Endothelial dysfunction and oxidative stress in chronic renal failure.
Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.
Ghiadoni
Lorenzo
L
Department of Internal Medicine, University of Pisa, Pisa, Italy. l.ghiadoni@med.unipi.it
Cupisti
Adamasco
A
Huang
Yale
Y
Mattei
Paola
P
Cardinal
Heloise
H
Favilla
Stefania
S
Rindi
Paolo
P
Barsotti
Giuliano
G
Taddei
Stefano
S
Salvetti
Antonio
A
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology; D001916:Brachial Artery; D016022:Case-Control Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000628:therapy*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011994:Recombinant Proteins; D012016:Reference Values; D006435:Renal Dialysis / Q000379:methods; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014664:Vasodilation / Q000502:physiology
D000959:Antihypertensive Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D001205:Ascorbic Acid