**5.3 PTH and anemia**

Anemia is a highly prevalent finding in patients with CKD and is considered as a sign of poor prognosis as it is associated with increased cardiovascular disease, hospitalization and mortality. Up to 100% of patients with stage 5 KCD have anemia. It is of a different pathophysiological basis although erythropoietin deficiency is the most recognized underlying cause. Other causes include resistance to erythropoietin, bone marrow fibrosis and shortened life span of red blood cells [45]. Secondary hyperparathyroidism and the associating high PTH level have been linked to these suggested causes of anemia. Bone marrow fibrosis has been detected in both primary and secondary hyperparathyroidism with consequent anemia which is significantly improved after parathyroidectomy making the correlation of bone marrow fibrosis and secondary hyperparathyroidism highly suggestive [46, 47]. Fortunately, bone marrow fibrosis has been reversed after parathyroidectomy. The direct inhibitory effect of PTH on erythropoietin synthesis has been confirmed by many authors when plasma concentration of erythropoietin increased significantly after parathyroidectomy reaching to 10-folds higher than its preoperative concentration within 2 weeks or even less; the molecular pathophysiology of this inhibitory effect is not yet known [48, 49]. Shortened lifespan of red blood cells has been observed in patients with CKD as a cause of anemia and it was linked to the high plasma PTH due to its role in increasing median osmotic fragility of red blood cells with consequent anemia [50]. Cinacalcet hydrochloride, a calcimimetic drug, which is used as a medical treatment of secondary hyperparathyroidism has been associated with improvement in hemoglobin level and necessitating fewer doses of erythropoiesis-stimulating agents to correct anemia [51, 52]. Similarly, patients with CKD and secondary hyperparathyroidism treated with the active form of vitamin D (calcitriol) have shown a similar response to that of cinacalcet with improved hemoglobin level and less doses of erythropoietin required to control anemia [53].
