Challenges and considerations in diagnosing the kidney disease in deteriorating graft function

Abstract

Despite significant reductions in acute-rejection rates with the introduction of calcineurin inhibitor (CNI)-based immunosuppressive therapy, improvements in long-term graft survival in renal transplantation have been mixed. Improving long-term graft survival continues to present a major challenge in the management of kidney-transplant patients. CNIs are a key component of immunosuppressive therapy, and chronic CNI toxicity has been widely thought to be a major factor in late graft failure. However, recent studies examining the causes of late graft failure in detail have challenged this view, highlighting the importance of antibody-mediated rejection and other factors. In addition, the diagnosis of CNI nephrotoxicity represents a challenge to clinicians, with the potential for over-diagnosis and an inappropriate reduction in immunosuppressive therapy. When graft function is deteriorating, accurately determining the cause of the kidney disease is essential for effective long-term management of the patient. Diagnosis requires a thorough clinical investigation, and in the majority of cases a specific cause can be identified.

Figure 1

Kaplan–Meier estimates of the impact of (a) diagnosis of CNI toxicity and (b) presence or absence of C4d and DSA on graft survival in the DeKAF study [5]. Reprinted from: Gaston et al. [5].

Figure 2

Overview of investigations to determine the cause of kidney disease in patients with deteriorating graft function. AUC, area under the curve; DSA, donor-specific antibodies; MPA, mycophenolic acid.