Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease.
BACKGROUND
Patients with autosomal dominant polycystic kidney disease (ADPKD) with normal renal function have endothelial dysfunction and decreased nitric oxide synthase activity in subcutaneous resistance vessels. We investigated asymmetric dimethylarginine (ADMA) as a marker of an inhibitor of nitric oxide synthase and the lipid peroxidation product 13-hydroxyoctadecadienoic acid (HODE) as a marker of oxidative stress in patients with early ADPKD.


METHODS
Cross-sectional study.


METHODS
Patients with early ADPKD (n = 27) and age-matched volunteers (n = 30) from a single academic medical center.


METHODS
Patients with ADPKD versus controls.


METHODS
Plasma (P) levels, urinary (U) excretion, and urinary clearance (C) of ADMA and HODE. Because of multiple comparisons, P for significance is considered less than 0.0167.


RESULTS
Patients with ADPKD had significantly increased P(ADMA) levels (604 +/- 131 versus 391 +/- 67 nmol/L; P < 0.01) and U(ADMA) excretion (22 +/- 4 versus 15.2 +/- 3 nmol/micromol creatinine; P = 0.01), decreased C(ADMA) (25 +/- 3 versus 33 +/- 4 mL/min; P = 0.01), increased P(HODE) levels (316 +/- 64 versus 230 +/- 38 nmol/L; P < 0.01) and U(HODE) excretion (467 +/- 67 versus 316 +/- 40 nmol/micromol creatinine; P < 0.01), and decreased plasma nitrite plus nitrate (P(NOx)) levels (21 +/- 5 versus 32 +/- 6 micromol/L; P < 0.01) and U(NOx) excretion (59 +/- 7 versus 138 +/- 27 micromol/micromol creatinine; P < 0.01).


CONCLUSIONS
Small sample size, cross-sectional nature of study, and limited number of markers of oxidative stress.


CONCLUSIONS
P(ADMA) and P(HODE) levels are increased in patients with early ADPKD. Increased P(ADMA) level is related to decreased C(ADMA) and is accompanied by oxidative stress.
Wang
Dan
D
Cardiovascular-Kidney-Hypertension Institute, Division of Nephrology and Hypertension and Angiogenesis Section, Lombardi Cancer Institute, Georgetown University, Washington, DC 20007, USA. dw32@georgetown.edu
Strandgaard
Svend
S
Borresen
Malene L
ML
Luo
Zaiming
Z
Connors
Stephanie G
SG
Yan
Qing
Q
Wilcox
Christopher S
CS
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008041:Linoleic Acids / Q000097:blood* / Q000652:urine*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; D004791:Enzyme Inhibitors; D008041:Linoleic Acids; D009569:Nitric Oxide; C024348:13-hydroxy-9,11-octadecadienoic acid; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase