Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients

Nephrol Dial Transplant. 2000 Aug;15(8):1207-11. doi: 10.1093/ndt/15.8.1207.

Abstract

Background: Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the hypothesis that dialysate-related cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis fluids, differing in their microbiological quality, on the rHuEpo therapy.

Methods: Thirty male patients with end-stage renal disease maintained on regular haemodialysis were assigned either to a group treated with conventional (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online-produced ultrapure dialysate (group II). Randomization was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10-10.5 g/dl. Patients were followed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly and serum ferritin concentrations were determined at 6-week intervals. C-reactive protein (CRP) and interleukin-6 (IL-6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months.

Results: In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was associated with elevated surrogate markers (CRP, IL-6) of cytokine-induced inflammation. The switch from conventional to online-produced ultrapure dialysate in group II resulted in a lower bacterial contamination with a significant decrease of CRP and IL-6 blood levels. It was accompanied by a significant and sustained reduction of the rHuEpo dosage, which was required to correct the anaemia. Using multiple regression analysis, IL-6 levels are shown to have a strong predictive value for rHuEpo dosage in both groups.

Conclusions: Our data demonstrate that dialysate-related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL-6. Dialysate-related cytokine induction might diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in a better response to rHuEpo. Not only would it save money, but it would also help to maintain an optimal haemoglobin level without further increase in rHuEpo dosage.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Bacteria / isolation & purification
  • Bicarbonates / therapeutic use
  • Cytokines / blood*
  • Dialysis Solutions / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Contamination
  • Erythropoietin / administration & dosage
  • Erythropoietin / therapeutic use*
  • Hemoglobins / analysis
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Recombinant Proteins / therapeutic use
  • Renal Dialysis*

Substances

  • Bicarbonates
  • Cytokines
  • Dialysis Solutions
  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin