therapy, calcium-based formulations for management of CKDassociated hyperphosphatemia are the most widely used class of phosphate binders and have supplanted aluminum-based phosphate binders since aluminum-associated toxicities have been recognized. However, calciumbased phosphate binders can induce hypercalcemia, which increases the tissue calcium deposition, especially in the presence of hyperphosphatemia. If indicated (eg, a CKD patient with hypercalcemia), short-term usage of aluminum-based phosphate binders remains appropriate, although alternative calcium-free, phosphates have been developed, such as the nonabsorbable agent sevelamer. This agent has the advantage of lacking calcium or aluminum. In addition to phosphate binders, several other classes of drugs have been developed to manage CKD-associated mineral disorder. Given the reduced 1-hydroxylation of vitamin D by the failing kidney, vitamin D and its related compounds may be needed to raise the serum calcium concentration sufficiently to suppress parathyroid hormone secretion. Patients can also be given calcimimetics, agents that increase the calcium sensitivity of the calciumsensing receptor expressed by the parathyroid gland, down-regulating parathyroid hormone secretion and reducing hyperplasia of the parathyroid gland. The K/DOQI guidelines provide specific management recommendations for use of these agents and the interested reader is referred to the Web link provided for details. Cardiovascular risk The increased cardiovascular risk associated with end-stage renal disease has been well established, and estimated cardiovascular mortality rates are 10- to 100-fold higher among dialysis patients than age- and sex-matched CHRONIC KIDNEY DISEASE AND ITS COMPLICATIONS 333 individuals in the general population [27]. The cardiovascular risk associated with renal impairment increases earlier in the course of kidney disease progression than was initially hypothesized. More specifically, there is evidence that even mild to moderate degrees of renal impairment are associated with increased cardiovascular risk. Many traditional cardiovascular risk factors, documented in the general population, contribute to cardiovascular risk in CKD patients. In fact, many Framingham risk factors are more prevalent among individuals with CKD than among those with normal renal function. In addition, nontraditional risk factors, specific to CKD patients, also contribute to the burden of cardiovascular disease (discussed later in this article). Hypertension is a traditional cardiovascular risk factor that contributes to the cardiovascular risk associated with CKD. Muntner and colleagues demonstrated that patients with hypertension are at increased risk for new or recurrent cardiovascular events in individuals with stage 2-3 CKD [28]. Systolic blood pressure is more strongly associated with cardiovascular death in dialysis patients than either pulse or diastolic pressure [29]. However, a U-shaped relationship exists between systolic blood pressure and mortality in which high or low systolic blood pressures appear to be associated with increased mortality rates in stage 5 CKD patients. Low systolic pressures may identify a sicker group of patients rather than being an etiology for excess mortality. K/DOQI guidelines recommend target blood pressure less than 130/85 mm Hg for all patients with kidney disease and less than 125/75 mm Hg for patients with urinary protein excretion greater than 1 g/24 h. Detailed treatment recommendations are beyond the scope of this review. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, given their renal protective effects, are optimal first-line agents in patients with proteinuric (O 1 g/24 h), progressive diabetic and nondiabetic renal disease. Diabetes is associated with adverse outcomes in all stages of CKD [30]. Moreover, lower fasting plasma glucose and/or glycated hemoglobin levels are associated with lower risk of all-cause mortality and reduced cardiovascular death of borderline significance in patients with moderate to severe renal impairment. The presence of LVH, a complication that increases in relation to progressively lower levels of eGFR, is also a cardiovascular risk determinant in CKD patients. Anemia and hypertension are two CKD-associated complications hypothesized to play a role in the development of LVH [10]. In a prospective cohort of 2423 patients with stage 3 to 4 CKD, investigators noted an independent risk of LVH for the composite end point of myocardial infarction and fatal coronary heart disease (CHD). Patients were followed over a period of 102 months. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes hazard ratio (HR 1.67; 95% CI 1.34 to 2. 07). Tobacco use is also associated with increased mortality and incidence of heart failure among patients with stage 5 CKD [31]. 334 THOMAS et al Several cardiovascular risk factors associated with CKD are unique to patients with this disease (nontraditional risk factors). Anemia, which was discussed earlier, is a risk factor for adverse cardiovascular outcomes in CKD patients. Abnormal serum phosphate levels, calcium-phosphate ion product, and parathyroid hormone levels are independent cardiovascular risk factors in the setting of stage 5 CKD [32].