Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University of Naples, Naples, Italy.
Nephrol Dial Transplant. 2011 Sep;26(9):2891-8. doi: 10.1093/ndt/gfr186. Epub 2011 May 11.
Markers of collagen turnover have not been well studied in the context of cardiovascular disease in patients with chronic kidney disease (CKD). We investigated the associations between serum markers of collagen turnover [N-terminal procollagen type 3 propeptide (PIIINP) and carboxy-terminal telopeptide (C1TP)] and both pulse wave velocity (PWV) and left ventricular mass index (LVMI) in a CKD cohort.
The study included 242 patients (mean age 60 ± 15 years, 53% males, 80% Caucasian, CKD Stages 3-5) from the Renal Research Institute (RRI)-CKD Study. Serum PIIINP and C1TP levels were analyzed by radioimmunoassay. PWV was obtained by applanation tonometry from carotid and femoral pressure wave contours. LVMI was measured by echocardiography. Statistical analyses included Pearson's correlations and multiple linear regression.
Both PIIINP and C1TP values were significantly higher in more advanced stages of CKD (P < 0.05). A positive correlation was demonstrated between PWV and LVMI (r = 0.25, P = 0.0018), persisting after adjustment for potential confounders (partial r = 0.27, P = 0.0009). PIIINP correlated with PWV (r = 0.16, p = 0.029) and LVMI (r = 0.16, P = 0.0018), while C1TP correlated with LVMI (r = 0.18, P = 0.013) but not with PWV (r = 0.12, P = 0.09). In multivariable analysis adjusting for race, diabetes, estimated glomerular filtration rate (eGFR) and renin-angiotensin-aldosterone system inhibitors, only PWV (β = 0.45, P = 0.0017) but not LVMI (P = 0.09) remained significantly associated with serum PIIINP.
Our results demonstrate the association of PIIINP (but not C1TP), a circulating biomarker of collagen synthesis with arterial stiffness (but not with LVMI) in a CKD cohort, independent of eGFR. This suggests that altered collagen turnover may play a role in the pathogenesis of arterial stiffness in CKD.
在患有慢性肾脏病(CKD)的心血管疾病患者中,尚未很好地研究胶原蛋白转化的标志物。我们研究了 CKD 患者血清胶原蛋白转化标志物[N 端前胶原蛋白 III 型原肽(PIIINP)和羧基末端肽(C1TP)]与脉搏波速度(PWV)和左心室质量指数(LVMI)之间的相关性。
该研究纳入了来自肾脏研究所(RRI)-CKD 研究的 242 名患者(平均年龄 60 ± 15 岁,53%为男性,80%为白种人,CKD 分期 3-5 期)。通过放射免疫分析法分析血清 PIIINP 和 C1TP 水平。通过颈动脉和股动脉压力波轮廓的平板测压法获得 PWV。通过超声心动图测量 LVMI。统计分析包括 Pearson 相关性和多元线性回归。
在 CKD 更晚期,PIIINP 和 C1TP 值均显著升高(P < 0.05)。PWV 与 LVMI 呈正相关(r = 0.25,P = 0.0018),在调整潜在混杂因素后仍存在相关性(部分 r = 0.27,P = 0.0009)。PIIINP 与 PWV 相关(r = 0.16,P = 0.029)和 LVMI(r = 0.16,P = 0.0018),而 C1TP 与 LVMI 相关(r = 0.18,P = 0.013),但与 PWV 不相关(r = 0.12,P = 0.09)。在调整种族、糖尿病、估计肾小球滤过率(eGFR)和肾素-血管紧张素-醛固酮系统抑制剂的多变量分析中,只有 PWV(β = 0.45,P = 0.0017)而不是 LVMI(P = 0.09)与血清 PIIINP 显著相关。
我们的研究结果表明,在 CKD 队列中,胶原蛋白合成的循环生物标志物 PIIINP(而非 C1TP)与动脉僵硬度(而非 LVMI)相关,与 eGFR 无关。这表明胶原蛋白转化的改变可能在 CKD 中动脉僵硬度的发病机制中起作用。