title: The over-exaggerated chronic nephrotoxicity of calcineurin inhibitors.
abstract: BACKGROUND
  Late kidney allograft failure remains a major problem in kidney transplantation. While there is no doubt that acute nephrotoxicity from calcineurin inhibitors (CNIs) exists, chronic CNI nephrotoxicity has been the subject of much debate in the transplant community.
  
  
  METHODS
  We identified original articles related to the use of CNIs in renal and extra-renal solid-organ transplantation, to examine the available evidence about their chronic nephrotoxicity.
  
  
  RESULTS
  There is clearly a lack of firm evidence for the role of CNIs as a major injurious agent causing chronic renal dysfunction and allograft failure. Moreover, recent evidence shows that the pathological lesions typically linked to chronic CNI use are not specific. A growing body of evidence shows that alloimmunity is a much more important cause of late renal allograft failure.
  
  
  CONCLUSIONS
  More research should focus on addressing the true causes of chronic graft dysfunction rather than continuing to propagate the exaggerated contribution of CNIs to late graft loss.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Naim
authors.initials: N
authors.lastname: Issa
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kukla
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Hassan N
authors.initials: HN
authors.lastname: Ibrahim
keywords: AR, acute rejection; AZA, azathioprine; CKD, chronic kidney disease; CNI, calcineurin inhibitor; CSA, cyclosporin A; Calcineurin inhibitors; Chronic kidney disease; Chronic nephrotoxicity; Graft loss; Kidney transplantation; MMF, mycophenolate mofetil