Abstract
Although kidney transplantation has been an important means for the treatment of patients with end stage of renal disease, the long-term survival rate of the renal allograft remains a challenge. The cause of late renal allograft loss, once known as chronic allograft nephropathy, has been renamed “interstitial fibrosis and tubular atrophy” (IF/TA) to reflect the histologic pattern seen on biopsy. The mechanisms leading to IF/TA in the transplanted kidney include inflammation, activation of renal fibroblasts, and deposition of extracellular matrix proteins. Identifying the mediators and factors that trigger IF/TA may be useful in early diagnosis and development of novel therapeutic strategies for improving long-term renal allograft survival and patient outcomes. In this review, we highlight the recent advances in our understanding of IF/TA from three aspects: pathogenesis, diagnosis, and treatment.
Highlights
Kidney transplantation has been an important means for the treatment of patients with end stage of renal disease, the long-term survival rate of the renal allograft remains a challenge
interstitial fibrosis and tubular atrophy” (IF/TA) is associated with decreased graft survival, especially when it is accompanied by transplant vasculopathy, subclinical rejection, or transplant glomerulopathy
In the past several decades, numerous studies have been conducted to understand the pathogenesis of IF/TA and multiple factors and mechanisms have been demonstrated to be involved in the progress of the IF/TA, including immunosuppressive drug toxicity, antibody-mediated injury, and epithelial– mesenchymal transition (EMT) (Figure 1)
Summary
Long-term renal allograft survival after kidney transplantation remains variable, depending on a host of factors. Recent studies have suggested that immunosuppressive drug toxicity, antibody-mediated injury, EMT, pro-inflammatory, and pro-fibrosis factors are involved in the IF/TA. Multiple approaches, such as monitoring blood and urine samples, may be promising tools for early detection of IF/TA. Abbreviations ADAM17: A disintegrin and metalloproteinase 17; ALA: Alpha-lipoic acid; AMR: Antibody-mediated rejection; BMP-7: Bone morphogenetic protein 7; CAN: Chronic allograft nephropathy; CNI: Calcineurin inhibitor; CsA: Cyclosporine; CTGF: Connective tissue growth factor; dDSA: de novo DSA; DSA: Donor specific antibody; EGFR: EGF receptor; eGFR: Estimated glomerular filtration rate; EMT: Epithelial–mesenchymal transition; HB-EGF: Heparin binding epidermal growth factor; HIF-1α: Hypoxia-inducible factor-1α; IF/TA: Interstitial fibrosis and tubular atrophy; KIM-1: Kidney injury molecule-1; miRNAs: microRNAs; MMPs: Matrix metalloproteinases; MSC: Mesenchymal stem cell; NCTD: Norcantharidin; rHuEPO: Human erythropoietin; TGF-β: Transforming growth factor-β; TIMPs: Tissue inhibitors of metalloproteinases; uVDBP: Urinary vitamin D binding protein. Authors’ contributions XL wrote and revised the manuscript; SZ wrote and edited the manuscript Both authors read and approved the final manuscript
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