dinoprost and Polycystic-Kidney--Autosomal-Dominant

In experimental models of polycystic kidney disease impaired bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative stress markers at the kidney level was noted. However, clinical studies investigating the potential role of endothelial dysfunction and oxidative stress in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase inhibitor as well as 15-F2t-Isoprostane and oxidized-low density lipoprotein (oxidized-LDL) as measures of oxidative stress in patients with early stages ADPKD.. We recruited 26 ADPKD patients (Group A) with modestly impaired renal function (eGFR 45-70 ml/min/1.73 m(2)), 26 age- and sex-matched ADPKD patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73 m(2)), and 26 age- and sex-matched controls (Group C). Determination of circulating levels of ADMA, 15-F2t-Isoprostane, oxidized-LDL and routine biochemistry was performed.. Group A and B had significantly higher ADMA levels as compared to controls (1.68 ± 0.7 vs 0.51 ± 0.2 μmol/l, P<0.001 and 1.26 ± 0.7 vs 0.51 ± 0.2 μmol/l, P<0.001, respectively). 15-F2t-IsoP and oxidized-LDL levels were also significantly higher in Group B relative to controls (788.8 ± 185.0 vs 383.1 ± 86.0 pgr/ml, P<0.001 and 11.4 ± 6.6 vs 6.4 ± 2.6 EU/ml, P<0.05 respectively) and were further elevated in Group A. In correlation analysis, ADMA levels exhibited strong associations with levels of 15-F2t-Isoprostane (r=0.811, P<0.001) and oxidized-LDL (r=0.788, P<0.001), whereas an inverse correlation was evident between ADMA and eGFR (r=-0.460, P<0.001).. This study shows elevation in circulating levels of ADMA along with aggravation of oxidative stress from the early stages of ADPKD. © 2014 S. Karger AG, Basel.

Topics: Adolescent; Adult; Aged; Arginine; Dinoprost; Disease Progression; Female; Glomerular Filtration Rate; Humans; Isoprostanes; Kidney Function Tests; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Young Adult

Most deaths in autosomal dominant polycystic kidney disease (ADPKD) are attributable to cardiovascular disease (CVD). We examined novel CVD biomarkers in different stages of ADPKD.. We recruited 50 hypertensive subjects with ADPKD with estimated GFR (eGFR) of >60 ml/min per 1.73 m(2); 52 hypertensive subjects with ADPKD with eGFR of 25 to 60 ml/min per 1.73 m(2); 42 normotensive subjects with ADPKD and eGFR of >60 ml/min per 1.73 m(2); and 50 healthy controls. We assayed serum C-reactive protein and IL-6 as markers of inflammation; plasma 8-epi-prostaglandin F(2α (8-epi-PGF2α)) and superoxide dismutase (SOD) as markers of oxidative stress; and homeostasis model assessment (HOMA) as a measure of insulin resistance.. The hypertensive ADPKD eGFR of 25 to 60 group had higher levels of C-reactive protein and IL-6 than controls, normotensive ADPKD with eGFR of >60, and hypertensive ADPKD with eGFR of >60. The normotensive ADPKD eGFR >60, hypertensive ADPKD eGFR >60, and hypertensive ADPKD eGFR 25 to 60 groups had higher 8-epi-PGF(2α) and lower SOD than controls, with no difference between the ADPKD groups. There was no difference in HOMA levels between any of the groups. Adjustment for age, race, gender, and body mass index did not alter these relationships.. Inflammation and oxidative stress are evident early in ADPKD even with preserved kidney function. Inflammation exhibits a graded relationship with levels of kidney function, whereas oxidative stress demonstrates a threshold effect. These pathways may be therapeutic targets for CVD risk mitigation.

Topics: Adult; C-Reactive Protein; Dinoprost; Female; Glomerular Filtration Rate; Humans; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Male; Middle Aged; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Superoxide Dismutase