NDT Advance Access originally published online on September 25, 2006
Nephrology Dialysis Transplantation 2006 21(12):3605-3606; doi:10.1093/ndt/gfl409
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pulse wave velocity and proteins regulating vascular calcification and bone mineralization in patients treated with peritoneal dialysis
Email: stompin{at}mp.plSir,
We read with interest the article by Dr Hermans et al. [1], concerning the relationship between non-invasive measures of aortic stiffness and fetuin-A in patients treated with maintenance dialysis [haemodialysis (HD) and peritoneal dialysis (PD)]. In our institution, we recently performed a similar study, searching for a possible association between aortic pulse wave velocity (AoPWV) and several proteins that may be involved in the regulation of pathological calcification in patients treated with PD. Fifty-five patients (25 women, 30 men) aged between 19 and 75 years (53.3 ± 12.7 years), on PD for a median period of 24 months (4–100 months) were included in this study. All patients were clinically stable over a period of at least 2 months prior to the assessment (i.e. displaying no symptoms of acute coronary event, neoplasm, infectious or non-infectious inflammatory disease, including dialysis-related peritonitis). AoPWV was measured using two pressure transducers placed on the carotid and femoral arteries and connected to an automatic processor (Complior® Colson AS, Paris, France). AoPWV was calculated from a mean of 10 consecutive pressure waveforms. The assessment of AoPWV was performed in patients with dialysis fluid completely drained out.
We measured, a broad panel of proteins which have been previously reported as factors regulating the process of pathological calcification and/or physiological bone mineralization, namely: osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), fetuin-A, matrix gla protein (MGP) and phosphatonin FGF-23. Markers of inflammation: hsCRP, tumour necrosis factor 
(TNF-) and interleukin 6 (IL-6) were also measured. All mentioned parameters were measured using ELISA, except for hsCRP (nephelometry) and OC (EIA).
In search of correlations between variables, the Pearson test for normally distributed data and the R Spearman test for those of non-parametric distribution were used. To assess the influence of tested parameters on PWV as a dependent variable, backward linear multiple regression analysis was performed.
The mean AoPWV value equaled 12.4 ± 3.89 m/s. In Table 1, the mean/median values of tested parameters, as well as their associations with AoPWV are summarized.
|
PWV has also been correlated with age (R = 0.4, P = 0.002), systolic blood pressure and pulse pressure (R = 0.29, P = 0.04 and 0.36, P = 0.007, respectively). However, when regression analysis was applied, only age remained independently associated with PWV (ß 0.422, P = 0.01; R2 for the model 0.18).
Obtained results correspond with those of Hermans et al. [1]. Although several correlations were found between PWV and tested markers, none of these were confirmed in the multivariate analysis. Fetuin-A revealed no association with aortic stiffness, even in the univariate analysis. According to the study by Hermans et al. [1], the lack of a relationship between fetuin-A and PWV might be explained by low activity of inflammation, as expressed by serum CRP. The level of inflammation in our cohort was somewhere between the results of Hermans et al. [1] and the studies cited in his paper (median CRP 4.18 g/l, mean 9.12 ± 13.9 mg/l). Alternatively, the lack of correlation between fetuin-A and aortic stiffness, in contrast to the tight association found between this marker and aortic and valvular calcification, may be explained by the fact that many other processes beyond deposition of the mineral content contribute to increased stiffness in uraemia. Higher serum fetuin-A found in PD patients as compared with HD may additionally weaken the potential relationship between serum level of this protein and vascular pathology, when analysed in PD patients only.
It is worth commenting on the association between OPG and PWV found in the univariate analysis. This decoy receptor for RANKL was initially considered as protective against excess calcification; this assumption was based on the experimental data demonstrating that mice lacking OPG gene develop extensive calcifications of the vascular system and other soft tissues [2]. However, several clinical observations revealed a positive association between OPG and vascular calcification, the advancement of coronary artery disease expressed semi-quantitatively and even mortality [3–6]. Some authors suggested that serum OPG may be the marker of low-turnover bone disease, which in turn is a well-recognized risk factor for developing vascular calcification [7–8]. Further studies are needed to clarify the role of OPG in vascular calcification and atherosclerosis, but in our opinion this factor may link these processes with bone metabolism. In summary, our study confirms the lack of an association between aortic stiffness and fetuin-A in end-stage renal disease patients, found previously by Hermans et al. [1]. The correlations between PWV and serum OC and OPG identified in univariate analysis may indicate the relationship between aortic stiffness and bone turnover. This observation appears to be the first ever in this issue performed exclusively in patients treated with PD.
This work was financially supported by scientific grant form the Jagiellonian University No. 501/NKL/80/L.
Conflict of interest statement. None declared.
nierz-Cabala2
gorzata Stompór3adysaw Suowicz1
1Chair and Department
of Nephrology
2Department of Clinical
Biochemistry
3Department of Internal Medicine
and Gerontology
Jagiellonian University
Cracow
Poland
References
- Hermans MMH, Brandenburg V, Ketteler M, et al. (2006) Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant 21:1293–1299.
[Abstract/Free Full Text] - Bucay N, Sarosi I, Dunstan CR, et al. (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268.
[Abstract/Free Full Text] - Jono S, Ikari Y, Shioi A, et al. (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194.
[Abstract/Free Full Text] - Kiechl S, Schett G, Wenning G, et al. (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109:2175–2180.
[Abstract/Free Full Text] - Nitta K, Akiba T, Uchida K, et al. (2004) Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol Dial Transplant 19:1886–1889.
[Abstract/Free Full Text] - Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC. (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024–1028.
[Abstract/Free Full Text] - Coen G, Ballanti P, Balducci A, et al. (2002) Serum osteoprotegerin and renal osteodystrophy. Nephrol Dial Transplant 17:233–238.
[Abstract/Free Full Text] - Haas M, Leko-Mohr Z, Roschger P, et al. (2002) Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients. Am J Kidney Dis 39:580–586.[ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Speer, B. Cs. Fekete, T. E. H. Othmane, T. Szabo, J. Egresits, E. Fodor, I. Kiss, A. G. Logan, J. Nemcsik, A. Szabo, et al. Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients Nephrol. Dial. Transplant., May 13, 2008; (2008) gfn242v2. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||