In the Journals

Autosomal-dominant PKD linked to oxidative stress inflammation

Autosomal dominant polycystic kidney disease appeared to be associated with the development of oxidative stress and inflammation, according to recently published data.

“Both vascular endothelial dysfunction and increased arterial stiffness are evident in patients with [autosomal dominant polycystic kidney disease (ADPKD)], even early in the course of the disease when kidney function is preserved,” Kristen L. Nowak, PhD, of the division of renal diseases and hypertension at the University of Colorado Anschutz Medical Campus, and colleagues wrote. “Oxidative stress and inflammation are also evident in patients with ADPKD, and may contribute to the development of vascular dysfunction; however, the mechanisms underlying vascular dysfunction in ADPKD are incompletely understood.”

In the cross-sectional study, researchers evaluated 61 individuals with early-stage ADPKD (eGFR ≥60 mL/min per 1.73 m²; ; mean age, 39 years) who had participated in a randomized clinical trial of spironolactone administration. Eligible participants also and a history of hypertension controlled with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Additionally, researchers included 19 healthy controls (mean age, 30 years). The researchers evaluated carotid-femoral pulse-wave velocity (arterial stiffness), and assessed vascular endothelial function via brachial artery flow-mediated dilation. Investigators also evaluated brachial artery flow-mediated dilation after an ascorbic acid infusion, to hinder vascular oxidative stress vs. saline. They gathered vascular endothelial cells from a peripheral vein to assess the expression of protein, and used ELISA or liquid chromatography-tandem mass spectrometry to evaluate circulating markers of oxidative stress, inflammation and bioactive lipid mediators.
Researchers found that the participants with ADPKD had a 15% higher carotid-femoral pulse-wave velocity vs. control participants (650 vs. 562 cm/s; P = .007), suggesting greater arterial stiffness.

The participants with ADPKD had brachial flow-mediated dilation of 8.2%, while brachial flow-mediated dilation in the controls was 10.8% vs. 4.7% (P = .08). The ascorbic acid infusion yielded a significant increase in plasma ascorbic acid concentrations in both groups, but resulted in an increase in flow-mediated dilation only in patients with ADPKD from 7.7% to 9.4% with ascorbic acid (95% CI, 0.8-2.63). Control patients showed a nonsignificant reduction in flow-mediated dilation with ascorbic acid, going from 10.8% to 10.6% (95% CI, -1.24 to 0.84; P interaction = .02). Patients with ADPKD had greater cell protein expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB; 0.48 vs. 0.41 [intensity vs. human umbilical vein endothelial cell control]; P = .03). No difference was noted based on ADPKD status in circulating markers of oxidative stress and bioactive lipid mediators.

“We have provided preliminary information supporting that oxidative stress and inflammation may be physiologic mechanisms contributing to vascular dysfunction in early-stage AKPKD,” the researchers wrote. “Our results also reiterate that arterial stiffness is significantly increased in ADPKD and develops early in the disease course before a decline in kidney function.” – by Jennifer Byrne

 

Disclosures: The researchers report no relevant disclosures.

 

 

 

Autosomal dominant polycystic kidney disease appeared to be associated with the development of oxidative stress and inflammation, according to recently published data.

“Both vascular endothelial dysfunction and increased arterial stiffness are evident in patients with [autosomal dominant polycystic kidney disease (ADPKD)], even early in the course of the disease when kidney function is preserved,” Kristen L. Nowak, PhD, of the division of renal diseases and hypertension at the University of Colorado Anschutz Medical Campus, and colleagues wrote. “Oxidative stress and inflammation are also evident in patients with ADPKD, and may contribute to the development of vascular dysfunction; however, the mechanisms underlying vascular dysfunction in ADPKD are incompletely understood.”

In the cross-sectional study, researchers evaluated 61 individuals with early-stage ADPKD (eGFR ≥60 mL/min per 1.73 m²; ; mean age, 39 years) who had participated in a randomized clinical trial of spironolactone administration. Eligible participants also and a history of hypertension controlled with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Additionally, researchers included 19 healthy controls (mean age, 30 years). The researchers evaluated carotid-femoral pulse-wave velocity (arterial stiffness), and assessed vascular endothelial function via brachial artery flow-mediated dilation. Investigators also evaluated brachial artery flow-mediated dilation after an ascorbic acid infusion, to hinder vascular oxidative stress vs. saline. They gathered vascular endothelial cells from a peripheral vein to assess the expression of protein, and used ELISA or liquid chromatography-tandem mass spectrometry to evaluate circulating markers of oxidative stress, inflammation and bioactive lipid mediators.
Researchers found that the participants with ADPKD had a 15% higher carotid-femoral pulse-wave velocity vs. control participants (650 vs. 562 cm/s; P = .007), suggesting greater arterial stiffness.

The participants with ADPKD had brachial flow-mediated dilation of 8.2%, while brachial flow-mediated dilation in the controls was 10.8% vs. 4.7% (P = .08). The ascorbic acid infusion yielded a significant increase in plasma ascorbic acid concentrations in both groups, but resulted in an increase in flow-mediated dilation only in patients with ADPKD from 7.7% to 9.4% with ascorbic acid (95% CI, 0.8-2.63). Control patients showed a nonsignificant reduction in flow-mediated dilation with ascorbic acid, going from 10.8% to 10.6% (95% CI, -1.24 to 0.84; P interaction = .02). Patients with ADPKD had greater cell protein expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB; 0.48 vs. 0.41 [intensity vs. human umbilical vein endothelial cell control]; P = .03). No difference was noted based on ADPKD status in circulating markers of oxidative stress and bioactive lipid mediators.

“We have provided preliminary information supporting that oxidative stress and inflammation may be physiologic mechanisms contributing to vascular dysfunction in early-stage AKPKD,” the researchers wrote. “Our results also reiterate that arterial stiffness is significantly increased in ADPKD and develops early in the disease course before a decline in kidney function.” – by Jennifer Byrne

 

Disclosures: The researchers report no relevant disclosures.