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Markers of iron status in chronic kidney disease.

ABSTRACT: Anemia is one of the main comorbidities related to chronic kidney disease (CKD). Until the advent of erythropoiesis stimulating agents (ESA), endogenous erythropoietin deficiency has been thought to be the main culprit of anemia in CKD patients. The use of ESAs has shed new light on the physiology of CKD anemia, where iron homeostasis plays an increasingly important role. Disorders of iron homeostasis occurring in CKD turn the anemia management in those patients into a complex multifactorial therapeutic task, where ESA and Iron dose must be properly balanced to achieve the desired outcome without exposing the patients to the risk of serious adverse events. This review covers diagnostic markers traditionally used for quantifying iron status in CKD patients, such as serum ferritin and transferrin saturation, new ones, such as reticulocyte hemoglobin content and percent hypochromic red cells (HRC), as well as experimental ones, such as hepcidin and soluble transferrin receptor (sTfR). Each marker is presented in terms of their diagnostic performance, followed by biological and analytical variability data. Advantages and disadvantages of each marker are briefly discussed. Although serum ferritin and transferrin saturation are easily available, they exhibit large biological variability and require caution when used for diagnosing iron status in CKD patients. Reticulocyte hemoglobin content and the percentage of HRC are more powerful, but their widespread use is hampered by the issue of sample stability in storage. sTfR and hepcidin show promise, but require further investigation as well as the development of standardized, low-cost assay platforms.

SUBMITTER: Gaweda AE

PROVIDER: S-EPMC6247786 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Markers of iron status in chronic kidney disease.

Gaweda Adam E AE

Hemodialysis international. International Symposium on Home Hemodialysis 20170322

Anemia is one of the main comorbidities related to chronic kidney disease (CKD). Until the advent of erythropoiesis stimulating agents (ESA), endogenous erythropoietin deficiency has been thought to be the main culprit of anemia in CKD patients. The use of ESAs has shed new light on the physiology of CKD anemia, where iron homeostasis plays an increasingly important role. Disorders of iron homeostasis occurring in CKD turn the anemia management in those patients into a complex multifactorial the ...[more]

PMID: 28328097

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Project description:Background: Even though it is well-known that iron deficiency is the result of chronic kidney disease (CKD), whether iron will affect kidney function and disease in the general population is not clear. We thus conducted a nationwide cross-sectional study using data from the China Health and Nutrition Survey (CHNS) to assess the relationship of iron status with estimated glomerular filtration rate (eGFR) and CKD among general adults. Methods: A total of 8,339 adults from the China Health and Nutrition Survey in the wave of 2009 were included to assess the association between iron status and eGFR/CKD. Serum ferritin (SF), transferrin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) were measured. The relationship of iron status and eGFR was evaluated by using multi-variable linear regression model. The effect of iron status on the odds of CKD was calculated by logistic regression model. Results: For the association between iron status and eGFR, every 100 ?g/L increase in SF was correlated with 0.26 ml/min per 1.73 m2 (95% CI: 0.08-0.44) decrease in eGFR, and every 5 mg/L increase in sTfR was associated with a decrease of 6.00 ml/min per 1.73 m2 (95% CI: 3.79-8.21) in eGFR. There were no significant associations between Hb or transferrin with eGFR. For the association between iron status and CKD, every 5 g/L increase in sTfR was associated with an odds ratio of 3.72 (95% CI: 2.16-6.13) for CKD. The concentrations of Hb were associated with the odds of CKD in a U-shaped manner, with the lowest risk in the Hb range of 136-141 g/L. There was a positive correlation between SF concentration and CKD prevalence but not in a dose-response manner. The odds of CKD for participants in the highest tertile increased by 28% (98% CI: 1-63%) compared with those in the lowest tertile. Conclusion: The concentration of SF and sTfR was positively correlated with the odds of CKD, and Hb was associated with the odds of CKD in a U-shaped manner. Further large prospective researches are warranted to confirm these findings.

Project description:Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study.

Project description:BackgroundChronic kidney disease-mineral and bone disorder (CKD-MBD) in dogs is associated with hypovitaminosis D, increased parathyroid hormone (PTH), and increased fibroblast growth factor-23 (FGF-23) concentrations. Best practice for vitamin D metabolite supplementation in CKD-MBD remains unknown.ObjectiveTo provide an extended-release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD-MBD.AnimalsTen dogs with International Renal Interest Society stages 2 and 3 CKD.MethodsIn a prospective study, dogs received a calcifediol supplement for 84 days. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), creatinine, calcium, phosphorus, PTH, plasma FGF-23 concentrations, and urine profiles were measured monthly during supplementation. Urine calcium to creatinine (UCa/Cr) ratios and fractional excretion of calcium, phosphorus, and sodium were determined.ResultsAll serum vitamin D metabolite concentrations increased significantly by day 84 (P < .001): [25(OH)D (median 249.9 ng/mL; range, 149.7-469.9 ng/mL) compared to baseline (median 50.2 ng/mL; range, 31.3-66.0 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 56.9-88.1 pg/mL) compared to baseline (median 37.3 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 81.4 ng/mL; range, 22.1-151.7 ng/mL) compared to baseline (median 15.4 ng/mL; range, 6.9-40.6 ng/mL)]. There were no significant differences in calcium, phosphorus, PTH concentrations, UCa/Cr or fractional excretion of calcium. No dog developed ionized hypercalcemia. Plasma FGF-23 concentrations increased by day 84 (median 1219 pg/mL; range, 229-8824 pg/mL) compared to baseline (median 798 pg/mL; range, 103-4.145 pg/mL) (P < .01).Conclusions and clinical importanceCalcifediol supplementation for 84 days was well-tolerated in dogs with IRIS stages 2 and 3 CKD. It remains to be determined how long-term supplementation would affect CKD progression and QOL.

Project description:Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD.This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ?40 mL/min), hemoglobin 11-12 g/dL and iron deficiency (ferritin <100 ?g/L or transferrin saturation <20%), who were regularly treated with oral iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study.Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 ?g/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study.Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study.ClinicalTrials.gov NCT02232906.

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Markers of iron status in chronic kidney disease.

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Markers of iron status in chronic kidney disease.

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