Chronic Humoral Rejection of Human Kidney Allografts Is Associated with MMP‐2 Accumulation in Podocytes and its Release in the Urine

Chronic humoral rejection (CHR) is an important cause of late graft failures following kidney transplantation. Overall, the pathophysiology of CHR is poorly understood. Matrix metalloproteinase‐2 (MMP‐2), a type IV collagenase, has been implicated in chronic kidney disease and allograft rejection in previous studies. We examined the presence of MMP‐2 in allograft biopsies and in the urine of kidney transplant recipients with CHR. MMP‐2 staining was detected by immunohistochemistry in podocytes for all CHR patients but less frequently in patients with other renal complications. Urinary MMP‐2 levels were also significantly higher in CHR patients (median 4942 pg/mL, N = 27) compared to non‐CHR patients (median 598 pg/mL, N = 65; p < 0.001). Elevated urinary MMP‐2 correlated with higher levels of proteinuria in both CHR and non‐CHR patients. Longitudinal analysis indicated that increase in urine MMP‐2 coincided with initial diagnosis of CHR as documented by the biopsies. Using an enzymatic assay, we demonstrated that MMP‐2 was present in its active form in the urine of patients with CHR. Overall, our findings associate MMP‐2 with glomerular injury as well as interstitial fibrosis and tubular atrophy observed in patients with CHR.

• Publication year

  2010

• Venue

  American Journal of Transplantation

• Publication date

  2010-11-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1111/j.1600-6143.2010.03290.xPMID 20977637PMCID PMC3805271
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Banff ’09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups

  2010cited by this paper
• Chronic Humoral Rejection of Human Kidney Allografts Associates With Broad Autoantibody Responses

  2010cited by this paper
• The Cellular Lesion of Humoral Rejection: Predominant Recruitment of Monocytes to Peritubular and Glomerular Capillaries

  2007cited by this paper
• Four‐year Follow‐up of a Prospective Trial of HLA and MICA Antibodies on Kidney Graft Survival

  2007cited by this paper
• Antibody-mediated renal allograft rejection: diagnosis and pathogenesis.

  2007cited by this paper
• Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis.

  2007influential reference
• Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury

  2006cited by this paper
• Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients with various glomerular diseases and their implication in pathogenetic lesions: study based on an enzyme-linked assay and immunohistochemical staining

  2006cited by this paper
• High Ambient Glucose Levels Modulates the Production of MMP-9 and a5(IV) Collagen by Cultured Podocytes

  2006cited by this paper
• Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation.

  2005cited by this paper
• Predictive Value of HLA Antibodies and Serum Creatinine in Chronic Rejection: Results of a 2-year Prospective Trial

  2005cited by this paper
• Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis.

  2004cited by this paper
• Lack of Improvement in Renal Allograft Survival Despite a Marked Decrease in Acute Rejection Rates Over the Most Recent Era

  2004cited by this paper
• Antibody‐Mediated Rejection Criteria – an Addition to the Banff ′97 Classification of Renal Allograft Rejection

  2003cited by this paper
• Endothelial signaling in kidney morphogenesis: a role for hemodynamic forces.

  2002cited by this paper
• Macrophage‐derived MT1‐MMP and increased MMP‐2 activity are associated with glomerular damage in crescentic glomerulonephritis

  2000cited by this paper
• Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

  2000cited by this paper
• The Banff 97 working classification of renal allograft pathology.

  1999cited by this paper
• ECM degradation by cultured human mesangial cells is mediated by a PA/plasmin/MMP-2 cascade.

  1995cited by this paper
• Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis.

  1992cited by this paper

• Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles

  2025cites this paper
• Matrix Metalloproteinases in Ureteropelvic Junction Obstruction: Their Role in Pathogenesis and Their Use as Clinical Markers

  2025cites this paper
• Matrix metalloproteinases in kidney homeostasis and diseases: an update.

  2024cites this paper
• COL4A3 Mutation Induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2

  2023cites this paper
• Coupling hCG-based protease sensors with a commercial pregnancy test strip for simple analyses of protease activities.

  2023cites this paper
• Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal

  2019cites this paper
• Serological cytokine profiles of cardiac rejection and lung infection after heart transplantation in rats

  2019cites this paper
• Non-invasive quantification of collagen turnover in renal transplant recipients

  2017cites this paper
• Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target.

  2017cites this paper
• Matrix Metalloproteinase-2 (MMP-2) and Plasminogen Activator Inhibitor-1 (PAI-1) in Peritoneal Dialysis: Biological Implications and Clinical Utility

  2015cites this paper
• An analysis of the impact of pre‐analytical factors on the urine proteome: Sample processing time, temperature, and proteolysis

  2015cites this paper
• Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

  2014cites this paper
• Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo

  2014cites this paper
• Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients.

  2014cites this paper
• The importance of MMPs/TIMPs system for impaired degradation of extracellular matrix in chronic kidney allograft injury

  2014cites this paper
• Effects of pulsed and sinusoidal electromagnetic fields on MMP-2, MMP-9, collagen type IV and E-cadherin expression levels in the rat kidney: an immunohistochemical study.

  2013cites this paper
• Increased plasma tissue inhibitors of metalloproteinase concentrations as negative predictors associated with deterioration of kidney allograft function upon long-term observation.

  2013cites this paper
• Le fragment LG3 du perlécan : un nouveau régulateur de remodelage vasculaire en transplantation

  2013cites this paper
• The Allo-Immunological Injury in Chronic Allograft Nephropathy

  2012cites this paper
• Matrix metalloproteinases in kidney homeostasis and diseases.

  2012cites this paper
• Common variation in GPC5 is associated with acquired nephrotic syndrome

  2011cites this paper
• Imbalance of metallaproteinase/tissue inhibitors of metalloproteinase system in renal transplant recipients with chronic allograft injury.

  2011cites this paper
• All-trans retinoic acid can regulate the expressions of gelatinases and apolipoprotein E in glomerulosclerosis rats.

  2011cites this paper