Enhanced plasma levels of advanced glycation end products (AGE) and pro-inflammatory cytokines in children/adolescents with chronic renal insufficiency and after renal replacement therapy by dialysis and transplantation--are they inter-related?
OBJECTIVE
Advanced glycation end products (AGEs) are formed by non-enzymatic glycation or glycoxidation. After their interaction with specific receptors, they may induce expression of various proinflammatory cytokines. AGEs were shown to accumulate with advanced age, in diabetes mellitus and, in particular, in patients with chronic renal failure. In contrast to numerous investigations in adults, there are no data on plasma levels of AGEs in children with chronic renal insufficiency (CRI) and after renal replacement therapy. To elucidate the specific role of renal impairment for the formation of AGEs, these data become especially interesting by exclusion of the age-dependent modulatory effects occurring in adults. Therefore, we investigated the concentrations of fluorescent (FL) AGEs, carboxymethyllysine (CML) and markers of inflammation (CRP, IL-6, TNF-alpha) in children/adolescents with chronic renal insufficiency (CRI) and on renal replacement therapy with maintenance dialysis (D) or renal transplantation (TX).


METHODS
Eleven CRI patients on conservative treatment (CRI, age: mean 12.6, median 12.80, SD 5.8 +/- 1.7 years, serum creatinine: 205.7, 157.5, 58.0 micromol/l, respectively), 10 patients on D (13.6, 13.0, 5.4 years, and 698.2, 633.8, 296.1 micromol/l, respectively) and 9 patients after TX (15.9, 16.0, 3.4 years, and 115.9, 128.0, 35.1 micromol/l, respectively) were included.


METHODS
Plasma levels of CML, TNF-alpha, and IL-6 were determined by ELISA, FL-AGEs spectrofluorimetrically (lambda(ex)/lambda(em): 370/440 nm).


RESULTS
FL-AGEs and CML levels were increased in all 3 groups with the highest levels in the D patients, a successful renal transplantation did not lead to normalization of plasma AGEs. The mean CRP and IL-6 concentrations were marginally elevated, and no significance among groups was revealed. TNF-alpha was noticeably elevated in all groups, with the highest values in CRI and TX patients, while in the dialysis patients the rise was less pronounced. Stepwise multiple regression did not reveal any correlation between AGEs and proinflammatory parameters, even after exclusion of the TX group from analysis.


CONCLUSIONS
In children with CRI and on maintenance dialysis therapy, plasma AGE levels are markedly increased. After renal transplantation, AGE levels decrease without normalization. Proinflammatory parameters (except for TNF-alpha) are only mildly to moderately elevated. No association between AGE levels and data characterizing a proinflammatory state was revealed.
Sebeková
K
K
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia. sebekova@upkm.sk
Podracká
L
L
Heidland
A
A
Schinzel
R
R
D000293:Adolescent; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein