Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Menon
Vandana
V
Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA. Vandana.menon@gmail.com
Rudym
Darya
D
Chandra
Priya
P
Miskulin
Dana
D
Perrone
Ronald
R
Sarnak
Mark
M
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood / Q000150:complications* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D015850:Interleukin-6; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D015237:Dinoprost; D013482:Superoxide Dismutase