m2 ), who had a hemoglobin less than 11 g/dL at entry. Enrolled subjects were randomly assigned to epo therapy treatment protocols designed to achieve a target hemoglobin level of either 13.5 (n ¼ 715) or 11.3 g/dL (n ¼ 717). The study was terminated prematurely because of higher mortality rates and adverse events in the group with higher targeted Hgb levels [14]. Consequently, the US Food and Drug Administration (FDA) issued an alert recommending a target Hgb level between 11 and 12 g/dL in CKD patients, although more data will be needed to determine the optimal Hgb level to maximize quality of life and reduce excess mortality from anemia-related complications. In summary, despite the clear benefit from treatment of anemia on morbidity and mortality in CKD patients, a significant proportion of anemic CKD patients do not receive adequate treatment before dialysis to achieve current FDA-recommended targets [15], and half of all CKD patients with anemia do not receive treatment with erythropoietin [16]. The precise target level for Hgb CHRONIC KIDNEY DISEASE AND ITS COMPLICATIONS 331 has not been definitively determined, but following FDA recommendations is prudent. CKD-associated mineral and bone disorders The term ‘‘CKD-associated mineral and bone disorders’’ comprises abnormalities in bone and mineral metabolism and/or extraskeletal calcification secondary to CKD pathophysiology [17,18]. Renal osteodystrophy is the spectrum of histologic changes that occur in bone architecture of patients with CKD. The kidney is the primary site for phosphate excretion and 1-a-hydroxylation of vitamin D. CKD patients develop hyperphosphatemia as a result of inadequate 1,25 dihydroxy-vitamin D levels that reflect reduced synthesis from parenchymal scarring. In addition, renal phosphate excretion is reduced. Together, both processes cause serum calcium levels to fall resulting in increased secretion of parathyroid hormone (secondary hyperparathyroidism). Parathyroid hormone has a phosphaturic effect. It also increases the calcium levels by increasing bone resorption and promoting 1-a-hydroxylation of 25-hydroxy vitamin D synthesized by the liver (limited effect because of reduced kidney reserve from scarring). Rising phosphorus levels are almost universally observed in stage 3 CKD patients. However, secondary hyperparathyroidism often begins to distort bone architecture earlier before serum phosphorus is noted to be abnormal, indicating that phosphate binder therapy needs to be initiated when eGFRs have declined below 50 mL/min per 1.73 m2 . Changes in bone architecture can be caused by either a high bone turnover state or a low bone turnover state. Four types of bone phenotypes (renal osteodystrophy) can be diagnosed in CKD patients: osteitis fibrosa cystica (high bone turnover with secondary hyperparathyroidism), osteomalacia (low bone turnover and inadequate mineralization, primarily related to diminished vitamin D synthesis), adynamic bone disorder (low bone turnover from excessive suppression of the parathyroid glands), and mixed osteodystrophy (with elements of both high and low bone turnover). The predominant type of renal osteodystrophy and CKD-mineral and bone disorder differs between predialysis and endstage renal disease patients. In predialysis patients, high bone turnover bone disease is most prevalent. In contrast, low bone turnover predominates in dialysis patients. Patients with low turnover disease represent most cases of renal osteodystrophy [19]. The cause of this prevalent bone phenotype results from oversuppression of parathyroid hormone and high calcium dialysate concentrations[20]. Acidosis, the suppressive effect of phosphate retention on renal synthesis of 1,25 dihydroxy-vitamin D synthesis, and absence of the physiologic inhibitory effect of vitamin D on parathormone secretion are also minor factors that contribute to the low turnover bone disease in CKD patients [21]. CKD-associated mineral bone disorders significantly increase mortality in CKD patients. In fact, hyperphosphatemia is one of the most important 332 THOMAS et al risk factors associated with cardiovascular disease in CKD patients [22]. The exact mechanism underlying this association remains unclear. It is believed to be related to hyperparathyroidism [23] and vascular calcification, which results from high phosphorus levels [24]. Use of calcium-based binders and excessive vitamin D therapy [25] may also contribute to the vascular calcification and its attendant cardiovascular mortality. Patients on hemodialysis who have a plasma phosphorus level above the K/DOQI guideline target levels have a 40% higher mortality rate when compared with those having target levels [26]. The principal goal of the treatment of CKD-associated bone and mineral disorders is phosphorous level reduction [1]. Initial treatment restricts dietary phosphorus intake when phosphate or parathyroid hormone levels begin to rise. According to K/DOQI guidelines (http://www.kidney.org/ professionals/KDOQI/guidelines_bone/index.htm), serum phosphorus levels should be maintained between 2.7 and 4.6 mg/dL in patients with stages 3 and 4 CKD, and between 3.5 and 5.5 mg/dL in individuals with stage 5 CKD. Different classes of phosphate binders can be used to accomplish this goal. For chronic