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. 2022 Aug;22(8):2016-2027.
doi: 10.1111/ajt.17047. Epub 2022 Apr 29.

Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality

Torbjørn Fossum Heldal  1   2   3 , Anders Åsberg  3   4   5 , Thor Ueland  2   6   7 , Anna Varberg Reisaeter  3   4 , Søren E Pischke  8   9 , Tom Eirik Mollnes  6   8   10   11 , Pål Aukrust  6   7   12 , Anders Hartmann  2   3 , Kristian Heldal  1   3 , Trond Jenssen  2   3
Affiliations

Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality

Torbjørn Fossum Heldal et al. Am J Transplant. 2022 Aug.

Abstract

In the general population, low-grade inflammation has been established as a risk factor for all-cause mortality. We hypothesized that an inflammatory milieu beyond the time of recovery from the surgical trauma could be associated with increased long-term mortality in kidney transplant recipients (KTRs). This cohort study included 1044 KTRs. Median follow-up time post-engraftment was 10.3 years. Inflammation was assessed 10 weeks after transplantation by different composite inflammation scores based on 21 biomarkers. We constructed an overall inflammation score and five pathway-specific inflammation scores (fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, leukocyte activation). Mortality was assessed with Cox regression models adjusted for traditional risk factors. A total of 312 (29.9%) patients died during the follow-up period. The hazard ratio (HR) for death was 4.71 (95% CI: 2.85-7.81, p < .001) for patients in the highest quartile of the overall inflammation score and HRs 2.35-2.54 (95% CI: 1.40-3.96, 1.52-4.22, p = .001) for patients in the intermediate groups. The results were persistent when the score was analyzed as a continuous variable (HR 1.046, 95% CI: 1.033-1.056, p < .001). All pathway-specific analyses showed the same pattern with HRs ranging from 1.19 to 2.70. In conclusion, we found a strong and consistent association between low-grade systemic inflammation 10 weeks after kidney transplantation and long-term mortality.

Keywords: donors and donation: donation after circulatory death (DCD); editorial/personal viewpoint; ethics; ethics and public policy; law/legislation; organ perfusion and preservation; organ procurement; organ procurement and allocation; solid organ transplantation.

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Figures

FIGURE 1
FIGURE 1
Kaplan‐Meier plots showing the association between the overall inflammation score and all‐cause mortality. Log‐rank test: p < .001
FIGURE 2
FIGURE 2
Kaplan‐Meier plot showing the association between pathway‐specific inflammation scores and long‐term all‐cause mortality. (A) Fibrogenesis score and mortality. Log‐rank: p < .001. (B) General/vascular inflammation score and mortality. Log‐rank: p < .001. (C) Metabolic inflammation score and mortality. Log‐rank: p < .001. (D) Growth/angiogenesis score and mortality. Log‐rank: p < .001. (E) Leukocyte activation score and mortality. Log‐rank: p < .001
FIGURE 3
FIGURE 3
Kaplan‐Meier plot showing the association between the post‐hoc predictive inflammation score and all‐cause mortality. Log‐rank test: p < .001
See this image and copyright information in PMC

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