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Pathogenesis and Management of Chronic Allograft Nephropathy

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Abstract

Chronic allograft nephropathy (CAN) is a common cause of late kidney transplant failure, characterized by progressive histological damage in the allograft. Although functional biomarkers such as creatinine are typically used to predict CAN, recent evidence suggests that composite, quantitative histological indices may be better predictors of long-term graft outcomes. Calcineurin inhibitors (CNIs) have been associated with major improvements in early rejection outcomes, but appear to cause both acute and chronic nephrotoxicity. The acute phase is associated with functional nephrotoxicity and is reversible with a reduction in CNI dosage, whereas the chronic phase is characterized by persistent histological lesions that are typically irreversible. Results from recent clinical trials suggest that converting from a CNI to sirolimus, withdrawing a CNI from a sirolimus-based regimen or using a CNI-free strategy may improve long-term outcomes by reducing CNI-related nephrotoxicity. However, in the de novo transplant setting, triple therapy with sirolimus, mycophenolate mofetil and corticosteroids is not recommended in combination with basiliximab induction. A treatment algorithm, based on the patient’s histological score obtained on an allograft biopsy taken at approximately 6–12 months post-transplant, has been developed by our group and is described here.

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Acknowledgements

The authors would like to thank Dr Isabella Steffensen and Science & Medicine Canada for their editorial assistance in preparing this review. This work was supported by an unrestricted educational grant from Wyeth Canada. Dr Yilmaz has received honoraria and grants from Astellas, Novartis and Wyeth. Dr Sar reports no conflicts of interest.

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Authors and Affiliations

  1. Division of Transplant Surgery, University of Calgary, Calgary, Alberta, Canada

    Serdar Yilmaz (Medical Director)

  2. Southern Alberta Transplant Program (ALTRA), Foothills Medical Center, Rm 729 North Tower, 1403-29th Street NW, Calgary, Alberta, T2N 2T9, Canada

    Serdar Yilmaz (Medical Director) & Aylin Sar

  3. Foothills Medical Center, Calgary, Alberta, Canada

    Serdar Yilmaz (Medical Director)

  4. Division of Transplantation, Department of Pathology, University of Calgary, Calgary, Alberta, Canada

    Aylin Sar

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  1. Serdar Yilmaz
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Correspondence to Serdar Yilmaz.

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Yilmaz, S., Sar, A. Pathogenesis and Management of Chronic Allograft Nephropathy. Drugs 68 (Suppl 1), 21–31 (2008). https://doi.org/10.2165/00003495-200868001-00004

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