Management of Chronic Allograft Nephropathy

Abstract

Despite improving immunosuppressive protocols in renal transplantation, chronic allograft nephropathy (CAN) remains a major impediment to long-term graft survival. The optimal immunosuppressive regimen for a patient with CAN is unknown. The aim of this study is to evaluate the various immunosuppressive management strategies of biopsy-proven CAN and of chronic allograft dysfunction (CAD) (no biopsy). A systematic review of randomized trials (n ‫؍‬ 12 trials with 635 patients) was conducted. Studies included patients who were >6 mo post-transplant. All patients were on a calcineurin inhibitor (CNI), most often cyclosporine, and were randomized to convert to mycophenolate mofetil (MMF), tacrolimus, or sirolimus (Rapa) or to add azathioprine, MMF or Rapa to their current regimen. Follow-up time was 6 to 36 mo. The outcome measures evaluated were renal function in 11 of 12 studies and repeat renal biopsy results in one study. The methodological quality scores of the trials were generally low, using the Jadad scale (median value 2/5). Results varied between studies but suggested that CNI withdrawal is safe and that conversion to MMF or Rapa may be beneficial. The incidence of adverse effects ranged from 0% to 68% between the studies, and medication withdrawal occurred in 0% to 24% of patients. The review did not result in a consensus regarding the management of CAN and CAD. Further studies are required to determine the best therapeutic option for patients with CAD and CAN.

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

“…The kidneys were classified as either TX or CAN/IFTA based on morphological examination of the biopsies and Banff criteria (17). Chronic allograft nephropathy is an evolved terminology that describes the chronic progressive decline in allograft kidney function that is variably associated with transplant glomerulopathy, peritubular capillaropathy, transplant arteriopathy, tubular atropathy, and interstitial fibrosis (20,21).…”

Advantages and Controversies in the Era of Intrarenal Volumetry

“…In current clinical practice, volume measurements are not usually used in routine examinations of renally impaired patients. Nonetheless, we refer to several renopathological conditions where volumetry would be clinically important because renal size gives insight into renal functional reserve or the extent of renal injury, including glomerulonephritis [8,9], allograft nephropathy [10], parenchymal renal diseases [11], renal artery stenosis [12,13,14], and UO [19]. High-resolution MRI is capable of delineating particular intrarenal structures without radiation exposure and provides excellent tissue contrast.…”

“…Conversely, light, electron and immunofluorescence microscopy (of biopsy samples) have been invaluable in renal pathology for the study of glomerular structure, ultrastructural details of the glomerular capillary wall and the glomerular basement membrane, tubuli and the interstitium [5,6,7]. However, traditional biopsies only contain 10–20 glomeruli out of approximately 1 million, and quantitative assessments are limited, although they are important in the assessment of most kidney diseases, particularly in glomerulonephritis [8,9], allograft nephropathy [10], and the evaluation of chronic injury in parenchymal renal diseases [11]. When the kidneys shrink due to fibrosis and tissue destruction, a biopsy is associated with a high risk of bleeding and frequently provides limited information.…”

Concomitant Face/Upper Extremity Allotransplantation

“…Chronic rejection, which is well described in solid organ transplantation and continues to have a very significant impact on long-term survival of organ allografts, has not yet been reported in face transplantation [27,28]. One hand allograft loss, in which intimal hyperplasia was observed on histological examination, may have been attributable to chronic rejection, however other factors may have been involved and the etiology in this case is not clear [29].…”