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

Shilpa Sharma, Shilpa Sharma, Carlo Brugnara, Rebecca Betensky, Sushrut S. Waikar

Research output: Contribution to journalArticle

Abstract

Background and objectivesHypophosphatemia 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 tissuesDesign, setting, participants, & measurementsPhosphate 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 modelsResultsMean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4µmol/g Hgb to 11.0±3.1µmol/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 0.53µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68µmol/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)ConclusionsCRRT-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.

Original languageEnglish (US)
Pages (from-to)74-79
Number of pages6
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2015

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2,3-Diphosphoglycerate
Renal Replacement Therapy
Erythrocytes
Kidney
Hemoglobins
Therapeutics
Phosphates
Oxygen
Confidence Intervals
Hypophosphatemia
Partial Pressure
Critical Illness
Gases

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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Reductions in red blood cell 2,3-diphosphoglycerate concentration during continuous renal replacment therapy. / Sharma, Shilpa; Sharma, Shilpa; Brugnara, Carlo; Betensky, Rebecca; Waikar, Sushrut S.

In: Clinical Journal of the American Society of Nephrology, Vol. 10, No. 1, 01.01.2015, p. 74-79.

Research output: Contribution to journalArticle

Sharma, Shilpa ; Sharma, Shilpa ; Brugnara, Carlo ; Betensky, Rebecca ; Waikar, Sushrut S. / Reductions in red blood cell 2,3-diphosphoglycerate concentration during continuous renal replacment therapy. In: Clinical Journal of the American Society of Nephrology. 2015 ; Vol. 10, No. 1. pp. 74-79.
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abstract = "Background and objectivesHypophosphatemia 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 tissuesDesign, setting, participants, & measurementsPhosphate 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 modelsResultsMean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4µmol/g Hgb to 11.0±3.1µmol/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 0.53µmol/g Hgb per 1 g phosphate removed (95{\%} confidence interval 0.38 to 0.68µmol/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)ConclusionsCRRT-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.",
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AU - Waikar, Sushrut S.

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N2 - Background and objectivesHypophosphatemia 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 tissuesDesign, setting, participants, & measurementsPhosphate 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 modelsResultsMean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4µmol/g Hgb to 11.0±3.1µmol/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 0.53µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68µmol/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)ConclusionsCRRT-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.

AB - Background and objectivesHypophosphatemia 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 tissuesDesign, setting, participants, & measurementsPhosphate 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 modelsResultsMean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4µmol/g Hgb to 11.0±3.1µmol/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 0.53µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68µmol/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)ConclusionsCRRT-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.

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