**2. Treatment of hyperphosphatemia**

Declining renal function inevitably causes phosphorus retention due to decreased renal phosphorus clearance. This mechanism starts early in chronic kidney disease. However, hyperphosphatemia is prevented until the late stages of chronic kidney disease by an increase in FGF23 and PTH which control phosphorus homeostasis for a definite time. Initially, phosphorus retention stimulates FGF23 and PTH secretion, which in turn suppress

Management of Secondary Hyperparathyroidism in Hemodialysis Patients 335

class. Although no placebo-controlled randomized trial has been done so far to prove that reduction in serum phosphorus by the use of phosphate binders improves patient outcomes, a recent prospective observational study in a large number of incident dialysis patients has shown that the use of any phosphate binder (versus none) offers a clear survival benefit independent of absolute serum phosphorus concentration and co-medication (Isakova et al.,

Available phosphate binders include the calcium salts calcium acetate and calcium carbonate, aluminium hydroxide, the polymeric anion-exchange resins sevelamer hydrochloride and sevelamer carbonate, lanthanum carbonate and the newer so far not well studied compounds ferric citrate, SBR759 (iron-based), magnesium/calcium carbonate and magnesium carbonate/calcium acetate. They differ in composition, phosphate-binding capacity, form and have specific potential advantages and disadvantages, which are

Considering the different agents there are no data at present to favour one phosphate binder, because there is no proven superiority of any phosphate binder or binder class for relevant clinical outcomes. According to a recent systematic review and meta-analysis of available randomized controlled trials all phosphate binders decrease serum phosphorus levels compared with placebo. The newer drugs sevelamer hydrochloride and lanthanum carbonate do not result in superior control of biochemical parameters compared with calcium salts. In contrast, in head-to-head studies calcium salts enable a greater reduction of serum phosphorus than sevelamer hydrochloride. Whereas both calcium salts (calcium acetate and carbonate) do not differ with regard to serum calcium levels, sevelamer hydrochloride and lanthanum carbonate are associated with significantly lower rates of treatment-related hypercalcemia, which may result in decreased cardiovascular calcification. However, the finding of slower or less progression of cardiovascular calcification in sevelamer-treated patients is inconsistent across the studies. Studies revealed no difference in PTH suppression when comparing calcium acetate with calcium carbonate or lanthanum

2009).

**Binder source** 

**Calcium carbonate** 

**Calcium acetate** 

**Form Content** 

tablet, capsule, chewable, gum, liquid

capsule, tablet

**(mineral/metal/element)** 

200 mg elemental Ca2+ per 500 mg carbonate (40% elemental Ca2+)

126.7 mg elemental Ca2+ per 500 mg tablet, 169 mg elemental Ca2+ per 667 mg capsule (25% elemental Ca2+)

**Phosphatebinding capacity** 

> 1500 to 3500 mg (3–7 tablets)

> 3000 to 6000 mg (6 to 12 tablets)

39 mg phosphate per 1 gramm calcium carbonate

45 mg phosphate per 1 gramm calcium acetate

**Daily dose Advantages Disadvantages** 

potential for hypercalcemia and hypercalcemiaassociated risks, gastrointestinal side

potential for hypercalcemia and hypercalcemiaassociated risks, gastrointestinal side effects, more costly than carbonate

effects

effective phosphatebinding, inexpensive, readily available, longterm experience

effective phosphatebinding, potentially higher binding capacity and lower Ca2+ absorption than carbonate, inexpensive, long-term experience

summarized in Table 1.

renal phosphorus reabsorption and increase renal phosphorus excretion. FGF23 also suppresses calcitriol (1,25(OH)2D3) production, which diminishes intestinal phosphorus absorption but allows increases in PTH levels. Whereas FGF23 suppresses PTH secretion in normal parathyroid glands, resistance to its effect occurs with further loss of kidney function because of decreased Klotho and FGF receptor 1 expression in the parathyroid glands and the kidney. Thus, as chronic kidney disease progresses to late stages, these homeostatic mechanisms are inevitably overwhelmed, hyperphosphatemia ensues, and the levels of PTH and FGF23 increase progressively (Cunningham et al., 2011).

Robust observational data show a clear association of higher serum phosphorus levels with cardiovascular events and mortality (Block et al., 1998, 2004). The exact threshold above which risk significantly increases is not definitely known and varies across the studies from 5.0 to 7.0 mg/dL (1.6 to 2.3 mmol/L) (Covic et al., 2009). However, it has never been determined in randomized placebo-controlled trials whether treating hyperphosphatemia to specific target ranges improves clinical patient outcomes. The KDIGO guidelines therefore suggest to decrease serum phosphorus levels toward the reference range in patients with chronic kidney disease 5D (KDIGO, 2009).

Therapeutic interventions to treat hyperphosphatemia include restriction of dietary phosphorus intake, administration of phosphate binders and increasing the frequency or length of dialysis sessions.
