Endostatin Is an Independent Risk Factor of Graft Loss after Kidney Transplant.


Journal

American journal of nephrology
ISSN: 1421-9670
Titre abrégé: Am J Nephrol
Pays: Switzerland
ID NLM: 8109361

Informations de publication

Date de publication:
2020
Historique:
received: 10 02 2020
accepted: 09 04 2020
pubmed: 23 4 2020
medline: 27 5 2021
entrez: 23 4 2020
Statut: ppublish

Résumé

Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71-0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19-31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.

Sections du résumé

BACKGROUND
Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown.
METHODS
We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA.
RESULTS
Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71-0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19-31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality.
CONCLUSION
Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.

Identifiants

pubmed: 32320989
pii: 000507824
doi: 10.1159/000507824
doi:

Substances chimiques

Biomarkers 0
Endostatins 0

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

373-380

Informations de copyright

© 2020 S. Karger AG, Basel.

Auteurs

Chang Chu (C)

Department of Nephrology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Ahmed A Hasan (AA)

Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

Mohamed M S Gaballa (MMS)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Faculty of Veterinary Medicine, Benha University, Toukh, Egypt.

Shufei Zeng (S)

Department of Nephrology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Yingquan Xiong (Y)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.

Saban Elitok (S)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Department of Nephrology and Endocrinology/Diabetology, Klinikum Ernst von Bergmann, Potsdam, Germany.

Bernhard K Krämer (BK)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.

Berthold Hocher (B)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany, berthold.hocher@medma.uni-heidelberg.de.
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China, berthold.hocher@medma.uni-heidelberg.de.
Institute of Medical Diagnostics, IMD Berlin, Berlin, Germany, berthold.hocher@medma.uni-heidelberg.de.

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