Review

Management of in

Supervisor : VS 宋志建 Presenter : PGY2 王宇凡 Management

◉ Iron therapy ◉ Oral iron ◉ IV iron ◉ Erythropoiesis-Stimulating Agents (ESAs) ◉ Transfusion ◉ Hypoxia-Inducible Factor-Prolylhydroxylase Inhibitors (HIF-PH inhibitors) / HIF Stabilizers ◉ Other medications

Iron therapy

◉ Oral iron ◉ Sodium ferrous citrate (Foliromin tab) ◉ Ferric hydroxide polymaltose (Ferrum hausmann chewable tab/drops) ◉ Polysaccharide iron complex+(Vit. B12)+Folic acid(Ferrin cap) ◉ IV iron ○ ferric hydroxide sucrose complex (Fe-back / Sucrofer)

Iron therapy

◉ IV iron ○ adverse effects : ■ hypersensitivity reactions including anaphylactic reactions ■ hypotension ■ iron toxicity ■ cramps, nausea, headache, vomiting, diarrhea ◉ Avoid IV iron in patients with active systemic infections

Iron therapy

◉ Consider in anemic CKD patient if TSAT ≤ 30% and serum ferritin ≤ 500 mcg/L ◉ Choice of oral or IV depends on ○ severity of iron deficiency ○ previous response and side effects ○ availability of venous access ○ patient compliance and cost

○ if the patient is on hemodialysis; most patients will require IV iron

Iron therapy

◉ Sucrosomial iron

Gómez-Ramírez S, et al. Sucrosomial® Iron: A New Generation Iron for Improving Oral Supplementation. Pharmaceuticals (Basel). 2018;11(4):97.

Giordano G., et al. Effectiveness of different oral iron formulations in iron deficiency anemia due to gastrointestinal bleeding: Multicentric randomized study. European Hematology Association; Stockholm, Sweden: 2018 Iron therapy

◉ 99 patients with CKD (stage 3–5, not on dialysis) ○ age >18 years ○ eGFR ≤60 mL/min/1.73 m2 ○ Hb levels ≤12 g/dL ○ plasma ferritin levels ≤100 ng/mL ○ transferrin saturation (TSAT) ≤25% ◉ Oral liposomal iron (30 mg/day, Group OS) VS. a total dose of 1000 mg of IV iron gluconate (125 mg infused weekly) (Group IV) for 3 months Iron therapy

The incidence of adverse event was significantly lower in the oral group (P < 0.001) Hypoxia-Inducible Factor-Prolylhydroxylase Inhibitors (HIF-PH inhibitors) / HIF Stabilizers

◉ ↑ HIF transcription factors ↑ endogenous ◉ 4 oral HIF stabilizers under investigation ○ , , , ○ Roxadustat is approved in China for treatment of anemia associated with chronic kidney disease

Gupta N, Wish JB. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD [published correction appears in Am J Kidney Dis. 2017 Jun;69(6):869].

◉ 204 in the roxadustat group VS. 101 in the epoetin alfa group ◉ oral roxadustat(100-120mg) VS. parenteral epoetin alfa(continued prerandomization doses) three times per week for 26 weeks ○ Doses were adjusted to keep a level of 10.0 to 12.0 g per deciliter

Other Medications

Anti-hepcidin drugs Iron-containing dialysate Gene therapy Activin traps Other Medications

Ascorbic acid(Vit. C) Androgens may improve hemoglobin may increase hemoglobin in and decrease erythropoietin adults with chronic kidney dose in patients with anemia disease-related anemia on hemodialysis ◉ Setting & population: Adult hemodialysis patients. ◉ Selection criteria for studies: Randomized clinical trials ◉ Intervention: Ascorbic acid use in addition to standard anemia management. ◉ Outcomes: Weighted mean difference (WMD) for change in hemoglobin level, recombinant human erythropoietin (rHuEPO) dose, transferrin saturation and ferritin level and adverse events.

◉ Results: 6 studies (n = 326 patients). Combining the 3 randomized clinical trials involving patients with baseline hemoglobin levels <11 g/dL, change in hemoglobin level was greater for ascorbic acid use compared with standard care (WMD, 0.9 g/dL; 95% CI, 0.5-1.2 g/dL). Compared with standard care, ascorbic acid use also was associated with a statistically significant decrease in rHuEPO dose (WMD, -17.1 U/kg/wk; 95% CI, -26.0 to -8.2 U/kg/wk) and improvement in transferrin saturation (WMD, 7.9%; 95% CI, 5.2-10.5%), with no change in ferritin concentration. ◉ Adverse events had questionable relevance to ascorbic acid use; no study reported oxalate levels or occurrence of oxalosis.

Change in hemoglobin concentration (grams per deciliter)

Change in recombinant human erythropoietin dose (units per kilogram per week)

Change in ferritin concentration (micrograms per liter)

Change in transferrin saturation (percentage)

Limitations

◉ Baseline characteristics of patients varied ○ Analyses that stratified by these factors resulted in effects consistent with those reported here. ◉ There is evidence that serum ascorbate levels are variable depending on the route of administration; ○ Sensitivity analyses eliminating the study using oral ascorbic acid did not change our results. ◉ Most studies included a modest number of subjects with short duration of treatment. ◉ Adverse-event reporting was limited across studies ○ possibly because of the low event rate in these trials. Limitations

◉ 2012 KDIGO: ○ The number of patients studied was insufficient to address the safety of this intervention. Thus the long-term safety of IV ascorbic acid in HD patients remains undefined, and whether secondary oxalosis should be a concern.

◉ Abstract only ◉ Setting: chronic hemodialysis patients and compared IV vitamin C with either a placebo or standard treatment ◉ 13 studies enrolling 497 patients ◉ Conclusion: Intravenous ascorbic acid in hemodialysis patients increases iron availability and decreases erythropoietin dose. The clinical significance of the observed increase in serum oxalale in this population is unclear. ◉ Abstract only ◉ Setting: prospective RCT, enrolled 18 anemic patients in HD with FID ◉ Oral 250 mg vitamin C daily for 3 months VS. control ◉ None of these participants had iron supplementation during the study period. ◉ Conclusion: ○ Daily low dose oral vitamin C supplementation helps to reduce Epo dose requirements in anemic hemodialysis patients with functional iron deficiency. ○ Despite concerns regarding oral vitamin C absorption in dialysis patients this study indicates Vitamin C is well tolerated and effective. ◉ Setting: prospective study included 22 stable patients in HD with FID ◉ Oral 250 mg vitamin C daily for three months ◉ None of these participants had iron supplementation during the study period ◉ Conclusion: Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID ◉ Abstract only ◉ Setting: open-label randomised parallel study, enrolled 191 chronic kidney disease patients not on haemodialysis ◉ 3 months of 500 mg oral ascorbic acid + IV TIW(n = 108) VS. IV iron sucrose alone TIW (n = 83) ◉ Conclusion: ○ Mean haemoglobin rise was higher when ascorbic acid is added compared to iv iron alone (10.1 vs. 11.3 mg/dL). ○ Mean serum ferritin rise with addition of ascorbic acid to iv iron was not statistically significant. Thanks for your listening !