Combined High Serum Ferritin and Low Iron Saturation in Hemodialysis Patients

Abstract

Background: Serum ferritin, frequently used as a marker of iron status in individuals with chronic kidney disease, is also an inflammatory marker. The concurrent combination of high serum ferritin and low iron saturation ratio (ISAT) usually poses a diagnostic dilemma. We hypothesized that serum ferritin >500 ng/ml, especially in the seemingly paradoxical presence of ISAT level <25%, is more strongly associated with inflammation than with iron in maintenance hemodialysis (MHD) patients.Design, setting, and participants: In 789 MHD patients in the Los Angeles area, the association of serum ferritin >500 ng/ml with inflammatory markers, including IL-6 (IL-6) and C-reactive protein levels, and malnutrition-inflammation score (MIS) was examined.Results: After multivariate adjustment for case-mix and other measures of malnutrition-inflammation complex, MHD patients with serum ferritin >500 ng/ml and ISAT <25% had higher odds ratio for serum C-reactive protein >10 mg/L. The area under the receiver operating characteristic curves for the continuum of ISAT and IL-6 in detecting a serum ferritin >500 ng/ml were identical (0.57 versus 0.56, P ‫؍‬ 0.7). The combination of IL-6 with ISAT yielded a higher area under the receiver operating characteristic curve (0.61) than either ISAT or IL-6 alone (P ‫؍‬ 0.03 and P ‫؍‬ 0.02, respectively).Conclusion: In MHD patients, ferritin values above 500 ng/ml, especially in paradoxical conjunction with low ISAT, are associated with inflammation. Strategies to dissociate inflammation from iron metabolism to mitigate the confounding impact of inflammation on iron and to improve iron treatment responsiveness may improve anemia management in chronic kidney disease.

Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis

“…As result of this regulation, iron absorption is restricted when iron stores are sufficient and increased when iron stores are deficient. 33 Our results showing the plateau (18) 609 (26) 899 (31) 628 (31) 858 ( Hemoglobin (g/dl) 11.61 (0.08) 11.71 (0.11) 11.42 (0.10) 11.14 (0.12) 11.20 (10.50-12.10) 11.00 (10.25-12.30) (27) 578 (38) 453 (23) 432 (29) 350 ( A last follow-up observation with carried forward imputation was used to impute missing values for all laboratory outcomes. Sample sizes for the 52-week active control period ranged from 247 to 281 patients for the different outcomes in the ferric citrate group and from 132 to 146 patients in the active control group.…”

“…It is unlikely that the increases in serum ferritin were related to inflammation, because TSAT also increased, and subjects on ferric citrate had evidence of less inflammation, such as fewer infection-associated SAEs, than subjects on active control. 27 We did not compare the ferric citrate group with a control group with no iv iron administration and hence, cannot comment on its performance as a standalone iron therapy.…”

Pathophysiology of anemia in chronic kidney diseases: A review

“…In the laboratory, this condition is confirmed by increased SF concentrations, and reduced pFe, transferrin levels, and TSAT (ref. 45,46 ). In patients with renal disease, reduced intravascular survival of red blood cells is caused by chronic hemolysis, which is the result of accumulation of hypothetical uremic toxins in the blood.…”

Novel Lipoprotein Subfraction and Size Measurements in Prediction of Mortality in Maintenance Hemodialysis Patients

“…Circulating IL-6 and TNF-␣ cytokines were measured with immunoassay kits (R&D Systems, Minneapolis, MN; units: pg/ml; normal range: IL-6 Ͻ 9.9 pg/ml, TNF-␣ Ͻ 4.7 pg/ml). CRP and the cytokines were measured in the General Clinical Research Center Laboratories of Harbor-UCLA (22). Total homocysteine was determined by high-performance liquid chromatography, and serum transthyretin (prealbumin) was determined by immunoprecipitation analysis (23).…”