HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by García–López, E. Articles by Stenvinkel, P. Search for Related Content PubMed Articles by García–López, E. Articles by Stenvinkel, P.

RISK FACTORS FOR CARDIOVASCULAR DISEASE IN PATIENTS UNDERGOING PERITONEAL DIALYSIS

Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

Correspondence to: P. Stenvinkel, Department of Renal Medicine, K56, Karolinska University Hospital at Huddinge, Stockholm 14186 Sweden. peter.stenvinkel{at}ki.se

	ABSTRACT

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 

Patients on peritoneal dialysis (PD) are at high cardiovascular risk. Although some risk factors are unmodifiable (for example, age, sex, genetics), others are exacerbated in the unfriendly uremic milieu (inflammation, oxidative stress, mineral disturbances) or contribute per se to kidney disease and cardiovascular progression (diabetes mellitus, hypertension). Moreover, several factors associated with PD therapy may both increase (by altered lipid profile, hyperinsulinemia, and formation of advanced glycation end-products) and decrease (by better blood pressure control and anemia management) cardiovascular risk. The present review discusses recent findings and therapy trends in cardiovascular research on the PD population, with emphasis on the roles of inflammation, insulin resistance, homocysteinemia, dyslipidemia, vascular calcification, and genetics/epigenetics.

KEY WORDS: Cardiovascular disease; inflammation; vascular calcification; homocysteine.

Patients with chronic kidney disease (CKD) suffer from substantially increased rates of cardiovascular (CV) morbidity and mortality, attributable to a higher prevalence of both classical and nontraditional risk factors (1). Moreover, uremia itself contributes to cardiac pathology: many studies show that CKD is an independent risk factor for CV morbidity and mortality even after adjustment for traditional and nontraditional risk factors (2).

Cardiovascular disease (CVD) is the main cause of death in patients requiring renal replacement therapy. Sudden cardiac death, coronary artery disease, stroke, and peripheral vascular disease are common, and cardiac arrest and arrhythmia are the most common causes of CV death in this population. Despite major technologic improvements in dialysis therapies and small-solute clearances, CKD patients show a CVD death rate that is 5–25 times higher than that seen in the general population (3). Recent prospective studies such as HEMO (4) and ADEMEX (5) have shown that further increasing the dialysis dose does not lower mortality. Thus, it is evident that, to improve the poor survival of end-stage renal disease (ESRD) patients, nephrologists must identify the factors that best explain the marked discrepancy between vascular and chronologic age in this patient group (3).

Although non-atherosclerotic CVD such as volume overload and left ventricular hypertrophy may be the most important contributors to the high CV mortality rate in ESRD patients, recent evidence suggests that ESRD patients are indeed subject to an accelerated atherosclerotic process. Aortic stiffening and arterial wall thickening are prominent findings long before the start of renal replacement therapy, and studies performed on partially nephrectomized mice deficient in apolipoprotein E demonstrated that the uremic milieu per se accelerates atherosclerosis (4).

The interplay of many pathways (Figure 1) may be behind the accelerated atherosclerosis seen in peritoneal dialysis (PD) patients (5). Although certain traditional (that is, Framingham) risk factors such as age (6) and sex (7) are not modifiable, optimal management of underlying comorbid conditions could reduce the burden of CVD.

View larger version (2K): [in this window] [in a new window]   Figure 1 — Traditional, novel, and uremia-specific risk factors that contribute to the burden of cardiovascular disease in patients undergoing peritoneal dialysis.

Diabetes mellitus, associated with a 65% increase in the risk of CVD as compared with the risk in nondiabetic CKD patients (8), contributes to CVD in a complex manner that involves dyslipidemia and deposition of advanced glycation end-products (among other factors), and that is further worsened by hypertension. Hypertension, a key risk factor for the development of stroke and left ventricular dysfunction, is highly prevalent (75%–85%) in the dialysis population and further contributes to the high risk for vascular disease in CKD patients. Novel risk factors, such as endothelial dysfunction (as characterized by impaired nitric oxide synthesis, altered smooth muscle cell proliferation, reduced angiogenesis, activation of coagulation, and increased cell adhesion to the vascular wall), may move to the front line. Furthermore, the accumulation of uremic toxins such as proinflammatory cytokines, asymmetric dimethylarginine, homocysteine, and advanced glycation end-products is particularly related to vascular inflammation and oxidative stress induction.

Because reports from various U.S. dialysis registries are inconsistent regarding the effect of hemodialysis (HD) and PD on outcome, it is not yet known whether patients treated by PD are more or less prone to develop vascular complications.

	DYSLIPIDEMIA

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Dyslipidemia seems to exhibit a more atherogenic profile in patients treated with PD than in those treated with HD, with PD patients having higher levels of total and low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides, and lower levels of high-density lipoprotein cholesterol (9). Although the causes of this constellation are not fully understood, intraperitoneal glucose loading and protein loss across the peritoneum are both likely to contribute. Levels of lipoprotein(a) are also markedly elevated in PD patients, and although the significance of this alteration in PD is still uncertain, recent data from the Diamant Study indicate that lipoprotein(a) is independently associated with CV morbidity and mortality in a combined group of HD and PD patients (6).

Because statins reduce the incidence of CV events both in the general population and in patients with type 2 diabetes, this class of drugs has been traditionally considered safe and efficient for treating dyslipidemia in PD (10). However, the benefit of statins in patients receiving HD has been questioned by the Die Deutsche Diabetes Dialyse study (11), where atorvastatin had (surprisingly) no effect on CV death, nonfatal myocardial infarction, and stroke. To the best of our knowledge, no ongoing prospective studies are examining the long-term effects of statins on CV outcome in PD patients.

	INSULIN RESISTANCE

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Current data suggest that insulin resistance (IR) is prevalent in CKD patients and may be present in the early stages of CKD (8). The potential for IR to promote vascular damage, regardless of whether it coexists with other vascular risk factors, is well documented (12). Few reports analyze the role of IR in the PD population, but the associations recently noted between IR and impaired cardiac fatty-acid metabolism, which may contribute to left ventricular dysfunction in HD patients, are interesting (13). Evidence in the literature is increasingly showing that angiotensin converting-enzyme inhibitors and thiazolidinediones can be used to modulate IR (12).

Glucose loading in PD patients has been postulated to possibly worsen insulin sensitivity. However, those reports are controversial: although patients on continuous cycling PD (as compared with those on HD) showed increased IR and insulin sensitivity (14), chronic ambulatory PD therapy normalized IR in a manner similar to that seen with HD therapy (15). The use of icodextrin dialysate for the long dwell could be a promising solution to this problem, and dialysate of this kind has been reported to reduce serum insulin levels and to increase insulin sensitivity (16).

	INFLAMMATION

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Inflammation has been proposed to be a fundamental promoter of atherosclerosis, interacting with many pathophysiologic pathways to lead to vascular damage. One of these mechanisms could imply stimulation of fibrinogen synthesis by interleukin-6 (IL-6) via a specific IL-6–sensitive sequence in the fibrinogen gene (17).

Several studies have demonstrated a dose–response relationship between C-reactive protein (CRP) and mortality in CKD (18). Of these, some dealt with PD patients specifically, showing that elevated CRP is an independent predictor of nonfatal myocardial infarction (19) and of increased CVD incidence (20), with PD patients in the top CRP quartile having a CV risk 5 times that of patients in the lower quartile (20). These hypotheses have gained in strength, given that a recent study showed that inflammatory markers were associated with increasing carotid intima media thickness during 1 year of PD (21).

Patients with ESRD often exhibit an activated inflammatory response (22), but whether PD (as compared with HD) is associated with more or less inflammation is unknown. Although a suggestion has been made that less induction of inflammatory activity occurs during PD (23), other authors reported that PD is associated with increased arterial stiffness and endothelial dysfunction (24).

Carrero et al. (25) recently observed that, during the first year of dialysis, CRP concentrations decreased significantly in HD patients, but not in PD patients. The reason for this latter finding is unclear, but frequent heparinization might be speculated to hamper the proinflammatory state in HD patients (25). Various factors associated with the PD procedure per se, such as peritonitis, percutaneous PD catheter infection, fluid overload, exposure to endotoxins present in dialysate, or use of bioincompatible PD solutions (26) may also promote inflammation. Furthermore, increased levels of tumor necrosis factor and of interleukin-1, generated in response to stimuli such as low tissue perfusion or hypoxia, have been proposed to possibly play important roles in cardiac cachexia and prognosis (27). In this sense, diuretic treatment to control volume status in patients with congestive heart failure was associated with a significant decrease in systemic endotoxin levels (28). Consistent with that finding, a higher proportion of patients with inflammation showed reduced total fluid removal (29).

Available evidence suggests that preservation of residual renal function (RRF) in PD patients could be of utmost importance in their management (30). Indeed, in PD patients, RRF is intimately associated with inflammation (31) and endothelial dysfunction (32), independent of CV status. This hypothesis merits further consideration, because the combination of loss of RRF with inflammation and cardiac hypertrophy showed an additive effect, enhancing the risk of mortality and CV death in PD patients (33).

	HOMOCYSTEINE

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Plasma total homocysteine is moderately elevated in the initial phases of CKD, and it increases as the glomerular filtration rate deteriorates. Homocysteine is increased in almost all ESRD patients, and it is an independent and important contributor to CV death in PD patients (6).

Prospective observational studies evaluating the relationship between homocysteine and mortality or CV events report both positive and negative associations (34). These opposing associations are in apparent contrast with experimental findings showing that this sulfur amino acid is vasculotoxic. However, because homocysteine circulates bound to albumin, negative associations most likely reflect the deleterious effects of inflammation and wasting (35,36). In fact, in HD patients without signs of wasting and inflammation, elevated levels of homocysteine were strong predictors for all-cause and CV mortality (20).

High intakes of folic acid and vitamins B₆ and B₁₂ in PD patients can normalize homocysteine levels (37), but no randomized trials with hard outcomes have yet been reported in this population. And because specific mutations in the MTHFR gene have been associated with CV death in hyperhomocysteinemic dialysis patients (6), genetic analyses might be of importance in defining optimal CV therapeutic prevention.

	VASCULAR CALCIFICATION

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Recent evidence suggests that vascular calcification, which affects arterial media, atherosclerotic plaques, the myocardium, and the heart valves, is a common feature of ESRD (38). The prevalence and extent of vascular calcifications are strongly predictive of CVD and mortality in dialysis patients (39). Moreover, Wang et al. (40) demonstrated that cardiac valve calcifications are more frequent in PD patients with inflammation than in those without and entail a 6-times-heightened risk of CV death.

Increased calcification in PD patients has been associated with increased inflammation (21), low levels of fetuin-A (40), and the use of calcium-based phosphate binders (41). However, novel therapies show promising results, with sevelamer preventing uremia-enhanced progression of atherosclerosis through effects on mineral metabolism, inflammation, and oxidative stress in mice deficient in apolipoprotein E (42).

	GENETIC AND EPIGENETIC FACTORS

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Genetic factors may affect the prevalence of adverse symptoms in ESRD, which in turn may affect the risk of vascular complications and outcome in the PD population.

For instance, a single nucleotide polymorphism in the IL-6 gene has been associated with higher plasma IL-6 levels and comorbidity score in HD patients (35) and with higher diastolic blood pressure and left ventricular mass (36). Moreover, the angiotensin converting-enzyme polymorphism may determine recombinant human erythropoietin responsiveness in PD patients (43), constituting a prescreening tool for relative erythropoietin resistance.

Some polymorphisms at the human vitamin D receptor are associated with increased risk of developing hypercalcemia (44), and the modulation of NO activity via the endothelial nitric oxide synthase polymorphism (45) and a functionally relevant polymorphism of IL-6 (46), may have a considerable effect on basal peritoneal permeability.

In the future these novel tools can provide the nephrology community with a more precise approach to identifying high-risk PD patients and developing accurate personalized treatment strategies.

A novel approach in atherosclerosis research focuses on the role of epigenetics, which studies changes in gene expression that are not coded into the DNA sequence itself, but that produce post-translational modifications in DNA proteins. These epigenetic modifications may endure in several subsequent cell generations.

For instance, changes in genomic DNA methylation have important regulatory functions in normal and pathologic cellular processes, but they are also crucial in conditions such as aging, cancer, mental health, and arteriosclerosis (47). Persistent inflammation seems to be associated with DNA hypermethylation (48), and so further studies are needed to determine if aberrant DNA alterations contribute to accelerated atherosclerosis in uremia. Because epigenetic DNA modifications are potentially reversible, the possibility of developing epigenetic therapies exists.

	CONCLUSIONS

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 
Risk factors for CVD are highly prevalent in PD patients, and PD as such—and in particular episodes of infection and the peritoneal glucose load—may possibly contribute to further increases in the risk for CVD. On the other hand, as compared with HD, PD has some potential CV advantages—in particular, avoidance of the unphysiologic fluctuations in fluid and solute status associated with intermittent dialysis. However, whether the risk for CVD differs between the two dialysis modalities is not currently known.

	ACKNOWLEDGMENTS

 
Juan Jesus Carrero is supported by a fellowship from the European Renal Association/European Dialysis and Transplant Association.

	REFERENCES

TOP ABSTRACT DYSLIPIDEMIA INSULIN RESISTANCE INFLAMMATION HOMOCYSTEINE VASCULAR CALCIFICATION GENETIC AND EPIGENETIC FACTORS CONCLUSIONS REFERENCES

 

1. Foley RN. Clinical epidemiology of cardiac disease in dialysis patients: left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial 2003;16 : 111-17.[Medline]
2. Vanholder R, Massy Z, Argiles A, Spasovski G, Verbeke F, Lameire N. Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant 2005;20 : 1048-56.[Abstract/Free Full Text]
3. Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol1998; 9(Suppl 12):S16 -23.[Medline]
4. Massy ZA, Ivanovski O, Nguyen–Khoa T, Angulo J, Szumilak D, Mothu N, et al. Uremia accelerates both atherosclerosis and arterial calcification in apolipoprotein E knock-out mice. J Am Soc Nephrol 2005; 16:109 -16.[Abstract/Free Full Text]
5. Pecoits–Filho R. The peritoneal cavity: a room with a view to the endothelium. Perit Dial Int 2005;25 : 432-4.[Free Full Text]
6. Pernod G, Bosson JL, Golshayan D, Barro C, Forneris G, Martina G, et al. Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort. Kidney Int2006; 69:1424 -30.[Medline]
7. Jungers P, Massy ZA, Nguyen Khoa T, Fumeron C, Labrunie M, Lacour B, et al. Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study. Nephrol Dial Transplant1997; 12:2597 -602.[Abstract/Free Full Text]
8. Alvestrand A. Carbohydrate and insulin metabolism in renal failure. Kidney Int Suppl 1997;62 : S48-52.[Medline]
9. Prichard SS. Impact of dyslipidemia in end-stage renal disease. J Am Soc Nephrol 2003;14 (Suppl 4):S315 -20.[Abstract/Free Full Text]
10. Saltissi D, Morgan C, Rigby RJ, Westhuyzen J. Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing chronic renal dialysis. Am J Kidney Dis 2002;39 : 283-90.[Medline]
11. Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353 : 238-48.[Abstract/Free Full Text]
12. Shen Y, Peake PW, Kelly JJ. Should we quantify insulin resistance in patients with renal disease? Nephrology (Carlton)2005; 10:599 -605.[Medline]
13. Nishimura M, Murase M, Hashimoto T, Kobayashi H, Yamazaki S, Imai R, et al. Insulin resistance and impaired myocardial fatty acid metabolism in dialysis patients with normal coronary arteries. Kidney Int 2006;69 : 553-9.[Medline]
14. Mak RH. Insulin resistance in uremia: effect of dialysis modality. Pediatr Res 1996;40 : 304-8.[Medline]
15. Kobayashi S, Maejima S, Ikeda T, Nagase M. Impact of dialysis therapy on insulin resistance in end-stage renal disease: comparison of haemodialysis and continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 2000;15 : 65-70.[Abstract/Free Full Text]
16. Amici G, Orrasch M, Da Rin G, Bocci C. Hyperinsulinism reduction associated with icodextrin treatment in continuous ambulatory peritoneal dialysis patients. Adv Perit Dial 2001;17 : 80-3.[Medline]
17. Kaysen GA, Don BR. Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease. Kidney Int 2003;63 (Suppl 84):S94 -7.
18. Pecoits–Filho R, Stenvinkel P, Wang AY, Heimbürger O, Lindholm B. Chronic inflammation in peritoneal dialysis: the search for the holy grail? Perit Dial Int 2004;24 : 327-39.[Abstract/Free Full Text]
19. Herzig KA, Purdie DM, Chang W, Brown AM, Hawley CM, Campbell SB, et al. Is C-reactive protein a useful predictor of outcome in peritoneal dialysis patients? J Am Soc Nephrol2001; 12:814 -21.[Abstract/Free Full Text]
20. Ducloux D, Klein A, Kazory A, Devillard N, Chalopin JM. Impact of malnutrition–inflammation on the association between homocysteine and mortality. Kidney Int 2006;69 : 331-5.[Medline]
21. Stompor T, Krasniak A, Sulowicz W, Dembinska–Kiec A, Janda K, Wojcik K, et al. Changes in common carotid artery intima-media thickness over 1 year in patients on peritoneal dialysis. Nephrol Dial Transplant 2005; 20:404 -12.[Abstract/Free Full Text]
22. Fine A. Relevance of C-reactive protein levels in peritoneal dialysis patients. Kidney Int 2002;61 : 615-20.[Medline]
23. Haubitz M, Brunkhorst R, Wrenger E, Froese P, Schulze M, Koch KM. Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal dialysis therapy. Perit Dial Int 1996;16 : 158-62.[Abstract/Free Full Text]
24. Covic A, Goldsmith DJ, Florea L, Gusbeth–Tatomir P, Covic M. The influence of dialytic modality on arterial stiffness, pulse wave reflections, and vasomotor function. Perit Dial Int2004; 24:365 -72.[Abstract/Free Full Text]
25. Carrero JJ, Axelsson J, Avesani CM, Heimbürger O, Lindholm B, Stenvinkel P. Being an inflamed peritoneal dialysis patient—a Dante's journey. Contrib Nephrol 2006;150 : 144-51.[Medline]
26. Zemel D, Krediet RT. Cytokine patterns in the effluent of continuous ambulatory peritoneal dialysis: relationship to peritoneal permeability. Blood Purif 1996;14 : 198-216.[Medline]
27. Freeman LM, Roubenoff R. The nutrition implications of cardiac cachexia. Nutr Rev 1994;52 : 340-7.[Medline]
28. Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999;353 : 1838-42.[Medline]
29. Chung SH, Heimbürger O, Stenvinkel P, Wang T, Lindholm B. Influence of peritoneal transport rate, inflammation, and fluid removal on nutritional status and clinical outcome in prevalent peritoneal dialysis patients. Perit Dial Int 2003;23 : 174-83.[Abstract/Free Full Text]
30. Wang AY, Lai KN. The importance of residual renal function in dialysis patients. Kidney Int 2006;69 : 1726-32.[Medline]
31. Wang AY, Wang M, Woo J, Lam CW, Lui SF, Li PK, et al. Inflammation, residual kidney function, and cardiac hypertrophy are interrelated and combine adversely to enhance mortality and cardiovascular death risk of peritoneal dialysis patients. J Am Soc Nephrol 2004; 15:2186 -94.[Abstract/Free Full Text]
32. Wang AY, Lam CW, Wang M, Woo J, Chan IH, Lui SF, et al. Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients. Am J Kidney Dis 2005;45 : 715-29.[Medline]
33. Chung SH, Heimbürger O, Stenvinkel P, Bergström J, Lindholm B. Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis. Nephrol Dial Transplant 2001;16 : 2240-5.[Abstract/Free Full Text]
34. Suliman ME, Bárány P, Kalantar–Zadeh K, Lindholm B, Stenvinkel P. Homocysteine in uraemia—a puzzling and conflicting story. Nephrol Dial Transplant2005; 20:16 -21.[Free Full Text]
35. Balakrishnan VS, Guo D, Rao M, Jaberm BL, Tighiouart H, Freeman RL, et al. Cytokine gene polymorphisms in hemodialysis patients: association with comorbidity, functionality, and serum albumin. Kidney Int 2004;65 : 1449-60.[Medline]
36. Losito A, Kalidas K, Santoni S, Jeffery S. Association of interleukin-6-174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int 2003; 64:616 -22.[Medline]
37. Righetti M, Tommasi A, Lagona C, La Rosa L, Uccellini M, Sessa A. Effective homocysteine-lowering vitamin B treatment in peritoneal dialysis patients. Perit Dial Int 2004;24 : 373-7.[Abstract/Free Full Text]
38. Wei M, Esbaei K, Bargman J, Oreopoulos DG. Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review. Perit Dial Int2006; 26:366 -73.[Abstract/Free Full Text]
39. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001;38 : 938-42.[Abstract/Free Full Text]
40. Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant2005; 20:1676 -85.[Abstract/Free Full Text]
41. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62 : 245-52.[Medline]
42. Phan O, Ivanovski O, Nguyen–Khoa T, Mothu N, Angulo J, Westenfeld R, et al. Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E–deficient mice. Circulation 2005;112 : 2875-82.[Abstract/Free Full Text]
43. Sharples EJ, Varagunam M, Sinnott PJ, McCloskey DJ, Raftery MJ, Yaqoob MM. The effect of proinflammatory cytokine gene and angiotensin-converting enzyme polymorphisms on erythropoietin requirements in patients on continuous ambulatory peritoneal dialysis. Perit Dial Int 2006; 26:64 -8.[Abstract/Free Full Text]
44. Akcay A, Ozdemir FN, Sezer S, Micozkadioglu H, Arat Z, Atac FB, et al. Association of vitamin D receptor gene polymorphisms with hypercalcemia in peritoneal dialysis patients. Perit Dial Int 2005; 25(Suppl 3):S52 -5.[Abstract/Free Full Text]
45. Akcay A, Micozkadioglu H, Atac FB, Agca E, Ozdemir FN. Relationship of eNOS and ras gene polymorphisms to initial peritoneal transport status in peritoneal dialysis patients. Nephron Clin Pract 2006; 104:c41 -6.[Medline]
46. Gillerot G, Goffin E, Michel C, Evenepoel P, Biesen WV, Tintillier M, et al. Genetic and clinical factors influence the baseline permeability of the peritoneal membrane. Kidney Int2005; 67:2477 -87.[Medline]
47. Dong C, Yoon W, Goldsmith–Clermont PJ. DNA methylation and atherosclerosis. J Nutr 2002;132 (Suppl 8):2406S -9S.[Abstract/Free Full Text]
48. Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, et al. Impact of inflammation on epigenetic DNA methylation—a novel risk factor for cardiovascular disease? J Intern Med 2007; 261:488 -99.[Medline]

This article has been cited by other articles:

				H. Y. Choi, J. E. Lee, S. H. Han, T. H. Yoo, B. S. Kim, H. C. Park, S.-W. Kang, K. H. Choi, S. K. Ha, H. Y. Lee, et al. Association of inflammation and protein-energy wasting with endothelial dysfunction in peritoneal dialysis patients Nephrol. Dial. Transplant., November 19, 2009; (2009) gfp598v1. [Abstract] [Full Text] [PDF]

				L. S. Aroeira, E. Lara-Pezzi, J. Loureiro, A. Aguilera, M. Ramirez-Huesca, G. Gonzalez-Mateo, M. L. Perez-Lozano, P. Albar-Vizcaino, M-A. Bajo, G. del Peso, et al. Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane J. Am. Soc. Nephrol., March 1, 2009; 20(3): 582 - 592. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by García–López, E. Articles by Stenvinkel, P. Search for Related Content PubMed Articles by García–López, E. Articles by Stenvinkel, P.