Chronic Renal Allograft Dysfunction: Risk Factors, Immunology and Prevention

Introduction: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Despite great progress in surgical aspects and immunosupression therapy, long-term graft survival has not been consistent. Chronic allograft dysfunction (CAD) remains a major cause of late grafts failure. Review: CAD is a generic term of all causes of chronic renal allograft dysfunction associated with fibrosis. It is clinically characterized by a gradual worsening of renal function in the presence of arterial hypertension and low-grade proteinuria. Histological changes of CAD usually precede functional deterioration and include interstitial fibrosis/tubular atrophy accompanied by vascular changes and glomerulosclerosis. Both immunological and non immunological factors can be responsible for CAD. Immunological causes include chronic active antibody-mediated and T cell-mediated rejection. Non immunological factors include brain death in the donor, increasing donor age, ischemia-reperfusion injury, calcineurin inhibitor nephrotoxicity, hypertension, diabetes mellitus, hyperlipidemia, chronic obstruction and chronic viral infections. Even if the contributing factors to CAD can be identified, not all of them can be interrupted prior to and after grafting. Preventive strategies include improvements in medical and surgical strategies to reduce ischemia-reperfusion injury, strategies to minimize acute rejection and strategies aiming for HLA-matched transplants. Additional measures include tight control of blood pressure, proteinuria, lipids and glucose. Antivirus treatment, appropriate diet, weight control, no smoking and good compliance are also suggested in certain settings. Conclusion: Evidence-based treatment strategies for CAD are lacking, but several prevention and management strategies are recommended in clinical practice.