Recent advances in renal interstitial fibrosis and tubular atrophy after kidney transplantation

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.

RETRACTED: Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair

“…Therefore, TGF‐β plays a major role in the generation of renal fibrosis by directly stimulating extracellular matrix components and reducing collagenase production, ultimately leading to renal scarring. Also, it was found that more than 70% of the renal biopsies from CsA treated transplant patients with chronic allograft fibrosis expressed high levels of TGF‐β . Hence, one can expect the involvement of the same nephrotoxic mechanism in the present study as a result of CsA administration.…”

Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach

“…Previous studies indicate that macrophages mediate endothelial cell cytotoxicity leading to loss of renal microvasculature74, are predictive of IF/TA development in an early biopsy75, and that M2-type macrophages promote the development of interstitial fibrosis in IF/TA7677. These studies support that macrophages play a significant role for IF/TA9. Our findings also support previous reports that the high CADI genes were enriched in proliferation of T and B cells, NK cell activation, and DC cell migration34, as well as two tolerance (TOL) biomarker lists (TOL vs. CAN) where NK and DC cell types are enriched in both liver and kidney transplantation7879.…”

“…Experimental studies in animal models attempting to treat IF/TA demonstrate effects in mitigating renal fibrosis. However, these experimental interventions prove to be difficult to implement in clinical practice, and currently available treatments cannot effectively prevent or revert the progression of IF/TA and improve renal graft function9101112. Chronic Allograft Dysfunction Index (CADI) is a broader histologic assessment for fibrosis in protocol biopsies that consists of 6 histologic parameters: interstitial inflammation in non-fibrotic areas (ii), interstitial fibrosis (IF), mesangial matrix (mm), vascular intimal proliferation (cv), tubular atrophy (TA), and glomerulosclerosis (gs)1314.…”

The farnesoid X receptor agonist EDP‐305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction

“…Peritubular capillary rarefaction and interstitial fibrosis are often observed in concordance with tubular epithelial injury. Mesenchymal activation, microvascular regression, and tubular atrophy often perpetuate a vicious cycle that culminates in the eventual deterioration of renal function (31). We evaluated the effects of targeting FXR with EDP-305 on peritubular capillary loss in the UUO model through dual immunofluorescence with the well-established fibrotic marker, a-SMA, and a vascular marker, CD31.…”