Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors

Scientific Reports, vol. 14, pp. 12901

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.

Authors 9

1. Esther N. M. de Rooij corresponding Aachen Department of Clinical Epidemiology Department of Nephrology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. e.n.m.rooij@lumc.nl

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. e.n.m.rooij@lumc.nl

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

2. Ellen Karen Hoogeveen Aachen Department of Clinical Epidemiology Department of Nephrology, Leiden University Medical Center

   Leiden University Medical Center · Jeroen Bosch Ziekenhuis

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

   Department of Nephrology, Jeroen Bosch Hospital, Den Bosch, The Netherlands

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

3. Fred P.H.T.M. Romijn Aachen Department of Clinical Chemistry Laboratory Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands

4. Sandra van der Kooy Aachen Department of Nephrology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

5. Kristin V. Veighey

   University Hospital Southampton NHS Foundation Trust · Portsmouth Hospitals NHS Trust

   Affiliation as printed

   Research and Development, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK

   Wessex Kidney Centre, Portsmouth Hospitals NHS Trust, Portsmouth, Hampshire, UK

6. Friedo Wilhelm Dekker Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

7. Cees van Kooten Aachen Department of Nephrology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

8. Christa M. Cobbaert Aachen Department of Clinical Chemistry Laboratory Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands

9. Johan Willem de Fijter Aachen Department of Nephrology, Leiden University Medical Center

   University of Antwerp · Leiden University Medical Center · Antwerp University Hospital

   Affiliation as printed

   Department of Nephrology, Antwerp University Hospital, Edegem, Belgium

   Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

   Laboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Wilrijk, Belgium