Atorvastatin-induced modulation of monocyte respiratory burst in vivo in patients with IgA nephropathy: a chronic inflammatory kidney disease.
BACKGROUND
IgA nephropathy (IgAN), the most common chronic inflammatory kidney disease, implies a considerable risk of renal failure and premature cardiovascular disease. Metabolic activation of monocytes has been suggested to be an important link between chronic inflammation, oxidative stress and the development of atherosclerosis. Oxidative stress is also involved in the progression of kidney disease. In this study we investigated the degree of monocyte activation, measured by monocyte respiratory burst in patients with IgAN, since these patients represent a fairly homogenous group of patients with chronic kidney disease, and compared the results to those in healthy subjects. As anti- inflammatory effects have been ascribed to HMG-reductase inhibitors, we also examined whether treatment with atorvastatin influenced monocyte respiratory burst.


METHODS
Monocyte respiratory burst, unstimulated and stimulated by fMLP and PMA, was measured by flow cytometry in 16 patients with biopsy proven IgAN before and after 1 month of treatment with 20 mg atorvastatin/ day. Baseline values were compared to measurements in healthy subjects. Blood and urine samples, before and after statin treatment, were also analyzed for ox-LDL, inflammatory markers (CRP, MCP-1, ICAM-1, TNFR II and NGAL/MMP-9) and renal functional parameters.


RESULTS
At baseline, respiratory burst of PMA-stimulated monocytes was higher in patients with IgAN as compared to that in healthy subjects (p = 0.002). After atorvastatin treatment there was a significant reduction of unstimulated, fMLP- and PMA-stimulated monocyte respiratory burst compared to baseline values (p = 0.03, p = 0.003 and p = 0.002, respectively). For ox-LDL and inflammatory serum markers we observed no significant changes.


CONCLUSIONS
Our study demonstrates a higher monocyte respiratory burst in patients with IgAN compared to in cells from healthy controls as well as a significant reduction of this parameter after short time and low dose atorvastatin treatment.
Lundberg
S
S
Nephrology Unit, Division of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. sigrid.lundberg@karolinska.se
Lundahl
J
J
Gunnarsson
I
I
Jacobson
S H
SH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001706:Biopsy; D001711:Biotransformation; D003404:Creatinine / Q000097:blood / Q000652:urine; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006538:Heptanoic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D011758:Pyrroles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D003404:Creatinine