Chronic allograft nephropathy.

Department of Laboratory Medicine and Pathology, University of Minnesota, USA.
Current Opinion in Nephrology and Hypertension (Impact Factor: 4.24). 04/2008; 17(2):149-55. DOI: 10.1097/MNH.0b013e3282f4e514
Source: PubMed

ABSTRACT Despite dramatic declines in acute rejection and early graft failure, long-term outcomes after kidney transplantation have improved little during the past 25 years. Most late allograft failure is attributed to chronic allograft nephropathy, but this is a clinicopathological description and not a diagnosis, and its pathogenesis and treatment are largely unknown.
Recent studies suggest that acute rejection during the first few months, and calcineurin inhibitor toxicity thereafter, may both contribute to chronic allograft nephropathy. There is also accumulating evidence that injury from antibody-mediated rejection may play an important pathogenic role in at least some patients with chronic allograft nephropathy, particularly those with transplant glomerulopathy. Therapeutic measures, including protocols to reduce calcineurin inhibitor exposure, remain largely unproven.
Understanding why so many kidney allografts fail, despite effective preventive measures for early acute rejection, is one of the most important areas of research in kidney transplantation today.


Available from: Behzad Najafian, Jun 03, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.
    Cell Biochemistry and Biophysics 11/2014; DOI:10.1007/s12013-014-0391-9 · 2.38 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic rejection is a poorly understood entity albeit a frequent cause of graft failure. Despite the advent of new immunosuppressive agents, neither the slope of graft destruction nor the frequency is ameliorated. There are a number of hypothesis which try to explain the conundrum of chronic graft destruction: ongoing rejection, antibody-mediated rejection, poor choice of organs, hyperfiltration, calcineurin inhibitors (CNI) nephrotoxicity and non-compliance among them. None of these hypotheses can explain all features of the process, thus, it is likely that they act in combination. What seems to be clear is a beneficial effect of early angiotensin-converting enzyme (ACE)/AT1 blocker treatment. It is less clear, however, whether a reduction or a switch from CNIs to other immunosuppressants prolongs graft survival. This review highlights the pathophysiological aspects that are important for the development of chronic allograft damage in the context of possible treatment options.
    Nephrology Dialysis Transplantation 04/2013; DOI:10.1093/ndt/gft087 · 3.49 Impact Factor