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  • Title: Chronic renal allograft injury: early detection, accurate diagnosis and management.
    Author: Pascual J, Pérez-Sáez MJ, Mir M, Crespo M.
    Journal: Transplant Rev (Orlando); 2012 Oct; 26(4):280-90. PubMed ID: 22902496.
    Abstract:
    Chronic renal allograft injury (CRAI) is a multifactorial clinical/pathological entity characterised by a progressive decrease in glomerular filtration rate, generally associated with proteinuria and arterial hypertension. Classical views tried to distinguish between immunological (sensitization, low HLA compatibility, acute rejection episodes) and non-immunological factors (donor age, delayed graft function, calcineurin inhibitors [CNI] toxicity, arterial hypertension, infections) contributing to its development. Defining it as a generic idiopathic entity has precluded more comprehensive attempts for therapeutic options. Consequently, it is necessary to reinforce the diagnostic work-up to add etiopathogenetic diagnosis in any case of graft dysfunction, specially transplant vasculopathy and transplant glomerulopathy, reserving the term interstitial fibrosis and tubular atrophy (IFTA) when a case of CRAI is unspecific and no clear contributing factors or a specific etiology is possible in diagnosis. Earlier detection and intervention of CRAI remain as key challenges for transplant physicians. Changes in SCr levels and proteinuria often occur late in disease progression and may not accurately represent the underlying renal damage. Deterioration of renal function over time, determined through slope analysis, is a more accurate indicator of CRAI, and earlier identification of renal deterioration may prompt earlier changes in immunosuppressive therapies. The crucial point is probably to distinguish between nonimmunological or toxic CRAI and immunological-derived CRAI cases. Conversion to nonnephrotoxic immunosuppressants, such as mTOR inhibitors, holds promise in reducing the impact of toxic CRAI by both avoiding and reducing the impact of CNIs and reducing smooth muscle cell proliferation in the kidney. CRAI due to chronic antibody mediated rejection is an important entity, better and better defined that carries a bad prognosis and is associated with graft loss. The best prevention is adequate immunosuppression and tight patient monitoring, from the clinical, analytical and histological standpoint. While clinical trial evidence is needed for early detection and intervention in patients with CRAI, this review represents the current knowledge upon which clinicians can base their strategies. New prospective, ideally well-controlled trials are needed to establish the usefulness of different potentially therapeutic regimens. These evidences should demonstrate the benefits before extended uncontrolled use of drugs such as rituximab, bortezomib or eculizumab, which are expensive and frequently iatrogenic.
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