title: Decreased paraoxonase 1 (PON1) lactonase activity in hemodialyzed and renal transplanted patients. A novel cardiovascular biomarker in end-stage renal disease.
abstract: BACKGROUND
  Human paraoxonase-1 (PON1) has also been described as a lactonase. Decreased PON1 lactonase activity was found to be a predictor of cardiovascular disease. Homocysteine thiolactonase activity may prevent proteins from homocysteinylation and is thought to be a protective factor against the progression of atherosclerosis. Previous studies have demonstrated decreased PON1 paraoxonase activity in hemodialyzed (HD) and renal transplant (TRX) patients; however, lactonase activity has not been investigated. We aimed to determine the paraoxonase and lactonase activities and to clarify the relationship between lactonase activity and a set of cardiovascular risk factors, such as homocysteine, cystatin C and asymmetric dimethylarginine (ADMA) levels, in HD and TRX patients and in healthy controls.
  
  
  METHODS
  One hundred and eight HD and 78 TRX patients and 63 healthy controls were involved in the study. Paraoxonase and lactonase activities (paraoxon and gamma-thiobutyrolactone as substrates) were measured spectrophotometrically. ADMA level was determined with sandwich enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Both HD and TRX patients had significantly lower lactonase activities compared to the control group (P<0.05). Significantly lower paraoxonase activities were found in HD patients compared to the TRX group (P<0.05). Significant negative correlation was found between lactonase activity and ADMA level in the whole study population (P<0.001), while paraoxonase and lactonase activities showed significant positive correlation (P<0.001). Multiple regression analysis identified paraoxonase activity and homocysteine level as independent predictors of lactonase activity.
  
  
  CONCLUSIONS
  Lactonase activity is a potential new predictor of cardiovascular risk in renal failure. Measurement of lactonase activity is recommended in future studies on HD and TRX patients.
authors.affiliation: First Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sztanek
authors.forename: Ildikó
authors.initials: I
authors.lastname: Seres
authors.forename: Mariann
authors.initials: M
authors.lastname: Harangi
authors.forename: Lajos
authors.initials: L
authors.lastname: Lőcsey
authors.forename: János
authors.initials: J
authors.lastname: Padra
authors.forename: György J R
authors.initials: GJ
authors.lastname: Paragh
authors.forename: László
authors.initials: L
authors.lastname: Asztalos
authors.forename: György
authors.initials: G
authors.lastname: Paragh
mesh_terms: D043303:Aryldialkylphosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000201:enzymology* / Q000209:etiology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000201:enzymology* / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D006435:Renal Dialysis / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human