Vascular calcification is strongly associated with cardiovascular disease and mortality. However, some factors related to vascular calcification in patients with end-stage renal disease receiving peritoneal dialysis (PD) remain unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23), magnesium, and phosphate clearance with vascular calcification in PD subjects, assessed by plain radiographs.
Methods
Simple vascular calcification scores (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for ≥ 6 months (43 women, median age 39 years, median time on PD 1.4 years). Levels of OPG, OPN, OCN, and FGF-23 were determined by luminometry.
Results
Serum OPG levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3; n = 19 with KI > 7) compared with those with less calcification (p < 0.001). Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had significantly lower renal phosphate clearance. Multiple regression analysis showed that vascular calcification assessed by SVCS was associated with age (r = 0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r = 0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and magnesium were not associated with vascular calcification.
Conclusions
Higher levels of OPG were consistently associated with vascular calcification in subjects on PD.
KredietR.T., BalafaO.Cardiovascular risk in the peritoneal dialysis patient.Nat Rev Nephrol2010; 6: 451–60.
2.
WangA.Y.Vascular and other tissue calcification in peritoneal dialysis patients.Perit Dial Int2009; 29(Suppl 2): S9–14.
3.
WangY.Vascular and valvular calcification in chronic peritoneal dialysis patients.Int J Nephrol2011; 2011: 198045.
4.
LevyR., Gal-MoscoviciA.Renal osteodystrophy in peritoneal dialysis: special considerations.Perit Dial Int2008; 28(Suppl 2): S12–9.
5.
RrojiM., SeferiS., CafkaM., PetrelaE., LikajE., BarbullushiM.Is residual renal function and better phosphate control in peritoneal dialysis an answer for the lower prevalence of valve calcification compared to hemodialysis patients?Int Urol Nephrol2014; 46: 175–82.
6.
StompórT., PasowiczM., SulłowiczW., Dembińska-KiecA., JandaK., WójcikK.An association between coronary artery calcification score, lipid profile, and selected markers of chronic inflammation in ESRD patients treated with peritoneal dialysis.Am J Kidney Dis2003; 41: 203–11.
7.
AmmiratiA.L., DalboniM.A., CendorogloM., DraibeS.A., SantosR.D., MinameM.The progression and impact of vascular calcification in peritoneal dialysis patients.Perit Dial Int2007; 27: 340–6.
8.
LeeH., HwangY.H., JungJ.Y., NaK.Y., KimH.S., SonM.J.Comparison of vascular calcification scoring systems using plain radiographs to predict vascular stiffness in peritoneal dialysis patients.Nephrology (Carlton)2011; 16: 656–62.
9.
StómporT.An overview of the pathophysiology of vascular calcification in chronic kidney disease.Perit Dial Int2007; 27(Suppl 2): S215–22.
10.
QuercioliA., MontecuccoF., BertolottoM., OttonelloL., PendeA., MachF.Coronary artery calcification and cardiovascular risk: the role of RANKL/OPG signalling.Eur J Clin Invest2010; 40: 645–54.
11.
WangK.X., DenhardtD.T.Osteopontin: role in immune regulation and stress responses.Cytokine Growth Factor Rev2008; 19: 333–45.
12.
RennenbergR.J., de LeeuwP.W., KesselsA.G., SchurgersL.J., VermeerC., van EngelshovenJ.M.Calcium scores and matrix Gla protein levels: association with vitamin K status.Eur J Clin Invest2010; 40: 344–9.
13.
LarssonT.E.FGF23 beyond mineral metabolism: a bridge to cardiovascular disease.Clin J Am Soc Nephrol2011; 6: 2735–7.
14.
WeiM., EsbaeiK., BargmanJ., OreopoulosD.G.Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review.Perit Dial Int2006; 26: 366–73.
15.
YavuzA., ErsoyF.F., PassadakisP.S., TamP., EvaggelosD.M., KatopodisK.P.Phosphorus control in peritoneal dialysis patients.Kidney Int Suppl2008; 108: S152–8.
16.
SchmittC.P., BorzychD., NauB., WühlE., ZurowskaA., SchaeferF.Dialytic phosphate removal: a modifiable measure of dialysis efficacy in automated peritoneal dialysis.Perit Dial Int2009; 29(4): 465–71.
KauppilaL.I., PolakJ.F., CupplesL.A., HannanM.T., KielD.P., WilsonP.W.New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.Atherosclerosis1997; 132: 245–50.
19.
AdragãoT., PiresA., BirneR., CurtoJ.D., LucasC., GonçalvesM.A plain X-ray vascular calcification score is associated with arterial stiffness and mortality in dialysis patients.Nephrol Dial Transplant2009; 24: 997–1002.
20.
BellasiA., FerramoscaE., MuntnerP., RattiC., WildmanR.P., BlockG.A.Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients.Kidney Int2006; 70: 1623–8.
21.
NolphK.D., MooreH.L., TwardowskiZ.J., KhannaR., ProwantB., MeyerM.Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis.ASAIO J1992; 38: M139–42.
22.
TwardowskiZ.J., NolphK.D., KhannaR., GluckZ., ProwantB.F., RyanL.P.Daily clearances with continuous ambulatory peritoneal dialysis and nightly peritoneal dialysis.ASAIO Trans1986; 32: 575–80.
23.
LachinJ.M.Introduction to sample size determination and power analysis for clinical trials.Control Clin Trials1981; 2: 93–113.
24.
NakamuraM., UdagawaN., MatsuuraS., MogiM., NakamuraH., HoriuchiH.Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.Endocrinology2003; 144: 5441–9.
25.
HuangJ.W., LienY.C., YangC.Y., LiuK.L., WuC.F., YenC.J.Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis.Nutr Metab Cardiovasc Dis2014; 24: 236–42.
26.
MinH., MoronyS., SarosiI., DunstanC.R., CapparelliC., ScullyS.Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis.J Exp Med2000; 192(4): 463–74.
27.
Van CampenhoutA., GolledgeJ.Osteoprotegerin, vascular calcification and atherosclerosis.Atherosclerosis2009; 204: 321–9.
28.
Collin-OsdobyP.Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.Circ Res2004; 95: 1046–57.
29.
Collin-OsdobyP., RotheL., AndersonF., NelsonM., MaloneyW., OsdobyP.Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis.J Biol Chem2001; 276: 20659–72.
30.
MontagnanaM., LippiG., DaneseE., GuidiG.C.The role of osteoprotegerin in cardiovascular disease.Ann Med2013; 45: 254–64.
31.
KooH.M., DoH.M., KimE.J., LeeM.J., ShinD.H., KimS.J.Elevated osteoprotegerin is associated with inflammation, malnutrition and new onset cardiovascular events in peritoneal dialysis patients.Atherosclerosis2011; 219: 925–30.
32.
Avila-DíazM., Mora-VillalpandoC., Prado-Uribe MdelC., Orihuela-RodriguezO., Villegas-AnteloE., Gómez-NoriegaA.M.De novo development of heart valve calcification in incident peritoneal dialysis patients.Arch Med Res2013; 44: 638–44.
33.
HuangJ.W., LienY.C., YangC.Y., LiuK.L., WuC.F., YenC.J.Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis.Nutr Metab Cardiovasc Dis2014; 24: 236–42.
34.
KrzanowskiM., JandaK., DumnickaP., DubielM., StompórM., Kusnierz-CabalaB.Relationship between aortic pulse wave velocity, selected proinflammatory cytokines, and vascular calcification parameters in peritoneal dialysis patients.J Hypertens2014; 32: 142–8.
35.
SmithE.R., FordM.L., TomlinsonL.A., BodenhamE., McMahonL.P., FareseS.Serum calcification propensity predicts all-cause mortality in predialysis CKD.J Am Soc Nephrol2014; 25: 339–48.
36.
InabaM., OkunoS., ImanishiY., YamadaS., ShioiA., YamakawaT.Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients.Osteoporos Int2006; 17: 1506–13.
37.
KendrickJ., ChoncholM.The role of phosphorus in the development and progression of vascular calcification.Am J Kidney Dis2011; 58: 826–34.
38.
WangA.Y., WooJ., SeaM.M., LawM.C., LuiS.F., LiP.K.Hyperphosphatemia in Chinese peritoneal dialysis patients with and without residual kidney function: what are the implications?Am J Kidney Dis2004; 43: 712–20.
39.
Kuro-oM.Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism.Nat Rev Nephrol2013; 9: 650–60.
40.
GutiérrezO.M., MannstadtM., IsakovaT., Rauh-HainJ.A., TamezH., ShahA.Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.N Engl J Med2008; 359: 584–92.
41.
KimH.J., ParkM., ParkH.C., JeongJ.C., KimD.K., JooK.W.Baseline FGF23 is associated with cardiovascular outcome in incident PD patients.Perit Dial Int2014. In press.
42.
JeanG., BressonE., TerratJ.C., VanelT., HurotJ.M., LorriauxC.Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences.Nephrol Dial Transplant2009; 24: 948–55.
43.
CraverL., DussoA., Martinez-AlonsoM., SarroF., ValdivielsoJ.M., FernándezE.A low fractional excretion of phosphate/FGF23 ratio is associated with severe abdominal aortic calcification in stage 3 and 4 kidney disease patients.BMC Nephrol2013; 14: 221.
44.
DominguezJ.R., ShlipakM.G., WhooleyM.A., IxJ.H.Fractional excretion of phosphorus modifies the association between fibroblast growth factor-23 and outcomes.J Am Soc Nephrol2013; 24: 647–54.
45.
ShahN., BernardiniJ., PirainoB.Prevalence and correction of 25(OH) vitamin D deficiency in peritoneal dialysis patients.Perit Dial Int2005; 25(4): 362–6.
46.
EllamT.Confounded complexity: vitamin D, parathyroid hormone, and metabolic syndrome in peritoneal dialysis.Perit Dial Int2014; 34(4): 333–7.
47.
ZittermanA., SchleithoffS.S., KoerferR.Vitamin D and vascular calcification.Curr Opin Lipidol2007; 18: 41–6.
48.
SchlieperG.Vascular calcification in chronic kidney disease: not all arteries are created equal.Kidney Int2014; 85(3): 501–3.
