Managing Zinc Supplementation in Hemodialysis Patients: Balancing and Preventing Deficiencies in Serum Copper and Zinc Levels with and Without HIF-PH Inhibitors

Nutrients. 2024 Nov 29;16(23):4135. doi: 10.3390/nu16234135.

Abstract

Background/objectives: Zinc supplementation induces metallothionein, leading to reduced serum copper levels. Conversely, serum copper concentrations tend to rise with the use of HIF-PH inhibitors.

Methods: To establish a safe level of zinc supplementation that avoids copper deficiency, serum copper and zinc concentrations measured every three months were retrospectively analyzed over five years in 50 patients undergoing hemodialysis.

Results: At the initiation of the study, the median (IQR) concentrations were 100 (84.25-109) µg/dL for serum copper and 60.5 (50.5-70) µg/dL for serum zinc. All participants without zinc supplementation exhibited zinc deficiency (<80 µg/dL). After three months, copper deficiency (<71 µg/dL) was observed when serum copper concentrations were <98.6 µg/dL for patients with HIF-PH inhibitors and <90.3 µg/dL for patients without them. Reduced zinc supplementation may be necessary when serum copper falls below 90 µg/dL. Zinc levels remained deficient because supplementation was limited due to concerns about copper deficiency. Lowering the target zinc level to around 80 µg/dL instead of the conventional 80-120 µg/dL may be safer.

Conclusions: Regular monitoring of both copper and zinc levels, taking place at least every three months, is recommended to adjust zinc supplementation, especially in patients on HIF-PH inhibitors. Copper supplementation should also be considered alongside zinc supplementation to effectively treat hypozincemia.

Keywords: copper deficiencies; hemodialysis; hypoxia-inducible factor-prolyl hydroxylase inhibitors; zinc deficiency; zinc supplementation.

MeSH terms

  • Aged
  • Copper* / blood
  • Dietary Supplements*
  • Female
  • Glycine / analogs & derivatives
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors
  • Isoquinolines
  • Male
  • Middle Aged
  • Renal Dialysis*
  • Retrospective Studies
  • Zinc* / blood
  • Zinc* / deficiency

Substances

  • Zinc
  • Copper
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • roxadustat
  • Glycine
  • Isoquinolines

Grants and funding

This research received no external funding.