Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

Abstract

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 (6SD) of 13.463.4 mmol/g Hgb to 11.063.1 mmol/g Hgb after 2 days of CRRT (P,0.001). Mean hemoglobin saturation P50 levels decreased from 29.764.4 mmHg to 26.764.0 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 mmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68 mmol/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 O 2 :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.

ASPEN Consensus Recommendations for Refeeding Syndrome

“…17,18 Depletion of phosphorus also decreases the production of 2,3-diphosphoglycerate, causing an increase in hemoglobin oxygen affinity, reduced oxygen release to tissues, and tissue hypoxia. 19 Serum concentrations of potassium decrease because of insulin stimulation of the Na + /K + ATPase, 16,20 a cell-wall enzyme that is responsible for flux of potassium into the cell and sodium out 18 and is essential in transmission of nerve impulses and contraction of muscles. 21,22 Hypokalemia may then result in impaired transmission of electrical impulses, increasing the risk of potentially lethal cardiac arrhythmias.…”

Precision Continuous Renal Replacement Therapy and Solute Control

“…Both hypophosphatemia and hypokalemia frequently complicate prolonged treatment. While initial phosphate removal may be indicated to achieve a biochemical target, continued removal can result in hypophosphatemia [6,7,19,20] . Hypophosphatemia has been associated with respiratory muscle weakness, delayed ventilator weaning, myocardial dysfunction and rhabdomyolysis, as well as with other complications.…”

Effect of Anemia on Cardiovascular Hemodynamics, Therapeutic Strategy and Clinical Outcomes in Patients With Heart Failure and Hemodynamic Congestion

“…These individuals may have a substantial capacity for maintaining oxygen delivery to peripheral tissue by increased tissue oxygen extraction that needs no further compensatory cardiovascular response including reduction in SVR and increase in cardiac output when anemia is not very severe. In contrast, among patients with HC, disability of compensative increases in 2,3-diphosphoglycerate (2,3-DPG) levels in red cells, a crucial allosteric effector of the affinity of Hb for oxygen, 20 and/or tissue damage may evoke further compensatory reduction in SVR and increased cardiac output. This arterial vasodilation causes hypotension and subsequent renal and visceral hypoperfusion, which can lead to elevated sympathetic activity, RAS activity and finally to volume retention.…”