Abstract 4842: Is Altered Collagen Turnover Related to the Development of Stiff Arteries and Hearts in Chronic Kidney Disease?

Abstract

Introduction Cardiovascular mortality is increased in chronic kidney disease (CKD) in a graded inverse relationship with glomerular filtration rate (GFR). We and others have demonstrated increased arterial stiffness which also has a graded relationship with GFR and is of prognostic significance. Experimental studies have shown increased collagen associated proteins in the intimal and medial arterial layers which appear to precede vascular calcification in CKD. We hypothesised that active, collagen dependent, fibrotic processes might increase arterial stiffness and compromise ventricular relaxation thereby contributing to the high levels of cardiovascular disease. Methods We studied 117 patients with early stage CKD (mean eGFR 51 ml/min/1.73m 2, range 30 – 89), controlled hypertension (<130/85mmHg) no history of cardiovascular disease or diabetes. Arterial stiffness was assessed using pulse wave velocity (PWV) by applanation tonometry and aortic distensibility in the ascending aorta by CMR (1.5T). Early myocardial relaxation velocities (Em) and E/Em ratio (marker of LVEDP) were measured by echocardiography. Serological collagen turnover markers; amino-terminal propeptide of procollagen type III (PNIIIP a measure of collagen synthesis) and C-terminal telopeptide of type I collagen (CTx a measure of collagen degradation), were measured by radioimmunoassay and ECLIA immunoassay. Results PNIIIP was inversely correlated with eGFR ( r = 0.52 p<0.01), aortic distensibilty ( r = 0.23 p<0.05) and Em ( r = 0.24 p<0.05) and positively correlated with PWV ( r = 0.23 p<0.05), and E/Em ( r = 0.2 p<0.05). CTx was inversely correlated with eGFR ( r = 0.31 p<0.01) but was not correlated with markers of arterial or ventricular stiffness Conclusion Collagen synthesis, arterial and ventricular stiffness are all increased with deteriorating renal function even from the earliest stages of CKD. This suggests that collagen metabolism plays an important role in the development of arterial and myocardial stiffness in CKD. Collagen turnover is a possible new therapeutic target in the prevention of cardiovascular disease in CKD.