Johnson: Employment. Reddy:Johnson & Johnson: Employment. Cornfeld:Johnson & Johnson: Employment. Tabernero:Johnson & Johnson: Research Funding.


2017 ◽  
Vol 44 (3) ◽  
pp. 380-387 ◽  
Author(s):  
Eunjeong Kang ◽  
Seung-sik Hwang ◽  
Dong Ki Kim ◽  
Kook-Hwan Oh ◽  
Kwon Wook Joo ◽  
...  

Objective.To explain the clinical effect of serum uric acid (SUA) levels as a risk factor for mortality, considering exclusion of kidney function.Methods.Participants aged over 40 years who underwent health checkups were recruited. Individuals with estimated glomerular filtrations rates < 60 ml/min/1.73 m2 and who received laboratory study and colonoscopy on the same day were excluded.Results.SUA levels were higher in men than in women (5.7 ± 1.2 mg/dl for men and 4.2 ± 0.9 mg/dl for women, p < 0.001). During 12.3 ± 3.6 years of followup, 1402 deaths occurred among 27,490 participants. About 6.9% of men and 3.1% of women died. The overall mortality rate had a U-shaped association with SUA levels, a U-shaped association in men, and no association in women. There was a significant interaction of sex for the SUA-mortality association (p for interaction = 0.049); therefore, survival analysis was conducted by sex. In men, the lower SUA group had a higher mortality rate after adjustment (SUA ≤ 4.0 mg/dl, adjusted HR 1.413, 95% CI 1.158–1.724, p = 0.001) compared with the reference group (SUA 4.1–6.0 mg/dl). A higher SUA contributed to an insignificant increased mortality in men (> 8.0 mg/dl, adjusted HR 1.140, 95% CI 0.794–1.636, p = 0.479). Women failed to show any significant association between SUA and mortality.Conclusion.This study provided novel evidence that SUA-mortality association differed by sex. We demonstrated that a lower SUA was an independent risk factor for all-cause mortality in men with normal kidney function.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Zhe Wang

Abstract Background and Aims Vascular calcification is the risk factor for cardiovascular event, cardiovascular mortality and all-cause mortality in maintenance hemodialysis (MHD) patients. We investigated the effects of abdominal aortic calcification (AAC) progression on outcomes in MHD patients. Method 111 patients who were on MHD between Jun. 2014 and Oct. 2014 in the dialysis center and finished the AAC examination at baseline and two years later were included prospectively. We evaluated the progression of AAC by AAC score (AACs) at baseline and two years later. According to the change of AACs, the patients were divided into rapid AAC progression group (change of AACs&gt;median) and non-rapid AAC progression group (change of AACs≤median). We investigated the effects of AAC progression on outcomes in MHD patients in the follow-up period. Kaplan-Meier analysis was used to compare their survival rate. Uni- and multivariable Cox proportional hazard regression models were used to determine the risk factors of all-cause mortality, cardiovascular mortality and cardiovascular events. Results The presence of AAC was 78.4% (87/111), rapid AAC progression was seen in 54 patients, and non-rapid AAC progression was seen in 57 patients. The mean follow-up duration was 27.9(27.1, 28.0) months. Kaplan-Meier analysis showed that patients in rapid AAC progression group had a higher risk of mortality as compared to patients in non-rapid AAC progression group (P=0.017). Multivariate Cox regression analysis demonstrated that high baseline AACs (HR=1.135, 95%CI∼1.001∼1.286, P=0.048), hypoproteinemia (HR=0.789, 95%CI 0.640∼0.972, P=0.026) were independent risk factors for all-cause mortality. High baseline AACs (HR=1.187, 95%CI 1.038∼1.356, P=0.012), low spKt/V (HR=0.103, 95%CI 0.013∼0.801, P=0.030) were independent risk factors for cardiovascular mortality. Low spKt/V (HR=0.018, 95%CI 0.003∼0.115, P=0.000), hypoproteinemia (HR=0.736, 95%CI 0.608∼0.890, P=0.002) were independent risk factors for cardiovascular events. Conclusion Abdominal aortic calcification progression may increase the risk of cardiovascular events and death in MHD patients. Severity of abdominal aortic calcification, adequacy of dialysis, and nutritional status are predictors of outcomes in MHD patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Li-xia Yu ◽  
Qi-feng Liu ◽  
Jian-hua Feng ◽  
Sha-sha Li ◽  
Xiao-xia Gu ◽  
...  

Background. The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. Materials. A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. Results. During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006 ), all-cause mortality (28.4% vs. 11.6%, p = 0.003 ), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001 ). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030–3.661), p = 0.040 )], all-cause mortality [2.073 (1.023–4.203), p = 0.043 ], and combined adverse outcomes [1.818 (1.092–3.026), p = 0.021 ] in fully adjusted models. Conclusions. The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.


2019 ◽  
Vol 14 (6) ◽  
pp. 873-881 ◽  
Author(s):  
Tsuyoshi Ohnishi ◽  
Miho Kimachi ◽  
Shingo Fukuma ◽  
Tadao Akizawa ◽  
Shunichi Fukuhara

Background and objectivesAlmost half of patients on dialysis demonstrate a postdialysis serum potassium ≤3.5 mEq/L. We aimed to examine the relationship between postdialysis potassium levels and all-cause mortality.Design, setting, patients, & measurementsWe conducted a cohort study of 3967 participants on maintenance hemodialysis from the Dialysis Outcomes and Practice Patterns Study in Japan (2009–2012 and 2012–2015). Postdialysis serum potassium was measured repeatedly at 4-month intervals and used as a time-varying variable. We estimated the hazard ratio of all-cause mortality rate using Cox hazard regression models, with and without adjusting for time-varying predialysis serum potassium. Models were adjusted for baseline characteristics and time-varying laboratory parameters. We also analyzed associations of combinations of pre- and postdialysis potassium with mortality.ResultsThe age of participants at baseline was 65±12 years (mean±SD), 2552 (64%) were men, and 96% were treated with a dialysate potassium level of 2.0 to <2.5 mEq/L. The median follow-up period was 2.6 (interquartile range, 1.3–2.8) years. During the follow-up period, 562 (14%) of 3967 participants died, and the overall mortality rate was 6.7 per 100 person-years. Compared with postdialysis potassium of 3.0 to <3.5 mEq/L, the hazard ratios of postdialysis hypokalemia (<3.0 mEq/L) were 1.84 (95% confidence interval, 1.44 to 2.34) in the unadjusted model, 1.44 (95% confidence interval, 1.14 to 1.82) in the model without adjusting for predialysis serum potassium, and 1.10 (95% confidence interval, 0.84 to 1.44) in the model adjusted for predialysis serum potassium. The combination of pre- and postdialysis hypokalemia was associated with the highest mortality risk (hazard ratio, 1.72; 95% confidence interval, 1.35 to 2.19, reference; pre- and postdialysis nonhypokalemia).ConclusionsPostdialysis hypokalemia was associated with mortality, but this association was not independent of predialysis potassium.


Author(s):  
Febrina Rovani ◽  
Asvin Nurulita ◽  
Mansyur Arif

Anemia, the common feature of Chronic Kidney Disease (CKD), is a multifactorial process due to disordered erythropoiesis and iron homeostasis. Determining the cause of anemia is important for adequate management. A bone marrow biopsy using Prussian Blue as the gold standard for diagnosis is invasive and more complicated to perform. Reticulocytes-Hemoglobin (Ret-He) a new parameter that indicates the hemoglobin content in reticulocytes is faster, easier, and less expensive. This study aimed to analyze the Ret-He in determining the iron status in patients with CKD. A cross-sectional study was held in the Clinical Pathology Laboratory of Dr. Wahidin Sudirohusodo Hospital Makassar during April-August 2016. Forty-five (45) samples were tested for iron serum (Fe), Total Iron Binding Capacity (TIBC), and Complete Blood Count (CBC) ordered by the physician. Reticulocytes-Hemoglobin was tested using the whole blood. Subjects were around the age of 19-71 years, no significant difference was found between numbers of males and females (46.6% and 53.3%). Hemoglobin median was 8 (5.0-15) g/dL, Fe 50 (6-177) U/mL, TIBC 183 (73-379), Transferrin Saturation (Tsat) 25 (5-95)%. Spearman correlation test method showed significant correlations between Ret-He and iron serum r=0.533, p <0.001, Ret-He and TIBC r=0.321 p=0.031 Ret-He and transferrin saturation r=0.416 p=0.019. The Mann-Whitney method showed no significant difference of Ret-He in both groups (Tsat <20% and >20%). There were significant correlations between Ret-He and iron, Ret-He and TIBC, Ret-He and transferrin saturation. A further study using larger samples is suggested to consider factors affecting the result of Ret-He.


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