Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 3:35:10071.
doi: 10.3389/ti.2021.10071. eCollection 2021.

Soluble Urokinase Receptor and Mortality in Kidney Transplant Recipients

Christian Morath  1 , Salim S Hayek  2 , Bernd Döhler  3 , Christian Nusshag  1 , Claudia Sommerer  1 , Martin Zeier  1 , Jochen Reiser  4 , Caner Süsal  3   5
Affiliations

Soluble Urokinase Receptor and Mortality in Kidney Transplant Recipients

Christian Morath et al. Transpl Int. .

Abstract

Main problem: Soluble urokinase plasminogen activator receptor (suPAR) is an immunological risk factor for kidney disease and a prognostic marker for cardiovascular events. Methods: We measured serum suPAR levels in a total of 1,023 kidney transplant recipients either before (cohort 1, n = 474) or at year 1 after transplantation (cohort 2, n = 549). The association of suPAR levels and all-cause and cardiovascular mortality was evaluated by multivariable Cox regression analysis. Results: The highest suPAR tertile compared to the two lower tertiles had a significantly higher risk of all-cause mortality in both cohorts separately (cohort 1: hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.20-3.08, p = 0.007; cohort 2: HR = 2.78, 95% CI 1.51-5.13, p = 0.001) and combined (n = 1,023, combined HR = 2.14, 95% CI 1.48-3.08, p < 0.001). The association remained significant in the subgroup of patients with normal kidney function (cohort 2: HR = 5.40, 95% CI 1.42-20.5, p = 0.013). The increased mortality risk in patients with high suPAR levels was attributable mainly to an increased rate of cardiovascular death (n = 1,023, HR = 4.24, 95% CI 1.81-9.96, p < 0.001). Conclusion: A high suPAR level prior to and at 1 year after kidney transplantation was associated with an increased risk of patient death independent of kidney function, predominantly from cardiovascular cause.

Keywords: cardiovascular; kidney; mortality; suPAR; transplantation.

PubMed Disclaimer

Conflict of interest statement

CM and MZ, together with the University of Heidelberg, are co-founders of TolerogenixX GmbH, Heidelberg, Germany, a biotechnology company that holds licenses for cell therapies. CM, CSü, and MZ filed a patent application for a cell therapy. JR is cofounder of Trisaq, a biotechnology company developing drugs targeting suPAR. SH and JR are members of the scientific advisory board of Trisaq. JR holds patents and licenses related to suPAR. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan-Meier curves demonstrating the impact of suPAR (ng/ml) on 5-year mortality post-transplant in cohort 1 (A) and after serum collection date in cohort 2 (B). The categories “Low,” “Medium,” and “High” are defined by the tertiles of suPAR in each cohort. Log rank p values for trend are shown.
FIGURE 2
FIGURE 2
Kaplan-Meier curves demonstrating the impact of suPAR (ng/ml) above the upper tertile (“High”) against suPAR values below the upper tertile (“Normal”) on 5-year mortality after serum collection date. Log rank p value is shown.
FIGURE 3
FIGURE 3
Kaplan-Meier curves demonstrating the impact of suPAR (ng/ml) on death with a functioning graft in the following 5 years after serum collection date as stratified by cause of death. Log rank p value is shown. (A) Due to CVD. (B) Due to infection. (C) Due to cancer.
FIGURE 4
FIGURE 4
Kaplan-Meier curves demonstrating the impact of suPAR (ng/ml) on 5-years mortality after serum collection date as stratified by recipient sex (A,B) and recipient age (C,D). Log rank p value is shown.
See this image and copyright information in PMC

References

    1. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the Causes of Kidney Transplant Failure: the Dominant Role of Antibody-Mediated Rejection and Nonadherence. Am J Transpl (2012). 12:388–99. 10.1111/j.1600-6143.2011.03840.x - DOI - PubMed
    1. Opelz G, Döhler B. Association between Steroid Dosage and Death with a Functioning Graft after Kidney Transplantation. Am J Transpl (2013). 13:2096–105. 10.1111/ajt.12313 - DOI - PubMed
    1. Hayek SS, Leaf DE, Samman Tahhan A, Raad M, Sharma S, Waikar SS, et al. Soluble Urokinase Receptor and Acute Kidney Injury. N Engl J Med (2020). 382:416–26. 10.1056/nejmoa1911481 - DOI - PMC - PubMed
    1. Hayek SS, Sever S, Ko Y-A, Trachtman H, Awad M, Wadhwani S, et al. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med (2015). 373:1916–25. 10.1056/nejmoa1506362 - DOI - PMC - PubMed
    1. Slot O, Brünner N, Locht H, Oxholm P, Stephens RW. Soluble Urokinase Plasminogen Activator Receptor in Plasma of Patients with Inflammatory Rheumatic Disorders: Increased Concentrations in Rheumatoid Arthritis. Ann Rheum Dis (1999). 58:488–92. 10.1136/ard.58.8.488 - DOI - PMC - PubMed

Substances