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. 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 P-ADMA levels (604 +/- 131 versus 391 +/- 67 nmol/L; P < 0.01) and U-ADMA excretion (22 +/- 4 versus 15.2 +/- 3 nmol/Amol 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/mu mol creatinine; P < 0.01), and decreased plasma nitrite plus nitrate (P-NOx) levels (21 +/- 5 versus 32 +/- 6 mu mol/L; P < 0.01) and U-NOx excretion (59 +/- 7 versus 138 +/- 27 mu mol/mu mol creatinine; P < 0.01). Limitations: 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 CADMA and is accompanied by oxidative stress. Am J Kidney Dis 51:184-191. (c) 2008 by the National Kidney Foundation, Inc.