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Neutrophil gelatinase-associated lipocalin elimination by renal replacement therapy: minding the membrane!
Critical Care volume 20, Article number: 87 (2016)
The recently published data of Donadio in Critical Care provide convincing evidence that neutrophil gelatinase-associated lipocalin (NGAL), an established key biomarker of acute kidney injury (AKI) in the critically ill, can be effectively removed by renal replacement therapy (RRT) . His findings challenge recent work by Schilder et al.  and corroborate our concern regarding the potential removal of NGAL during continuous RRT (CRRT) . NGAL is expected to be eliminated by convection because its molecular weight (MW) lies below the 30-kDa MW cutoff point of “classic” dialysis membranes. Schilder et al. found almost no clearance of NGAL during continuous veno-venous hemofiltration despite using a 40-kDa MW (high) cutoff cellulose triacetate filter . Donadio used the same filter in patients undergoing high-flux maintenance hemodialysis (MHD) but applied an ultrafiltration rate more than twice as high as that of Schilder et al. (8474 versus 3700 ml/h per 100 mm Hg) and a higher sieving coefficient for middle molecules . Moreover, Donadio observed that hemodiafiltration (HDF) largely outperformed high-flux MHD in plasma NGAL removal (52.1 % versus 26.7 % reduction ratio) . This could be explained by a difference in membrane type. Cellulose triacetate filters have very poor adsorption capacity . In contrast, the acrylonitrile (AN) and natrium metallylsulfone copolymer membrane used for MHD in the Donadio study has characteristics similar to those of the highly adsorptive AN69 surface-treated membrane used for CRRT in critically ill patients . As this filter displays a lower MW cutoff than that of cellulose triacetate (30 versus 40 kDa), the remarkable removal of NGAL from plasma in patients undergoing HDF is not explained by increased convection alone but is likely related to additional membrane adsorption.
Taken together, the recent work  and comments including the additional data  of Donadio underscore that NGAL may lose significance to reflect severity and prognosis of AKI in patients receiving RRT because intensified convection or substantial adsorption (or both) on currently used dialysis membranes enhances plasma clearance of this biomarker.
Acute kidney injury
Continuous renal replacement therapy
Neutrophil gelatinase-associated lipocalin
Renal replacement therapy
Donadio C. Dialysis with high-flux membranes significantly affects plasma levels of neutrophil gelatinase-associated lipocalin. Crit Care. 2016;20:20.
Schilder L, Nurmohamed SA, ter Wee PM, Paauw NJ, Girbes AR, Beishuizen A, et al. The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied. Crit Care. 2014;18:R78.
Honore PM, Jacobs R, Hendrickx I, De Waele E, Van Gorp V, Spapen HD. Is neutrophil gelatinase-associated lipocalin unaffected by convective continuous renal replacement therapy? Definitely…maybe. Crit Care. 2015;19:392.
Donadio C. Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients. Crit Care. 2014;18:R39.
Honore PM, Jacobs R, Joannes-Boyau O, De Regt J, De Waele E, van Gorp V, et al. Newly designed CRRT membranes for sepsis and SIRS—a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review. ASAIO J. 2013;59:99–106.
The authors declare that they have no competing interests.
PMH and HDS designed the manuscript, participated in drafting it, and approved the final version.
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Honore, P.M., Spapen, H.D. Neutrophil gelatinase-associated lipocalin elimination by renal replacement therapy: minding the membrane!. Crit Care 20, 87 (2016). https://doi.org/10.1186/s13054-016-1258-9
- Renal Replacement Therapy
- Acute Kidney Injury
- Continuous Renal Replacement Therapy
- Molecular Weight Cutoff