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)

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Summary

Conclusions

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

Wolf G
22. Kaneku H
38. Liu YH
Findings
63. Eltzschig HK

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