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/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).

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 C(ADMA) and is accompanied by oxidative stress.