Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients.

Ferrari, Paolo; Schroeder, Verena; Anderson, Suzanne; Kocovic, Leonardo; Vogt, Bruno; Schiesser, Daniela; Marti, Hans-Peter; Ganz, Reinhold; Frey, Felix J; Kohler, Hans P (2002). Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation, 74(8), pp. 1147-1152. Lippincott Williams & Wilkins 10.1097/01.TP.0000035848.73883.1B

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BACKGROUND The mechanism of avascular osteonecrosis (AVN) is controversial. Besides an increased bone marrow pressure with reduced blood supply, an enhanced coagulation has been considered. We hypothesize that a genetic variant of the plasminogen activator inhibitor-1 (PAI-1) determines the risk of AVN in glucocorticoid-treated patients. METHODS Genotyping for the 4G/5G PAI-1 polymorphism was performed in 228 glucocorticoid-treated renal transplant patients. AVN of the hip was present in 26 patients. Magnetic resonance imaging (MRI) of the hips was obtained in 81 of the remaining renal transplant patients without clinical symptoms of AVN. RESULTS The presence of the homozygous 4G/4G PAI-1 genotype was higher in patients with AVN (60.3%) as compared with patients without either clinical (20.6%, P<0.007) or radiological signs of AVN (17.3%, P<0.002). The prevalence of AVN by genotype was 1.8% with the 5G/5G, 7.7% with the 5G/4G, and 30.3% with the 4G/4G alleles (P<0.001 vs. 5G/4G and 5G/5G). The prevalence of AVN increased with increasing body mass index (BMI) (P=0.04). The prevalence of AVN by genotype in subjects with persistent hyperparathyroidism was 4.2% with the 5G/5G, 15.2% with the 5G/4G, and 55.5% with the 4G/4G alleles (P<0.003 vs. 5G/4G and P<0.001 vs. 5G/5G). CONCLUSIONS Hypofibrinolysis conferred by the 4G/4G PAI-1 gene variant is a major predisposing factor for AVN in renal transplant patients. The risk is particularly high in obese subjects or patients with persistent hyperparathyroidism. A prospective intervention study of early anticoagulation after renal transplantation is needed to assess whether glucocorticoid-associated AVN can be prevented.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Experimentelle Hämostase

UniBE Contributor:

Schröder, Verena; Anderson, Suzanne E. and Vogt, Bruno

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0041-1337

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Bruno Vogt

Date Deposited:

07 Jan 2020 13:05

Last Modified:

07 Jan 2020 13:10

Publisher DOI:

10.1097/01.TP.0000035848.73883.1B

PubMed ID:

12438962

BORIS DOI:

10.7892/boris.51093

URI:

https://boris.unibe.ch/id/eprint/51093

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