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Review
. 2015 Jan;26(1):20-9.
doi: 10.1681/ASN.2014040378. Epub 2014 Aug 5.

Through a glass darkly: seeking clarity in preventing late kidney transplant failure

Mark D Stegall  1 , Robert S Gaston  2 , Fernando G Cosio  3 , Arthur Matas  4
Affiliations
Review

Through a glass darkly: seeking clarity in preventing late kidney transplant failure

Mark D Stegall et al. J Am Soc Nephrol. 2015 Jan.

Abstract

A common lament is that long-term kidney transplant outcomes remain the same despite improvements in early graft survival. To be fair, progress has been made-in both our understanding of chronic injury and modestly, graft survival. However, we are still a long way from actually solving this important and difficult problem. In this review, we outline recent data supporting the existence of several causes of renal allograft loss, the incidences of which peak at different time points after transplantation. On the basis of this broadened concept of chronic renal allograft injury, we examine the challenges of clinical trial design in long-term studies, including the use of surrogate end points and biomarkers. Finally, we suggest a path forward that, ultimately, may improve long-term renal allograft survival.

Keywords: chronic allograft failure; clinical trial; immunosuppression; kidney transplantation; renal transplantation; transplant pathology.

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Figures

Figure 1.
Figure 1.
Rates of late renal allograft loss have remained constant. (A) Kaplan–Meier cumulative graft failure and (B) death-censored graft failure by year of first deceased SCD transplants from transplant years 1989–2008. Reprinted from ref. , with permission.
Figure 2.
Figure 2.
Changes in renal function after kidney transplantation. MDRD, Modification of Diet in Renal Disease. Reprinted from ref. , with permission. T12, 1 year; TLast, Time of last follow-up (mean 6.5 years); Q, quintile, patients were divided into quintiles based on their change in GFR over time.
Figure 3.
Figure 3.
Causes of graft loss after kidney transplantation on the basis of surveillance biopsies. Reprinted from ref. , with permission.
Figure 4.
Figure 4.
Relationship between DSA and C4d+ staining and graft survival in biopsies for cause. Reprinted from ref. , with permission.
Figure 5.
Figure 5.
Causes of graft loss over time in biopsies for cause. Reprinted from ref. , with permission.
See this image and copyright information in PMC

References

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