Low Levels of Serum Ferritin Lead to Adequate Hemoglobin Levels and Good Survival in Hemodialysis Patients

Abstract

Background: The optimal level of serum ferritin (s-ft) for anemia control and good survival in hemodialysis (HD) patients remains unclear. A 10-year survey was performed to clarify the appropriate quantities of s-ft and investigate the relationships among s-ft, transferrin saturation (TSAT), and mortality in HD patients. Methods: HD outpatients (n = 125) treated with erythropoiesis-stimulating agents (ESA) were followed for 10 years. The ESA and low-dose iron supplement dosages were adjusted to maintain the hemoglobin (Hb) at 10-11 g/dl, according to Japanese guidelines. The Kaplan-Meier method, log-rank tests, and the Cox proportional hazards model were used for performing the statistical analyses. The interactions among the Hb, s-ft, and TSAT were analyzed using a multiple linear regression model. Patients with TSAT ≥20% were classified according to the s-ft cutoff values: group 1 (s-ft <30 ng/ml); group 2 (s-ft 30-80 ng/ml); group 3 (s-ft >80 ng/ml); TSAT <20% was a predictor of poor outcome. Results: The survival rate in group 2 was significantly higher than that in other groups (p = 0.013), and the Cox proportional hazards model analysis showed a good effect of low levels of s-ft on patients' survival. The multiple linear regression model showed a strong effect of s-ft on the Hb (log [s-ft], β-coefficient −0.45: 95% confidence interval −0.65 to −0.26, p < 0.001). Conclusion: This study revealed that low levels of s-ft have a beneficial effect on the outcome of HD patients receiving ESA. Thus, the optimal s-ft level might be lower than that established previously for these patients.

Iatrogenic iron overload and its potential consequences in patients on hemodialysis

“…This MRI study suggests that the standard maximal monthly IV iron dose should be lowered to 250 mg to lessen the risk of iron overload in dialysis patients and seems to be in good agreement with the 3 recently published long-term epidemiological studies [12][13][14]87]. The worldwide nephrology community is also rediscovering the ingenious, cautious Japanese strategy of iron therapy, which maintains optimal hemoglobin levels (somewhat lower than in western countries) with minimal use of IV iron products and lower ferritin levels [21,88]. Rostoker et al have recently speculated that the better overall survival of Japanese hemodialysis patients, as compared with US and European patients, might be, at least in part, related to lower use of IV iron products and, thus, less iron overload although these findings may also be related to less inflammation (partially) due to a very high quality of dialysis in Japan [3].…”

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

“…The Japanese Society for Dialysis, out of concern for iron overload, proposed as early as 2011 that minimal IV iron (up to 650 mg in the induction phase) be given to hemodialysis patients and only in cases of true iron deficiency (ferritin < 100 μg/L), and also warned against maintenance IV iron therapy . This careful strategy of iron repletion allowed adequate hemoglobin levels with low ferritin, moderate transferrin saturation without any detrimental effect on survival and was again advocated this year for Japanese dialysis populations …”

Burden of Anemia in Chronic Kidney Disease Patients in Japan: A Literature Review

“…Data from a longitudinal study also revealed an association between increased mortality and lower baseline Hb levels (relative risk, 1.78, Hb <8 g/dL vs. Hb 11–11.99 g/dL) . Furthermore, among HD patients receiving ESA, those with lower baseline serum ferritin levels and TSAT >20% had a lower risk of death compared with those with higher baseline ferritin levels and TSAT ≤20% (HR, 0.16 [ P = 0.004], 95% CI 0.05─0.55, TSAT >20% [serum ferritin 30–80 ng/mL] vs. TSAT ≤20%) . Similarly, a study by Kuragano et al showed that among HD patients treated with ESA and iron over a 2‐year period, the risk of death was higher for those who had an upward trend from low to high ferritin (HR, 6.18; 95% CI 1.99─19.12) during the study period or with high‐amplitude fluctuations in ferritin levels (HR, 3.75; 95% CI 1.15─12.28) compared with those with low ferritin levels .…”

“…Although none of the 10 studies reporting mortality data evaluated mortality rate due to anemia in CKD, seven studies reported all‐cause mortality in HD patients. Mortality rate ranged from 7.2–13.3% in stage 5 CKD patients (time to endpoint, 18–25 months) to 35.2% in CKD patients on dialysis receiving ESA treatment to maintain 10≤ Hb <11 g/dL (time to endpoint, 10 years) . Okazaki et al reported that among HD patients, increased mortality was associated with ESA resistance (hazard ratio [HR], 4.204, highest [10.0–33.7] vs. lowest [2.0–5.0] erythropoietin resistance index [ERI] tertile; 95% CI 1.173–15.065) .…”