Effect of renin angiotensin system blockade on pentraxin 3 levels in type-2 diabetic patients with proteinuria.
OBJECTIVE
Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).


METHODS
We analyzed data of 49 persons with stage 1 diabetic CKD and 32 healthy subjects in a prospective controlled trial. Endothelial dysfunction was determined by flow-mediated dilation (FMD). Serum PTX3, high-sensitivity C-reactive protein (hs-CRP) levels, and FMD were studied in baseline and after 12 wk of ramipril therapy. Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters.


RESULTS
Serum PTX3, hsCRP, and albumin levels and proteinuria were significantly decreased, and FMD levels were significantly increased, after ramipril treatment. FMD was negatively correlated with serum PTX3, 24-h proteinuria, and hsCRP levels and positively correlated to serum albumin both at baseline and after the 12-wk treatment period. Multivariate regression analysis revealed that PTX3 levels were independently related to FMD both before and after ramipril treatment.


CONCLUSIONS
Our study shows that serum PTX3 levels are associated with endothelial dysfunction in patients with stage 1 diabetic CKD, independent of CRP. In addition, short-term ACE-inhibitor treatment significantly improves FMD and normalizes PTX3, hsCRP, and urinary protein excretion. (NCT: The study was registered in clinicaltrials.gov as NCT00674596.).
Yilmaz
Mahmut Ilker
MI
Department of Nephrology, Gulhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
Axelsson
Jonas
J
Sonmez
Alper
A
Carrero
Juan Jesus
JJ
Saglam
Mutlu
M
Eyileten
Tayfun
T
Caglar
Kayser
K
Kirkpantur
Alper
A
Celik
Turgay
T
Oguz
Yusuf
Y
Vural
Abdulgaffar
A
Yenicesu
Mujdat
M
Lindholm
Bengt
B
Stenvinkel
Peter
P
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D017257:Ramipril / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D000099153:Pentraxins
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002097:C-Reactive Protein; D017257:Ramipril; D000683:Serum Amyloid P-Component; D000099153:Pentraxins