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Genetic and metabolic determinants of increased plasma plasminogen activator inhibitor-1 activity in children with renal transplants

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Abstract

Recent studies have shown that activity of plasminogen activator inhibitor-1 (PAI-1), a prothrombotic protein, may be increased in transplanted patients. The aim of the present investigation was to determine PAI-1 activity in pediatric recipients of renal transplants and to establish the relative contribution of both genetic and metabolic factors. In 29 children and adolescents with stable renal transplants, we related plasma PAI-1 activity to an indicator of inflammatory status [plasma concentration of C-reactive protein (CRP)] and to elements of the insulin resistance syndrome [body mass index (BMI), fasting insulinemia, HOMA index and plasma triglyceride, HDL-cholesterol, apolipoproteins A-1 and B concentrations]. Polymorphisms of PAI-1, apolipoprotein E (apoE) and angiotensin-converting enzyme (ACE) genes were also investigated. In all patients the study was repeated 1 year later. PAI-1 activity remained constantly elevated (23.4±22.8 and 18.6±7.8 U/ml in the first and second study, respectively, P=NS). Plasma PAI-1 activity correlated positively with CRP (P=0.001), BMI z score (P=0.02), fasting insulinemia (P=0.009), and HOMA index (P=0.006). No significant correlations were found in this population between plasma PAI-1 activity and age, gender, time elapsed after transplantation and plasma homocysteine, total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma PAI-1 activity was not related to the cumulative dose of prednisone, cyclosporin A, or tacrolimus. Plasma PAI-1 activity was significantly higher in 5 children with apoE3/apoE4 genotype. No apparent influences of the PAI-1 4G/4G and ACE I/D genotypes were observed. In a multiple stepwise regression model, fasting insulinemia and apoE3/apoE4 genotype accounted for 45% of the observed plasma PAI-1 variability. We conclude that increased PAI-1 activity in children with stable renal transplants is determined both by genetic factors and by metabolic factors, the latter mainly linked to the insulin resistance syndrome.

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Acknowledgement

This study was partly supported by a grant (01/1452) from the Fondo de Investigación Sanitaria, Spanish Ministry of Health (P. Sanjurjo).

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Authors and Affiliations

  1. Division of Biochemistry, Department of Pediatrics, Hospital de Cruces and Basque University School of Medicine, Bilbao, País Vasco, Spain

    Pilar Gimeno & Miguel Rueda

  2. Division of Metabolism, Department of Pediatrics, Hospital de Cruces and Basque University School of Medicine, Bilbao, País Vasco, Spain

    Luis Aldámiz-Echevarría, Pablo Sanjurjo, Gustavo Pérez-Nanclares & José Ignacio Ruiz

  3. Division of Nephrology, Department of Pediatrics, Hospital de Cruces and Basque University School of Medicine, Bilbao, País Vasco, Spain

    Alfredo Vallo, Mireia Aguirre & Juan Rodríguez-Soriano

  4. Department of Pediatrics, Hospital de Cruces, Plaza de Cruces s/n, 48903 Vizcaya, Baracaldo, Spain

    Juan Rodríguez-Soriano

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  1. Luis Aldámiz-Echevarría
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  2. Pablo Sanjurjo
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Correspondence to Juan Rodríguez-Soriano.

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Aldámiz-Echevarría, L., Sanjurjo, P., Vallo, A. et al. Genetic and metabolic determinants of increased plasma plasminogen activator inhibitor-1 activity in children with renal transplants. Pediatr Nephrol 18, 749–755 (2003). https://doi.org/10.1007/s00467-003-1157-6

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  • DOI: https://doi.org/10.1007/s00467-003-1157-6

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