Association between biomarkers of carbonyl stress with increased systemic inflammatory response in different stages of chronic kidney disease and after renal transplantation.
BACKGROUND
Chronic kidney disease (CKD) is characterized by progressive kidney dysfunction accompanied by accumulation of uremic toxins and a potential disequilibrium between the redox status and the generation of prooxidants, resulting in oxidative stress and chronic inflammation which is associated with complications (particularly cardiovascular disease) in this population. We aimed to analyze the concentration of total plasma thiols (indicator of antioxidant capacity) and the protein carbonyl content (a marker of carbonyl stress) in relation to kidney function and inflammation in a group of patients with CKD.


METHODS
A group of 68 patients with CKD (stages 2-5; mean age 57 ± 12 years, 46% male, 34% diabetics) and another group of 21 patients who underwent living donor kidney transplantation (mean age 36 ± 17 years, 50% male, 10% diabetics, and 9 ± 2 months after renal transplantation) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods, respectively, and were adjusted to the plasma albumin concentrations. Plasma levels of fibrinogen and C-reactive protein (CRP) were measured by routine methods and used as markers of inflammation.


RESULTS
Mean glomerular filtration rate (GFR) was 48 ml/min, and there was a positive correlation between GFR and thiol (r = 0.25, p < 0.05) and a negative correlation between GFR and carbonyl (r = -0.26, p < 0.05), fibrinogen (r = -0.45, p < 0.0001) and CRP (r = -0.14, p = ns). Carbonyl strongly correlated with CRP (0.49, p < 0.0001) and fibrinogen (0.30, p < 0.01). There was a significant reduction in plasma carbonyl after renal transplantation (1.4 ± 0.4 nmol/mg albumin), compared with the levels before the procedure (2.0 ± 1.4 nmol/mg albumin, p < 0.05), which parallels an improvement in thiol levels (15 ± 4 vs. 21 ± 5 nmol/mg albumin, p < 0.001). In addition, there was a significant correlation between CRP and carbonyl after the transplantation (r = 0.65; p < 0.005).


CONCLUSIONS
We observed that patients with CKD present an altered redox status and increased signs of carbonyl stress and inflammatory activity as kidney function deteriorates, which was partially but significantly improved after renal transplantation. These findings indicate the importance of renal function in the complications of CKD related to oxidative stress and inflammation.
Aveles
Paulo R
PR
Center for Health and Biological Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil.
Criminácio
Ciro R
CR
Gonçalves
Simone
S
Bignelli
Alexandre T
AT
Claro
Ligia Maria
LM
Siqueira
Sérgio S
SS
Nakao
Lia S
LS
Pecoits-Filho
Roberto
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D016030:Kidney Transplantation / Q000639:trends*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000097:blood*; D013997:Time Factors; D055815:Young Adult
D015415:Biomarkers; D018836:Inflammation Mediators; D013438:Sulfhydryl Compounds