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Kidney injury molecule-1 staining in renal allograft biopsies 10 days after transplantation is inversely correlated with functioning proximal tubular epithelial cells.

Authors
  • Bank, Jonna R1
  • van der Pol, Pieter1
  • Vreeken, Dianne1
  • Monge-Chaubo, Catherine1
  • Bajema, Ingeborg M2
  • Schlagwein, Nicole1
  • van Gijlswijk, Daniëlle J1
  • van der Kooij, Sandra W1
  • Reinders, Marlies E J1
  • de Fijter, Johan W1
  • van Kooten, Cees1
  • 1 Department of Internal Medicine/Nephrology, Leiden University Medical Center, Leiden, The Netherlands. , (Netherlands)
  • 2 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Nephrology Dialysis Transplantation
Publisher
Oxford University Press
Publication Date
Dec 01, 2017
Volume
32
Issue
12
Pages
2132–2141
Identifiers
DOI: 10.1093/ndt/gfx286
PMID: 29045706
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are promising biomarkers for monitoring delayed graft function (DGF) after kidney transplantation. Here we investigated localization and distribution of KIM-1 and NGAL staining in renal allograft biopsies and studied their association with histological features, functional DGF (fDGF) and the tubular function slope (TFS), a functioning proximal tubular epithelial cell (PTEC) marker. Day 10 protocol biopsies of 64 donation after circulatory death recipients were stained for KIM-1 and NGAL and the positive area was quantified using ImageJ software. Biopsies were scored according to Banff and acute tubular necrosis (ATN) criteria. A 99mtechnetium-mercaptoacetyltriglycine (99mTc-MAG3)-renography was performed to calculate TFS. KIM-1 staining was located on the brush border of tubular epithelial cells (TECs) and correlated with denudation, while NGAL was present more focally in a cytoplasmic distribution. KIM-1 and NGAL staining were not correlated and no co-localization was observed. Quantitative stainings were not associated with fDGF, but KIM-1 tended to be higher in patients with prolonged fDGF (≥21 days; P = 0.062). No correlation was observed between the quantitative tissue stainings and urinary KIM-1 or NGAL. Quantitative KIM-1 staining was inversely correlated with the TFS (Spearman's ρ = -0.53; P < 0.001), whereas NGAL was not. The latter finding might be because cortical NGAL staining is dependent on filtration and subsequent reabsorption by functioning PTECs. Staining of NGAL was indeed restricted to PTECs, as shown by co-localization with a PTEC-specific lectin. KIM-1 and NGAL staining showed different localization and distribution. Quantitative KIM-1 staining was inversely correlated with functioning PTECs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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