Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Oct 28, 2019; 9(6): 123-133
Published online Oct 28, 2019. doi: 10.5500/wjt.v9.i6.123
Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression
Sandesh Parajuli, Fahad Aziz, Neetika Garg, Sarah E Panzer, Emily Joachim, Brenda Muth, Maha Mohamed, Justin Blazel, Weixiong Zhong, Brad C Astor, Didier A Mandelbrot, Arjang Djamali
Sandesh Parajuli, Fahad Aziz, Neetika Garg, Sarah E Panzer, Emily Joachim, Brenda Muth, Maha Mohamed, Justin Blazel, Brad C Astor, Didier A Mandelbrot, Arjang Djamali, Division of Nephrology, Department of Medicine, University of Wisconsin, Madison, WI 53705, United States
Weixiong Zhong, Department of Pathology, University of Wisconsin, Madison, WI 53705, United States
Brad C Astor, Department of Population Health Sciences, University of Wisconsin, Madison, WI 53705, United States
Arjang Djamali, Division of Transplantation, Department of Surgery, University of Wisconsin, Madison, WI 53705, United States
Author contributions: Parajuli S and Djamali S had an original idea, designed the study, analyzed the data, prepared the manuscript; Aziz F, Garg N, Panzer SE, Joachim E, Muth B, Mohamed M, Blazel J, Zhong W, Astor BC, and Mandelbrot DA analyzed the data and edited the manuscript.
Institutional review board statement: This study was approved by the Health Sciences Institutional Review Board at the University of Wisconsin.
Informed consent statement: Waiver of informed consent obtained due to: (1) The study involves no more than minimal risk to the subjects; (2) The waiver will not adversely affect the rights and welfare of the subjects; (3) The study could not practicably be carried out without the waiver.
Conflict-of-interest statement: The authors have no financial disclosures.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sandesh Parajuli, MBBS, MBBS, MD, Assistant Professor, Division of Nephrology, Department of Medicine, University of Wisconsin, 4175 UW Medical Foundation Centennial Building, 1685 Highland Avenue, Madison, WI 53705, United States. sparajuli@medicine.wisc.edu
Telephone: +1-608-2650152
Received: June 6, 2019
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
Abstract
BACKGROUND

The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.

AIM

To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.

METHODS

In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.

RESULTS

We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. 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.

CONCLUSION

In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Keywords: Kidney biopsy, Acute rejection, Graft failure, Transplant glomerulopathy, Interstitial fibrosis and tubular atrophy

Core tip: There have been significant improvements in early graft survival. However, long-term graft survival has only had modest improvement. Causes of “true” late kidney allograft failure remain unclear. In this study, we explored the causes of graft failure based on the various factors, which may allow providers to determine interventions to prevent poor outcomes. We found, acute rejection, mainly antibody-mediated rejection, was the most common cause of early graft failure. And transplant glomerulopathy was a common cause of late graft failure, which occurred mainly after 6-7 years post-transplant even surpassed acute rejection.