Phosphorus Control
Figure 2: Calcium Acetate/Magnesium Carbonate (OsvaRen®) Versus Sevelamer-hydrochloride (Renagel®) in Haemodialysis Patients Study CaMg and Sevelamer Groups
A 2.5
Another alternative strategy to control serum phosphate levels while reducing the calcium dose is to use magnesium compounds, such as magnesium carbonate, alone or in combination with calcium salts. As with calcium and phosphate, magnesium levels can be markedly raised in CKD.69
Magnesium has a lower affinity for phosphate than that of aluminium or calcium but lower intestinal absorption results in greater amounts being available for binding in the gut lumen.70 Magnesium-containing compounds are not widely used in stage 5 CKD due to concern about hypermagnesaemia and possible gastrointestinal symptoms.71
Studies have shown, however, that 2.0
magnesium can be administered to many patients with stage 5 CKD without acute and medium-term side effects12,71,72
and that it can 1.5 01 23 5 7 9 CaMg B 1.3 13 Week Sevelamer-HCL 17 21 25
Magnesium carbonate has been repeatedly shown to be an effective phosphate binder.71,72,74
This was more recently demonstrated in
the Calcium acetate/magnesium carbonate (OsvaRen®) versus sevelamer-HCL (Renagel®) (CALMAG) study, in which patients receiving HD (n=255) were randomised to 435 mg calcium acetate/235 mg magnesium carbonate (CaMg) or 800 mg sevelamer- HCL for 24 weeks.12
1.2
reduce the total calcium intake when replacing other phosphate binders. The use of newer formulations containing magnesium carbonate has resulted in less diarrhoea than earlier formulations that contained magnesium hydroxide.73
The CaMg treatment was non-inferior to 1.1 1.0 1 2 3 5 7 9 CaMg C
1.0 1.2 1.4 1.6 1.8 2.0
0.8 01 2 3 5 7 9 CaMg 13 Week Sevelamer-HCL
A: Serum phosphate over 24 weeks (n=105 and 99); B: Total serum calcium (n=122 and 122) (full analysis set [FAS]); p=0.0032 (analysis of covariance [ANCOVA]); C: Serum magnesium (n=122 and 122) (FAS); p<0.0001 (ANCOVA). HCL = hydrochlorid e. Source: de Francisco et al., 2010.12
Secondly, combinations of calcium-based phosphate binders and newer calcium-free compounds are frequently given to patients, primarily for efficacy and for control of serum calcium levels but also for economic reasons. In such combinations, the dose of calcium is reduced and supplemented by a partial dose of a non-calcium phosphate binder.
98 17 21 25 13 Week Sevelamer-HCL 17 21 25
sevelamer-HCL for phosphate control below 5.5 mg/dL (≤1.78 mmol/L) (see Figure 2) and was significantly better in terms of serum phosphate control over time (p=0.0042). Treatment with CaMg reached the KDIGO target serum phosphate of ≤4.5 mg/dL [≤1.45 mmol/L] at a significantly higher number of visits than with sevelamer-HCL (p=0.0198). After 25 weeks, there was no difference in increases in ionised calcium levels between treatments (p=0.9173); an increase in total serum calcium levels in the CaMg group was statistically significant, but clinically negligible (treatment difference 0.0477 mmol/L (0.1913 mg/dL), p=0.0032). Serum magnesium levels remained unchanged in the sevelamer-HCL group and increased significantly, yet without symptoms of hypermagnesaemia in the CaMg group (treatment difference 0.2597 mmol/L, p<0.0001). Adverse event incidence was similar between groups but gastrointestinal symptoms were more frequent with sevelamer-HCL.
In both groups in the CALMAG study, iPTH decreased until week nine due to the phosphate lowering effects of both binders. After week nine, intact parathyroid hormone (iPTH) increased significantly in the sevelamer-HCL group (p=0.0242) but decreased slightly and insignificantly in the CaMg group (p=0.0768). At week 25, the mean iPTH level was 64.4773 pg/mL lower in the CaMg group (p=0.0085). Thus, CaMg did not suppress PTH beyond the effect of phosphate lowering.12
The CALMAG study also showed changes in bone markers such as bone alkaline phosphatase (BAP), which were significantly lower in the CaMg group than in the sevelamer-HCL group at week 25 (ANCOVA p<0.001 for all markers). CaMg appeared to stabilise bone turnover by moderately correcting some elevated bone markers, such as beta-crosslaps and preventing a continuous increase in other markers, while continuous increases of all markers were observed in the sevelamer-HCL group. Although the ideal levels of bone markers in dialysis patients remain to be established, CaMg does not appear to over-activate or over-suppress bone turnover. The Ca/Mg combination therefore could offer an alternative phosphate binder option whilst restricting the dose of calcium.12
EUROPEAN NEPHROLOGY
Serum magnesium (mmol/L)
Ionised serum calcium (mmol/L)
Serum phosphorus (mmol/L)
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92