Reductions in red blood cell 2,3-diphosphoglycerate concentration during continuous renal replacment therapy

Clin J Am Soc Nephrol. 2015 Jan 7;10(1):74-9. doi: 10.2215/CJN.02160214. Epub 2014 Dec 23.


Background and objectives: Hypophosphatemia is a frequent complication during continuous renal replacement therapy (CRRT), a dialytic technique used to treat AKI in critically ill patients. This study sought to confirm that phosphate depletion during CRRT may decrease red blood cell (RBC) concentration of 2,3-diphosphoglycerate (2,3-DPG), a crucial allosteric effector of hemoglobin's (Hgb's) affinity for oxygen, thereby leading to impaired oxygen delivery to peripheral tissues.

Design, setting, participants, & measurements: Phosphate mass balance studies were performed in 20 patients with severe AKI through collection of CRRT effluent. RBC concentrations of 2,3-DPG, venous blood gas pH, and oxygen partial pressure required for 50% hemoglobin saturation (P50) were measured at CRRT initiation and days 2, 4, and 7. Similar measurements were obtained on days 0 and 2 in a reference group of 10 postsurgical patients, most of whom did not have AKI. Associations of 2,3-DPG with laboratory parameters and clinical outcomes were examined using mixed-effects and Cox regression models.

Results: Mean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4 µmol/g Hgb to 11.0±3.1 µmol/g Hgb after 2 days of CRRT (P<0.001). Mean hemoglobin saturation P50 levels decreased from 29.7±4.4 mmHg to 26.7±4.0 mmHg (P<0.001). No significant change was seen in the reference group. 2,3-DPG levels after 2 days of CRRT were not significantly lower than those in the reference group on day 2. Among patients receiving CRRT, 2,3-DPG decreased by 0.53 µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68 µmol/g Hgb; P<0.001). Greater reductions in 2,3-DPG were associated with higher risk for death (hazard ratio, 1.43; 95% confidence interval, 1.09 to 1.88; P=0.01).

Conclusions: CRRT-induced phosphate depletion is associated with measurable reductions in RBC 2,3-DPG concentration and a shift in the O2:Hgb affinity curve even in the absence of overt hypophosphatemia. 2,3-DPG reductions may be associated with higher risk for in-hospital death and represent a potentially avoidable complication of CRRT.

Keywords: acute renal failure; dialysis; mortality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3-Diphosphoglycerate / blood*
  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / therapy*
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Case-Control Studies
  • Down-Regulation
  • Erythrocytes / metabolism*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hypophosphatemia / blood
  • Hypophosphatemia / diagnosis
  • Hypophosphatemia / etiology*
  • Male
  • Middle Aged
  • Oxygen / blood
  • Oxyhemoglobins / metabolism
  • Partial Pressure
  • Renal Replacement Therapy / adverse effects*
  • Renal Replacement Therapy / methods*
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Oxyhemoglobins
  • 2,3-Diphosphoglycerate
  • Oxygen