TY - JOUR
T1 - Kidney injury molecule-1 staining in renal allograft biopsies 10 days after transplantation is inversely correlated with functioning proximal tubular epithelial cells
AU - Bank, Jonna R.
AU - Van Der Pol, Pieter
AU - Vreeken, Dianne
AU - Monge-Chaubo, Catherine
AU - Bajema, Ingeborg M.
AU - Schlagwein, Nicole
AU - Van Gijlswijk, Daniëlle J.
AU - Van Der Kooij, Sandra W.
AU - Reinders, Marlies E.J.
AU - De Fijter, Johan W.
AU - Van Kooten, Cees
N1 - Publisher Copyright:
© The Author 2016.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Background. 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. Methods. 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. Results. 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 colocalization 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 q 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. Conclusions. KIM-1 and NGAL staining showed different localization and distribution. Quantitative KIM-1 staining was inversely correlated with functioning PTECs.
AB - Background. 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. Methods. 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. Results. 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 colocalization 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 q 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. Conclusions. KIM-1 and NGAL staining showed different localization and distribution. Quantitative KIM-1 staining was inversely correlated with functioning PTECs.
UR - http://www.scopus.com/inward/record.url?scp=85040096178&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfx286
DO - 10.1093/ndt/gfx286
M3 - Article
C2 - 29045706
AN - SCOPUS:85040096178
VL - 32
SP - 2132
EP - 2141
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 12
ER -