Asymmetric Dimethylarginine and Lipid Peroxidation Products in Early Autosomal Dominant Polycystic Kidney Disease
Received 4 April 2007; accepted 27 September 2007. published online 03 January 2008.
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.
Study Design
Cross-sectional study.
Setting & Participants
Patients with early ADPKD (n = 27) and age-matched volunteers (n = 30) from a single academic medical center.
Factor
Patients with ADPKD versus controls.
Outcomes & Measurement
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 PADMA levels (604 ± 131 versus 391 ± 67 nmol/L; P < 0.01) and UADMA excretion (22 ± 4 versus 15.2 ± 3 nmol/μmol creatinine; P = 0.01), decreased CADMA (25 ± 3 versus 33 ± 4 mL/min; P = 0.01), increased PHODE levels (316 ± 64 versus 230 ± 38 nmol/L; P < 0.01) and UHODE excretion (467 ± 67 versus 316 ± 40 nmol/μmol creatinine; P < 0.01), and decreased plasma nitrite plus nitrate (PNOx) levels (21 ± 5 versus 32 ± 6 μmol/L; P < 0.01) and UNOx excretion (59 ± 7 versus 138 ± 27 μmol/μmol creatinine; P < 0.01).
Limitations
Small sample size, cross-sectional nature of study, and limited number of markers of oxidative stress.
Conclusions
PADMA and PHODE levels are increased in patients with early ADPKD. Increased PADMA level is related to decreased CADMA and is accompanied by oxidative stress.
1Cardiovascular-Kidney-Hypertension Institute, Division of Nephrology and Hypertension and Angiogenesis Section, Lombardi Cancer Institute, Georgetown University, Washington, DC
2Department of Nephrology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
3Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, MD.
Address correspondence to Dan Wang, MD, PhD, 4000 Reservoir Rd NW, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007.
ABSTRACT