Serum Levels of Calcification Inhibition Proteins and Coronary Artery Calcium Score: Comparison between Transplantation and Dialysis

Abstract

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 ± 12 years; 30 males, 21 females; previous D duration 4.8 ± 4.2 years; Tx since 6.6 ± 5.5 years; Cr 1.8 ± 0.6 mg/dl) and in 49 D patients (age 49 ± 14 years; 30 males,19 females; D duration 5.6 ± 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 ± 1,637 vs. 1,311 ± 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: r_s = 0.439, p < 0.001, and r_s = 0.510, p < 0.0001; D: r_s = 0.471, p < 0.001, and r_s = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (r_s = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (r_s = –0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (r_m = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (r_m = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.

Risk Factors Associated with Coronary Artery Calcification Should Be Examined before Kidney Transplantation

“…As in most other studies examining dialysis (Kraśniak et al 2007) or Tx patients (Rosas et al 2005;Mazzaferro et al 2007;Seyahi et al 2011) CAC significantly correlated with age in both examined groups. In addition, patients from both subgroups with CAC had undergone significantly longer CKD and/or dialysis duration than patients without CAC.…”

“…By searching Medline and PubMed databases, Hamirani et al (2008) found variable association between CAC and inflammation in the general population. Nevertheless, in Tx patients (Mazzaferro et al 2007) and dialysis patients (Kraśniak et al 2007;Coen et al 2006), this relationship was closer in cross-sectional studies and in CAC progression investigations (Mazzaferro et al 2009;Coen et al 2010).…”

“…Moe et al (2004) and Mazzafero et al (2007) compared mean CAC score, potential promoters and inhibitors for CAC and outcome in Tx recipients with values for dialysis patients. The Tx patients had CAC scores of lower severity, no net change in CAC with time (Moe et al 2004), less inflammation (Mazzaferro et al 2007), higher levels of calcification inhibitors (Mazzaferro et al 2007) and a better survival rate than dialysis patients (Moe et al 2004). However, we evaluated Tx recipients with age and gender matched stage 2-5 CKD patients not requiring dialysis.…”

“…Currently accepted opinions propose that in the uremic milieu, vascular calcifications may result from both an imbalance in divalent ions and a deficit of inhibitory proteins, eventually leading to phenotypic change and calcium deposition (Ketteler et al 2005). It could be expected that, after successful kidney transplantation and definite improvement of the uremic milieu, the imbalance between promoters and inhibitors of vascular calcification would be lessened (Mazzaferro et al 2007). However, the prevalence of renal transplant patients with CAC still remains very high.…”

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

“…Restricting the analysis to patients with a baseline score > 0 (n = 161) did not change the results (data not shown). Older age and male gender are classical CV risk factors (23,24,18,40). Like for CAC progression, use of statin and baseline score were associated with AoC progression.…”