Director of Department of Nephrology and Dialysis
President of the European Renal Association
Lucia Del Vecchio
Department of Nephrology and Dialysis
A Manzoni Hospital
Half of all deaths in dialysis patients are of cardiovascular origin and about one third of hospitalisations are due to cardiovascular disease.(2) The understanding and proper management of the determinants of cardiovascular disease in the dialysis population are therefore a major focus of nephrological care.
The pathogenesis of cardiovascular damage in dialysis patients is far more complex than in the general population, since risk factors not only include those identified in the general population, but also additional risk factors, which are typical of chronic kidney disease (CKD) or of the dialytic treatment itself (Table 1). The prevalence of traditional risk factors among dialysis patients is far higher than in the general population. Indeed, these patients are very often elderly, affected by hypertension and diabetes (the two commonest causes of endstage renal disease in many countries) and by metabolic derangement caused by renal failure (eg, secondary hypertension, dislipidaemia, coagulation equilibrium imbalance, hyperhomocysteinaemia and systemic inflammation). In addition, haemodynamic and metabolic risk factors which are peculiar to CKD and dialysis, including in particular anaemia, hyperparathyroidism, and increased oxidant stress,(3) further enhance the cardiovascular risk.
The prevalence of echocardiographic signs and/or clinical manifestations of CVD is already high at the beginning of renal replacement treatment, suggesting that mechanisms leading to cardiovascular disease have been operating since the earliest stages of CKD.(4,5) Therefore the prevention of CVD should begin as early as possible during the course of CKD, taking care of the cardiovascular risk factors optimally. These are the reasons why a timely referral of CKD patients to nephrological care is of crucial importance, being able to strongly influence the patient outcome in a favourable manner.(6)
Hypertension, a well-established cardiovascular risk factor in the general population, is very common among CKD patients. Although the relationship between hypertension and outcome in dialysis patients has been a controversial issue for many years, the results of large observational studies suggest that hypertension plays a major role in determining cardiac damage also in dialysis patients (mainly because of the development of left ventricular hypertrophy); moreover, the control of blood pressure in hypertensive haemodialysis patients leads to a substantial regression of left ventricular hypertrophy. Considering the detrimental consequences of left ventricular hypertrophy on patients’ morbidity and mortality, adequate blood pressure control must therefore be a major objective in the management of patients with CKD also during the dialytic phase. Given that hypertension in dialysis patients is essentially volume sensitive, it is of paramount importance to limit the interdialytic weight gain and to keep patients as close as possible to their dry weight. In the meantime, it is crucial to manage antihypertensive drugs properly, in order to achieve blood pressure control in the interdialytic phase, while avoiding hypotensive episodes during haemodialysis sessions due to a prolonged effect of antihypertensive drugs. At the moment there is no proof that any class of antihypertensive drugs is superior to another in preventing cardiovascular disease in dialysis patients when blood pressure is adequately controlled. However, ACE-inhibitors and angiotensin II receptor antagonists can ameliorate the haemodynamic profile and protect from left ventricular remodelling, independently from their ability to reduce blood pressure. Furthermore, the results of the HOPE study, showing that ACE-inhibitors led to a better prognosis in patients at high cardiovascular risk than other antihypertensive drugs, suggest the elective use of these drugs in dialysis patients.
Anaemia is, together with hypertension, the main contributor to the development of left ventricular hypertrophy in dialysis patients (see Figure 1) and is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality, in such patients;(7) its correction leads to significant improvements in cardiovascular status, quality of life and long-term prognosis. The current guidelines for the management of anaemia in patients with CKD recommend a target haemoglobin of 11–12g/dl, but the debate is still open as to the possible benefits and safety of increasing haemoglobin above 12g/dl or even normalising it, at least in selected categories of patients.
Calcium, phosphate, hyperparathyroidism and calcium x phosphate product are also important risk factors for cardiovascular complications and death.(8) Nowadays we are well aware of the risk of toxicity of phosphate binders containing aluminium (anaemia, dementia, adynamic bone disease) and that the excessive use of calcium carbonate (more than 1.5g per day) is associated with an increase in the risk of cardiovascular calcifications. The very recent availability of phosphate binder not containing either calcium or aluminium, such as sevelamer hydrochloride and in the near future lanthanum carbonate, could solve this problem. Indeed Chertow et al showed that the use of sevelamer was able to significantly reduce cardiovascular calcifications in comparison with the use of calcium carbonate in haemodialysis patients.(9) Moreover, calcimimetics and new vitamin D analogues will be available very soon, further reducing the risk of secondary hyperparathyroidism without the problem of increasing serum calcium and phosphorus levels and therefore the risk of cardiovascular calcifications.
- Levey AS, Beto JA, Parfrey PS, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? Am J Kidney Dis 1998;32:85.
- US Renal Data System: 2002 annual data report. Bethesda, MD: The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2002.
- Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272-80.
- Levin A, Thompson CR, Ethier J, et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis 1999;34:125-34.
- Culleton BF, Larson MG, Wilon PWF, et al. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int 1999;56:2214-9.
- Locatelli F, Del Vecchio L, Pozzoni P. The importance of early detection of chronic kidney disease. Nephrol Dial Transplant 2002; 17(Suppl 11):2-7.
- Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anaemia on cardiomyopathy, morbidity and mortality in end-stage renal disease. Am J Kidney Dis 1996;28:53-61.
- Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 31:607-17.
- Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245-52.