title: Reductions in red blood cell 2,3-diphosphoglycerate concentration during continuous renal replacment therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; ssharma6@partners.org.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000097:blood*; D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017674:Hypophosphatemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000378:metabolism; D010313:Partial Pressure; D017582:Renal Replacement Therapy / Q000009:adverse effects* / Q000379:methods*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010108:Oxyhemoglobins; D019794:2,3-Diphosphoglycerate; D010100:Oxygen
keywords: acute renal failure; dialysis; mortality