Published online Oct 28, 2019. doi: 10.5500/wjt.v9.i6.123
Peer-review started: June 9, 2019
First decision: August 2, 2019
Revised: September 17, 2019
Accepted: October 2, 2019
Article in press: October 2, 2019
Published online: October 28, 2019
Although, there have been significant improvements in early graft survival due to advances in immunosuppression and the overall medical care of transplant recipients. However, long-term graft survival has only had modest improvement. The causes of “true” late kidney allograft failure remain unclear.
In this study, we explored the causes of graft failure based on various histopathological findings after transplant in the current era, which may allow providers to determine interventions to prevent poor outcomes.
The main objectives, of this study, was to identify the common causes of death censored graft failure among kidney transplant recipients. Knowing the causes may help provider to intervene on time and prevent for the graft loss.
This was a single-center, retrospective study among kidney transplant recipients who were transplanted at the University of Wisconsin, and who had graft failure between January 1, 2006 and December 31, 2016 and transplanted between January 1, 1994 to December 31, 2016. Patients were included if they underwent a kidney biopsy within one year prior to the graft failure. We divided histopathological causes of graft failure based on the post-transplant interval divided into 2 years interval, based on the causes of ESRD and also the types of induction immunosuppressive medication. In cases where a patient had multiple biopsy diagnoses, all diagnoses were also reported separately, although the primary diagnosis (first diagnosis) was used for the cause of graft failure.
A total of 329 kidney transplant recipients fulfilled our selection criteria and were included in the study. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant. Most early graft failures within the first six years of transplant are related to AR and are in theory preventable. Similarly, more effective diagnostic, monitoring, and therapeutic strategies for TG and IFTA are needed to improve long-term graft survival.
In this study of the cause of graft failure among kidney transplant recipients, we found that the primary cause of graft failure varies with time after transplantation. AR, mainly antibody-mediated rejection (ABMR), was the most common cause of graft failure and accounted for 40% of graft failures, which peaked at 6 years post-transplant. After an AR, TG, one of the most specific histological findings of chronic ABMR, accounted for 17% of graft failure, which occurred mainly after 6-7 years post-transplant and was the most common cause of graft failure and even surpassed AR as a cause of graft failure. Interestingly, calcineurin inhibitor toxicity was not a common cause of graft failure.
Further studies in this field and specifically effective treatment of AR is needed to prolong the graft survival. Most of the work is being conducted in the fields of prevention and treatment of AR, and in time we may be able to effectively manage AR including acute ABMR. However, chronic changes and the lesser understood mechanisms of TG and IFTA may hinder our aim of prolonged graft survival and study should focus on the field of prevention or treatment of TG and IFTA.