10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biological Pathways and Potential Targets for Prevention and Therapy of Chronic Allograft Nephropathy

      review-article

      * ,

      BioMed Research International

      Hindawi Publishing Corporation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Renal transplantation (RT) is the best option for patients with end-stage renal disease, but the half-life is limited to a decade due to progressive deterioration of renal function and transplant failure from chronic allograft nephropathy (CAN), which is the leading cause of transplant loss. Extensive research has been done to understand the pathogenesis, the biological pathways of fibrogenesis, and potential therapeutic targets for the prevention and treatment of CAN. Despite the advancements in the immunosuppressive agents and patient care, CAN continues to remain an unresolved problem in renal transplantation. The aim of this paper is to undertake a comprehensive review of the literature on the pathogenesis, biological pathways of RT fibrogenesis, and potential therapeutic targets for the prevention and therapy of CAN.

          Related collections

          Most cited references 123

          • Record: found
          • Abstract: found
          • Article: not found

          Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

          Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The natural history of chronic allograft nephropathy.

            With improved immunosuppression and early allograft survival, chronic allograft nephropathy has become the dominant cause of kidney-transplant failure. We evaluated the natural history of chronic allograft nephropathy in a prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had received kidney-pancreas transplants. We obtained 961 kidney-transplant-biopsy specimens taken regularly from the time of transplantation to 10 years thereafter. Two distinctive phases of injury were evident as chronic allograft nephropathy evolved. An initial phase of early tubulointerstitial damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and subclinical rejection (P<0.01) predicted mild disease by one year, which was present in 94.2 percent of patients. Early subclinical rejection was common (affecting 45.7 percent of biopsy specimens at three months), and the risk was increased by the occurrence of a prior episode of severe rejection and reduced by tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one year. Both subclinical rejection and chronic rejection were associated with increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of chronic allograft nephropathy was characterized by microvascular and glomerular injury. Chronic rejection (defined as persistent subclinical rejection for two years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional tubulointerstitial damage was accompanied by the use of calcineurin inhibitors. Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10 years, even in grafts with excellent early histologic findings. By 10 years, severe chronic allograft nephropathy was present in 58.4 percent of patients, with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular damage, once established, was irreversible, resulting in declining renal function and graft failure. Chronic allograft nephropathy represents cumulative and incremental damage to nephrons from time-dependent immunologic and nonimmunologic causes. Copyright 2003 Massachusetts Medical Society
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The hyperfiltration theory: a paradigm shift in nephrology.

              Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.
                Bookmark

                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                27 May 2014
                : 2014
                Affiliations
                Division of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK
                Author notes

                Academic Editor: Paul J. Higgins

                Article
                10.1155/2014/482438
                4058292
                Copyright © 2014 B. M. Shrestha and J. Haylor.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Comments

                Comment on this article