Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Abstract

Background: Biopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.

Methods: Patients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18-39 years (young), 40-55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.

Results: Rejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).

Conclusion: Rejection is a major cause of graft loss but recipient's age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.

Keywords: ABMR; TCMR; antibody-mediated rejection; graft failure risk; kidney transplantation; long term.

FIGURE 1

Recipients of a kidney transplant between 1995 and 2005 and causes of graft loss within the first year after transplantation. Numbers of recipients in the different age groups after 1 year are shown and the numbers lost at 25 years follow-up thereafter.

FIGURE 2

Kaplan-Meier analysis of graft survival for different age groups. The top figure (A) shows uncensored graft survival, the middle figure (B) shows the loss of grafts because of death with functioning graft and the bottom figure (C) shows the graft survival censored for death. P-values < 0.05 obtained by pooled over strata in the upper and middle figure are shown. In the lower figure (C), the p-value for difference by log rank test statistics comparing the elderly group with the young or middle age group is given. The numbers of recipients in follow-up at different time points after transplantation are shown below the figure.

FIGURE 3

Pie charts are given for causes of graft loss in different age groups in different time periods after transplantation starting from 1 year after transplantation. In part (A), the categories of cause for graft loss represent death with functioning graft, unknown (no biopsy performed and no clinical diagnosis), a clinical diagnosis of kidney injury or disease, and kidney biopsy-based cause of graft loss. In part (B), the category of kidney biopsy-based cause of graft loss is split into TCMR, ABMR, return original disease, and de novo kidney disease. The numbers of graft loss and recipients lost at follow-up within every post-transplantation period are shown above the pie charts. Every row of pie chart represents a recipient age category at the time of transplantation (18–39, 40–55, and > 55 years) and every column represents a time period after transplantation (1–5, 5–15, and > 15 years after transplantation).

FIGURE 4

Kaplan-Meier analysis of the antibody mediated (ABMR) and T cell mediated rejection (TCMR) free-survival and the ABMR and TCMR-related graft loss for different age groups. The lower panel right shows the interstitial fibrosis and tubular atrophy (IFTA) related graft loss with a subgroup analysis for recipients with and without previous TCMR. All analysis were done by censoring for death and lost at follow-up. Number of patients in follow-up per age stratum is shown below the graphs. Only p-values < 0.05 are shown in the figures and obtained by log rank test statistics pooled over strata (TCMR-free graft survival), comparing the young group with the other elderly group (TCMR-related graft loss), and pairwise over strata (TCMR and IFTA-related graft loss).

FIGURE 5

Kaplan-Meier analysis of the antibody mediated (ABMR) rejection free-survival for recipients with (n = 159) and without (n = 573) presence of pretransplant donor-specific antibodies against HLA (DSA). The p-value shown is obtained by comparing different strata with long rank test statistics.

FIGURE 6

Kaplan-Meier analysis of the antibody mediated (ABMR) rejection free-survival for recipients with (n = 207) and without (n = 530) a previous episode of TCMR. The p-value shown is obtained by comparing different strata with long rank test statistics.