title: Hyperhomocysteinemia and protein damage in chronic renal failure and kidney transplant pediatric patients--Italian initiative on uremic hyperhomocysteinemia (IIUH).
abstract: BACKGROUND
  Plasma homocysteine, a new cardiovascular risk factor in both children and adults, is higher in chronic renal failure or kidney transplant patients. This alteration has been linked, in chronic renal failure, to plasma protein damage, represented by increased L-isoaspartyl residues. We measured plasma homocysteine levels and plasma protein damage in pediatric patients from four different Italian regions with conservatively treated renal failure; hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or transplants, to establish the presence of protein damage and the relative role of hyperhomocysteinemia.
  
  
  METHODS
  High performance liquid chromatography (HPLC) separation measured total plasma homocysteine levels, using precolumn derivatization with ammonium 7-fluorobenzo-2-oxa-1, 3-diazole-4-sulphonate (SBD-F). Plasma protein L-isoaspartyl residues were quantitated using human recombinant protein carboxyl methyl transferase (PCMT).
  
  
  RESULTS
  In all patient groups, homocysteine levels were significantly higher with respect to the control (Control: 6.87 +/- 0.73 microM) conservatively treated, 14.19 +/- 1.73 microM; hemodialysis, 27.03 +/- 4.32 microM; CAPD, 22.38 +/- 3.73 microM; transplanted, 20.22 +/- 2.27 microM, p < 0.001 vs. control]. Plasma protein damage was significantly higher in conservatively treated, hemodialysis (HD) and CAPD patients, while in transplant patients it was no different from the control.
  
  
  CONCLUSIONS
  We concluded that in pediatric patients of different Italian geographical origin, plasma homocysteine levels were significantly higher in all groups with respect to healthy children; therefore contributing to the elevated cardiovascular risk present in these patients. Plasma protein L-isoaspartyl content was higher in renal failure patients, but kidney transplant patients had normal levels, indicating that this kind of protein damage relates more to the toxic action of uremic retention solutes, than to plasma homocysteine levels.
authors.affiliation: Division of Nephrology, Department of Pediatrics, Second University of Naples (SUN), School of Medicine and Surgery, Naples, Italy. alessandra.perna@unina2.it
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
authors.forename: Daniela
authors.initials: D
authors.lastname: Molino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Galletti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.forename: Graziella
authors.initials: G
authors.lastname: Zacchello
authors.forename: Rosa
authors.initials: R
authors.lastname: Bellantuono
authors.forename: Angela
authors.initials: A
authors.lastname: Caringella
authors.forename: Carmelo
authors.initials: C
authors.lastname: Fede
authors.forename: Roberto
authors.initials: R
authors.lastname: Chimenz
authors.forename: Natale G
authors.initials: NG
authors.lastname: De Santo
mesh_terms: D017677:Age Distribution; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000032:analysis; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects* / Q000379:methods; D011446:Prospective Studies; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis
chemical_list: D001798:Blood Proteins; D003404:Creatinine