In the article “Biomarker-Based Management of AKI: Fact or Fantasy?” [Nephron. 2021, DOI: 10.1159/000518365] by Ostermann et al., the authors missed to indicate in Table 2 (8th row, last column) that the finding of elevated cell cycle arrest markers in patients with diabetes was inconsistent between studies. The corrected Table 2 is shown below.
Table 2.
Description and characteristics of selected AKI biomarkers (adapted from reference [10])
| AKI biomarker | Biological role | Biological sample | Stress marker | Damage marker | Functional marker | Roles in practice | Populations studied | Limitations |
|---|---|---|---|---|---|---|---|---|
| Alanine aminopeptidase (AAP); Alkaline phosphatase (ALP); γ-glutamyl transpeptidase (γ-GT) | enzymes located on the brush border of proximal tubular cells; released into urine after tubular damage | urine | X | diagnosis and severity of AKI | ICU | elevated in UTI, cardiovascular disease, stroke | ||
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| C-C motif chemokine ligand 14 (CCL 14) | pro-inflammatory chemokine; released into urine following tubular cell stress/damage | urine | X | kidney recovery | ICU | performance might vary in different AKI phenotypes | ||
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| Chitinase 3-like protein 1 | 39 kDa intracellular protein of glycoside hydrolase family; expressed by endothelial cells, macrophages & neutrophils and released into the urine and plasma | urine plasma | X | diagnosis of AKI | cardiac surgery ICU | limited performance in real-world settings as a single biomarker | ||
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| Cystatin C | 13 kDa cysteine protease inhibitor produced by nucleated human cells; freely filtered | plasma | X | diagnosis of AKI and measurement of severity | cardiac surgery liver transplantation hospitalized patients | confounded by age, sex, inflammatory state, diabetes, low albumin, muscle mass, high dose steroids | ||
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| Dickkopf-3 (DKK3) | 38kDa renal tubular cell-derived glycoprotein; secreted into urine under tubular stress conditions | urine | X | risk assessment and prediction of AKI | cardiac surgery | elevated in CKD | ||
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| Hepatocyte growth factor (HGF) | antifibrotic cytokine produced by mesenchymal cells; involved in tubular cell regeneration after AKI and measured in plasma | plasma | X | severity of AKI and renal recovery | hospitalized | limited performance | ||
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| Hepcidin | 2.78 kDa peptide hormone predominantly produced in hepatocytes; freely filtered into urine and plasma | urine plasma | X | diagnosis of AKI and assessment of severity | cardiac surgery ICU | decreased in anemia and increased in inflammatory state | ||
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| Tissue metalloproteinase-2 (TIMP-2); Insulin-like growth factor binding protein 7 (IGFB7) | metalloproteinases released during tubular cell cycle arrest (cell cycle arrest biomarker) | urine | X | prediction and diagnosis of AKI and assessment of severity | cardiac and non-cardiac surgery ICU | elevated in diabetes (inconsistent finding in studies) | ||
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| Interleukin-18 (IL-18) | 18 kDa pro-inflammatory cytokine; released into urine following tubular cell damage | urine | X | prediction and diagnosis of AKI | hospitalized patients ICU ED cardiac surgery | elevated in inflammatory state lack of cut-off values | ||
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| Kidney Injury Molecule-1 (KIM-1) | transmembrane glycoprotein produced by proximal tubular cell; released into urine after tubular cell damage | urine | X | prediction and diagnosis of AKI and assessment of severity | hospitalized patients ED cardiac surgery ICU | elevated in chronic proteinuria and inflammatory diseases. | ||
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| Liver-type fatty acid-binding protein (L-FABP) | 14 kDa intracellular lipid chaperone; freely filtered and reabsorbed in proximal tubule; excreted into urine after tubular cell damage and measured in the urine and plasma | urine plasma | X | diagnosis of AKI | cardiac surgery ICU ED | associated with anemia in nondiabetic patients | ||
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| N-acetyl-ß-D-glucosaminidase (NAG) | >130 kDa lysosomal enzyme; released into urine after tubular damage | urine | X | diagnosis of AKI | cardiac surgery hospitalized patients | elevated in diabetes and albuminuria | ||
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| Neutrophil gelatinase-associated lipocalin (NGAL) | at least 3 different types measured in the urine and plasma: i) | monomeric 25kDa glycoprotein produced by neutrophils and epithelial tissues, including tubular cells ii) | homodimeric 45kDa protein produced by neutrophils iii) heterodimeric 135kDa protein produced by tubular cells | urine plasma | X | diagnosis of AKI and measurement of severity | cardiac and non-cardiac surgery coronary angiography ICU hospitalized patients post-transplant ED | elevated in sepsis, UTI, CKD lack of specific cut-off values |
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| Netrin-1 | 50-75kDa laminin-related molecule minimally expressed in proximal tubular cells of normal kidneys; released into urine after tubular cell damage | urine | X | diagnosis of AKI | cardiac surgery | limited data in high- risk settings e.g. CKD, diabetes, critial illness | ||
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| Proenkephalin A (PENK) | endogenous polypeptide hormone in adrenal medulla, immune system and renal tissue; freely filtered and measured in plasma | plasma | X | diagnosis and assessment of severity of AKI and renal recovery | ICU cardiac surgery hospitalized patients | |||
AKI, acute kidney injury; CKD, chronic kidney disease; ED, emergency department; ICU, intensive care unit; UTI, urinary tract infection.