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Management of Chronic Allograft Nephropathy: A Systematic Review

Leora M. Birnbaum^*, Mark Lipman^*,, Steven Paraskevas^,, Prosanto Chaudhury^,, Jean Tchervenkov^,, Dana Baran^*,, Andrea Herrera-Gayol, and Marcelo Cantarovich^*,

^* Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada; Multi-Organ Transplant Program, McGill University Health Center; Department of Surgery, McGill University Health Center; ScienceMed Advice, Westmount, Quebec, Canada

Correspondence: Marcelo Cantarovich, MD, 687 Pine Avenue West, R2.58, Montreal, Quebec H3A 1A1, Canada. Phone: 514-934-1934 (#34969); Fax: 514-843-2815; E-mail: marcelo.cantarovich{at}muhc.mcgill.ca

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.