Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors
Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors
Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.
Humans, Nephrectomy/methods, Tissue Inhibitor of Metalloproteinase-2/urine, beta 2-Microglobulin/urine, Male, Female, Middle Aged, Insulin-Like Growth Factor Binding Proteins/urine, Adult, Biomarkers/urine, Kidney Transplantation/adverse effects, Living Donors, Kidney/surgery, Hepatitis A Virus Cellular Receptor 1/metabolism, Creatinine/urine, Lipocalin-2/urine
de Rooij, Esther N.M.
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Hoogeveen, Ellen K.
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Romijn, Fred P.H.T.M.
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van der Kooy, Sandra W.
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Veighey, Kristin V.
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Dekker, Friedo W.
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van Kooten, Cees
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Cobbaert, Christa M.
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de Fijter, Johan W.
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5 June 2024
de Rooij, Esther N.M.
bd7716ac-25b9-46d9-a009-7e76f632ed70
Hoogeveen, Ellen K.
852770b4-8ab1-461a-8e2c-6308f79274d7
Romijn, Fred P.H.T.M.
c9c84159-669a-4b36-bc97-4b9a387d8e7e
van der Kooy, Sandra W.
107f4749-af8c-4984-94ca-7cf8d9004ff8
Veighey, Kristin V.
2adbaf5c-141a-44bd-a7eb-faf14e0ca251
Dekker, Friedo W.
28c0e7f3-55c0-4d02-a4cd-952895ad81a9
van Kooten, Cees
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Cobbaert, Christa M.
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de Fijter, Johan W.
a7081d17-bac3-4f95-ad0e-70840d5682f9
de Rooij, Esther N.M., Hoogeveen, Ellen K., Romijn, Fred P.H.T.M., van der Kooy, Sandra W., Veighey, Kristin V., Dekker, Friedo W., van Kooten, Cees, Cobbaert, Christa M. and de Fijter, Johan W.
(2024)
Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors.
Scientific Reports, 14 (1), [12901].
(doi:10.1038/s41598-024-62246-1).
Abstract
Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.
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s41598-024-62246-1
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More information
Accepted/In Press date: 15 May 2024
Published date: 5 June 2024
Keywords:
Humans, Nephrectomy/methods, Tissue Inhibitor of Metalloproteinase-2/urine, beta 2-Microglobulin/urine, Male, Female, Middle Aged, Insulin-Like Growth Factor Binding Proteins/urine, Adult, Biomarkers/urine, Kidney Transplantation/adverse effects, Living Donors, Kidney/surgery, Hepatitis A Virus Cellular Receptor 1/metabolism, Creatinine/urine, Lipocalin-2/urine
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Local EPrints ID: 508341
URI: http://eprints.soton.ac.uk/id/eprint/508341
ISSN: 2045-2322
PURE UUID: 3e7560dc-0a35-495f-8a78-2465308297c9
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Date deposited: 19 Jan 2026 17:39
Last modified: 20 Jan 2026 02:56
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Contributors
Author:
Esther N.M. de Rooij
Author:
Ellen K. Hoogeveen
Author:
Fred P.H.T.M. Romijn
Author:
Sandra W. van der Kooy
Author:
Friedo W. Dekker
Author:
Cees van Kooten
Author:
Christa M. Cobbaert
Author:
Johan W. de Fijter
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