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Use of Magnesium Hydroxide and Low Magnesium Dialysate Does Not Permit Reduction of Aluminum Hydroxide During Continuous Ambulatory Peritoneal Dialysis
Use of Magnesium Hydroxide and Low Magnesium Dialysate Does Not Permit Reduction of Aluminum Hydroxide During Continuous Ambulatory Peritoneal Dialysis Anne E. Jennings, MD, Magnus Bodvarsson, MD, Grazyna Galicka-Piskorska, MD, Anne S. Diefendorf, RD, Gertrude M. Simon, RN, and Andrew S. Levey, MD • In an effort to reduce the ingestion of aluminum in phosphate-binding antacids, we treated seven patients on continuous ambulatory peritoneal dialysis (CAPO) with low magnesium dialysate and phosphate binders containing both aluminum and magnesium hydroxide. The total amount of phosphate binders prescribed was adjusted to maintain the serum phosphorus at normal levels. The dose of magnesium hydroxide was limited by intolerable gastrointestinal side effects in six of the seven patients. One patient also developed symptomatic hypermagnesemia. When magnesium hydroxide was prescribed in tolerable doses, the mean aluminum dose was not significantly decreased compared with the dose when taking aluminum hydroxide alone. We conclude that substitution of magnesium hydroxide for aluminum hydroxide as a phosphate binder fails to reduce the dose of aluminum in most patients on CAPO. © 1986 by the National Kidney Foundation, Inc. INDEX WORDS: Peritoneal dialysis; aluminum; magnesium; phosphate binders.
A
LUMINUM TOXICITY is recognized as an important cause of morbidity in patients on dialysis. Osteomalacia, anemia, and dementia have been associated with increased levels of aluminum in tissues and serum. I - 3 Although aluminum toxicity was first recognized in patients undergoing hemodialysis with dialysate containing high levels of aluminum, it is now known that toxic levels of aluminum also can accumulate from gastrointestinal (GI) absorption of aluminum contained in phosphate-binding antacids. 4 - 7 These findings have led to a search for phosphate binders not containing aluminum. Some investigators have suggested using magnesium hydroxide in patients treated with hemodialysis8; however, others have reported elevated magnesium levels as a complication of this therapy. 9. \0 The risks of hypermagnesemia in dialysis patients are well known and include neurologic impairment and defective bone mineralization. 1o. 11 The recent availability of peritoneal dialysate containing a low concentration of magnesium prompted us to study whether the use of this From the Division of Nephrology, Department of Medicine, Department of Nursing, and the Dietary Department, New England Medical Center and Tufts University School of Medicine, Boston. Address reprint requests to Andrew S. Levey, MD, Division of Nephrology, New England Medical Center, Box 784, 171 Harrison Ave, Boston, MA 02111. © 1986 by the National Kidney Foundation, Inc. 0272-6386/86/0709-0009$03.00/0 192
dialysate preparation in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) would permit substitution of magnesium hydroxide for aluminum hydroxide, without the development of hypermagnesemia. In our experience, this therapy caused intolerable GI side effects and failed to reduce aluminum intake in most patients. PATIENTS AND METHODS We prospectively studied seven patients with end-stage renal disease treated with CAPD. Their average age was 44 years (range 26 to 68 years); six patients were male, and one was female. The patients had initiated CAPD with coventional peritoneal dialysate conIaining 1.5 mEq/L magnesium (Dianeal; Baxter Travenol, Deerfield, Ill) and were prescribed aluminum-containing phosphate binders (Basaljel [Wyeth, Philadelphia, Pal, Alucaps [Riker, Northridge, Calif], or Dialume [Armour Pharmaceutical Co, Tarrytown, NY]). The duration of CAPD prior to the study was 26 months (range 5 to 42 months). None had symptoms or laboratory findings of osteomalacia or dementia. Informed consent was obtained in all patients. The study was conducted in three phases. In the first phase, patients remained on their usual dialysis regimen and completed a 1- to 3-month baseline evaluation. In the second phase, patients were instructed to begin using peritoneal dialysate containing 0.5 mEq/L magnesium (PD2; Baxter 1favenol, Deerfield, TIl). They also were instructed to substitute an antacid containing magnesium hydroxide for part of their phosphatebinder dose. We initially recommended Maalox II (Rorer, Fort Washington, Pa), containing 166.8 mg magnesium and 248 mg aluminum per tablet, because of its high magnesium content and high potency as a phosphate binder. 12 During the next 1 to 3 months, the dose of Maalox II was increased, the dose of aluminum hydroxide was decreased, and the serum phosphorus
American Journal of Kidney Diseases. Vol VIII, No 3 (September). 1986: pp 192-195
MAGNESIUM HYDROXIDE AS PHOSPHATE BINDER
193
level was maintained within normal limits. The dose of Maalox II was increased until other aluminum hydroxide preparations had been discontinued, until the patient developed GI intolerance (diarrhea), or until the serum magnesium level rose to 3.5 mEq/L or higher. rNe chose this value for serum magnesium because previous studies have not shown toxicity in patients on dialysis with levels below this value. 8) In the third phase, patients were followed for an additional 1 to 3 months. If side effects from magnesium hydroxide had occurred in the second phase, the dose of Maalox II was decreased until side effects were tolerable and the aluminum hydroxide dose was increased in order to maintain a normal serum phosphorus level. In all three phases, patients were seen at 2- to 6-week intervals. The intake of phosphate binders, symptoms of hypomagnesemia or hypermagnesemia, bowel habits, and serum magnesium, phosphorus, and calcium levels were monitored at each visit. Phosphorus intake was assessed by dietary recall at the beginning and end of the study. Results obtained during all three phases were compared. Serum aluminum was measured in all patients during the baseline evaluation using a PerkinElmer 5000 rNaitham, Mass) atomic absorption spectrophotometer with a graphite furnace. Normal values for similar techniques are up to 7 /Lg/L6.13; values for dialysis patients ingesting aluminum hydroxide usually are in the range from 30 to 300 /Lg/L.7.I3-1' Data are reported as the mean ± SD. Comparisons were made by the paired t test. A value for P < .05 was considered significant.
Aluminum Dose (g/d)
1 2 3 4 5 6 7
3.63 3.83 4.15 4.15 3.11 1.27 1.90 3.15 ± 1.14
Mean ± SD
GI
Symptoms N N N N C C N
~
••
.It.
•
Control
Peak Mg dose
Tolerable Mg dose
3
•
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•
5
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:::!E :::>
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• •
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4 3 Peak Mg dose
Tolerable Mg dose
Fig 1. Serum magnesium and phosphorus levels. (A) The serum magnesium level during the three phases of the study (see text). (B) The serum phosphorus levels during the same phases. Black circles indicate values for individual patients. Means are indicated by a short line. Normal values are indicated by the shaded area.
Aluminum Dose, Magnesium Dose, and GI Symptoms
Phase 1: Aluminum Hydroxide Alone Patient No.
u; z
w
00
The serum aluminum levels were elevated in all patients at the onset of the study (185 ± 166 p.g/L; range 50 to 495 p.g/L). Table 1 and Fig 1 show the serum magnesium and phosphorus levels, dose of aluminum and magnesium, and GI symptoms for the seven patients during conventional therapy, during treatment with low magnesium dialysate and magnesium hydroxide at the peak dose, and at a dose tolerable to the patients. The serum magnesium concentration, serum phosphorus concentration, and aluminum dose did not differ significantly in these patients during treatment with the
•
4 :::!E :::>
a: w
RESULTS
Table 1.
A
Phase 2: Peak Dose Magnesium Hydroxide Aluminum Dose (gJd)
Magnesium Dose (gJd)
3.10 2.47 3.18 4.37 3.18 1.68 2.42 2.91 ± 0.84
1.00 0.17 1.50 1.00 1.50 1.17 1.33 1.10 ± 0.46
Abbreviations: D, diarrhea; C, constipation; N, none.
Phase 3: Tolerable Dose Magnesium Hydroxide GI
Symptoms D D D D D N D
Aluminum Dose (gJd)
Magnesium Dose (gJd)
3.10 0 3.83 0 2.33 1.00 3.74 0.50 3.50 1.00 1.68 1.17 2.28 1.00 2.92 ± 0.83 0.67 ± 0.50
GI
Symptoms N N N N N N N
194
JENNINGS ET AL
three regimens (P > .2). Serum calcium levels and dietary phosphorus intake also remained unchanged during the study (results not shown). Thus, there was no overall benefit of the low magnesium dialysate with magnesium-containing phosphate binders in reducing the mean aluminum dosage. There were no apparent side effects of the low magnesium dialysate. None of the patients developed hypomagnesemia. However, six of the seven patients had side effects from magnesium hydroxide. The dose of magnesium-containing phosphate binders was limited by diarrhea in six patients. The maximum tolerable dose of magnesium was 1.17 g/d. One patient (no. 1) developed diarrhea and symptomatic hypermagnesemia (Mg concentration 4.0 mEq/L) , manifested by muscle weakness, absent deep tendon reflexes, and slurred speech. These symptoms disappeared when magnesium hydroxide was discontinued. Attempts to reinstitute magnesium hydroxide in a lower dose resulted in recurrent diarrhea and mild asymptomatic hypermagnesemia. Eventually, magnesium hydroxide had to be discontinued altogether. One other patient (no. 2) also was unable to tolerate even small doses of magnesium-containing antacids, because of diarrhea. The dose of aluminum decreased substantially in only one patient (no. 3). However, the aluminum intake remained high. In the remaining four patients, aluminum dosage either decreased slightly (no. 4) or increased slightly (nos. 5, 6, and 7). In the five patients able to tolerate magnesium hydroxide, the dose of magnesium was 0.93 ± 0.25 g/d. The aluminum dose in these five patients was 2.92 ± 1.31 gld prior to beginning magnesium hydroxide and 2.71 ± 0.88 gld while taking magnesium hydroxide (P > .2). DISCUSSION
The widespread recognition of the toxicity of aluminum had led to a search for means of reducing the intake of aluminum contained in phosphate binders. Guillot et al suggested magnesium hydroxide might be safely used as a phosphate binder in hemodialysis patients. 8 Others, however, have warned of the potential risks of this therapy and advised against it. 9, 10 The safety and effectiveness of magnesium hydroxide as a phosphate binder in CAPD patients has not been studied.
In order to reduce the dose of aluminum hydroxide in CAPD patients, we prescribed phosphate binders with a mixture of aluminum and magnesium hydroxide and used a dialysate with a low magnesium concentration. In six of seven patients, the dose of magnesium hydroxide was limited by GI side effects. One patient also developed symptomatic hypermagnesemia. Two patients were unable to tolerate any magnesium hydroxide because of diarrhea. Five patients were able to tolerate small doses of magnesium hydroxide (0.5 to 1.17 g/d) , but in only one patient did the aluminum dose decrease greatly. In this patient, however, the dose of aluminum remained 2.33 gld, a dose that is associated with high serum aluminum levels in CAPD patients. 7 In our study, as in the study by Guillot et al, 8 the maximal tolerable dose of magnesium was approximately 1 g/d. Higher doses led to diarrhea and hypermagnesemia. In our study, the magnesium dose exceeded 1 gld in only one patient, and in ths patient, other aluminum hydroxide preparations could be eliminated. Nonetheless, the aluminum dose in this patient was not decreased. One explanation for this failure to reduce aluminum intake might be that the combination of magnesium and aluminum hydroxide is not as potent a phosphate binder as is aluminum hydroxide alone. Thus, in our experience, the combination of low magnesium peritoneal dialysate and phosphate binders containing both magnesium and aluminum hydroxide is not useful in decreasing the aluminum dosage in most patients on CAPD. Only a small subset of patients (one in seven in our experience) are able to reduce aluminum intake significantly. Most patients, however, develop GI symptoms and are able to tolerate only small doses of magnesium hydroxide or none at all. Furthermore, there is a moderate risk of symptomatic hypermagnesemia. Totally eliminating magnesium from dialysate might reduce the risk of hypermagnesemia, but it is highly unlikely that this would improve GI tolerance. We conclude that magnesium-containing phosphate binders will not achieve the goal of reducing intake of aluminum in most patients. Recently, some investigators used calcium carbonate as the sole phosphate binder in order to avoid aluminum toxicity.5,16 Further clinical studies are indicated to discover potent and tolerable alternatives to aluminum hydroxide for patients on dialysis.
195
MAGNESIUM HYDROXIDE AS PHOSPHATE BINDER
ADDENDUM A recent study demonstrated the feasibility of substituting magnesium carbonate for aluminum hydroxide as a phosphate binder in patients treated by hemodialysis and a magnesium-free dialysate. 17 The dose of magnesium was 0.16 to 0.5 g/d and maintained the mean serum phosphorus at 5.5 to 6.0 mg/dL for 2 years. Aluminum hydroxide was discontinued and serum aluminum levels declined. The efficacy of lower doses of magnesium in this study may be related to differences in the phos-
phate-binding capacity of magnesium carbonate and magnesium hydroxide or to differences in intake and removal of phosphorus in patients treated by hemodialysis and CAPD.
ACKNOWLEDGMENTS We wish to thank Travenol Laboratories for providing custom-made PD2 solutions, Dr Clive Bach for assisting in the study, Andrew MacAulay and Joyce Ellis, Clinical Study Unit at New England Medical Center, for measuring aluminum (supported by GCRC Grant No. RR 00(54), and Drs Nicolaos E. Madias and John T. Harrington for reading the manuscript.
REFERENCES 1. Wills MR, Savory J: Aluminum poisoning: Dialysis encephalopathy, osteomalacia and anaemia. Lancet 2:29-33, 1983 2. Boyce BF, Fell GS, Elder HY, et al: Hypercalcemic osteomalacia due to aluminum toxicity. Lancet 2:1009-1013, 1982 3. Arieff AI, Cooper JD, Armstrong D, et al: Dementia, renal failure and brain aluminum. Ann Intern Med 90:741747, 1979 4. Committee of the European Dialysis and Transplant Association: Dialysis dementia in Europe. Lancet 2:190-192, 1980 5. Andreoli Sp, Bergstein JM, Sherrard OJ: Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 310:1079-1084, 1984 6. Kaehny WD, Hegg Ap, Alfrey AC: Gastrointestinal absorption of aluminum from aluminum containing antacids. N Engl J Med 296:1389-1390, 1977 7. Rottembourg J, Gallego JL, Jaudon MC, et al: Serum concentration and peritoneal transfer of aluminum during treatment by continuous ambulatory peritoneal dialysis. Kidney Int 25:919-924, 1984 8. Guillot Ap, Hood VL, Runge CF, et al: The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron 30:114117, 1982 9. Brunner FP, Thiel G: Re: The use of magnesium-contain-
ing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron 32:266, 1982 10. Randall RE, Cohen MD, Spray CC, et al: Hypermagnesemia in renal failure. Etiology and toxic manifestations. Ann Intern Med 61:73-88, 1964 11. Alfrey AC,Miller NL: Bone magnesium pools in uremia. J Clin Invest 52:3019-3027, 1973 12. Bailey GL, Vona JP: Pharmacodynamics in renal failure, in Bailey GL (ed): Hemodialysis: Principles and Practice. Orlando, Fla, Academic, 1972, pp 117-186 13. Oster 0: The aluminum content of human serum determined by atomic absorption spectroscopy with a graphite furnace. Clin Chern Acta 114:53-60, 1981 14. Fleming LW, Stewart WK, Fell GS, et al: The effect of oral aluminum therapy on plasma aluminum levels in patients with chronic renal failure in an area with low water aluminum. Clin Nephrol 17:222-227, 1982 15. Milliner DS, Nebeker HG, Ott SM, et al: Use of the deferoxamine test in the diagnosis of aluminum-related osteodystrophy. Ann Intern Med 101:775-780, 1984 16. Slatopolsky E, Weerts C, Lopez S, et al: Calcium carbonate is an effective phosphorus-binder in dialysis patients. Kidney Int 27:173, 1985 (abstr) 17. O'Donovan RO, Baldwin D, Hammer M, et al: Substitution of aluminum salts by magnesium salts in control of dialysis hyperphosphatemia. Lancet 1:880-882, 1986
A
LUMINUM TOXICITY is recognized as an important cause of morbidity in patients on dialysis. Osteomalacia, anemia, and dementia have been associated with increased levels of aluminum in tissues and serum. I - 3 Although aluminum toxicity was first recognized in patients undergoing hemodialysis with dialysate containing high levels of aluminum, it is now known that toxic levels of aluminum also can accumulate from gastrointestinal (GI) absorption of aluminum contained in phosphate-binding antacids. 4 - 7 These findings have led to a search for phosphate binders not containing aluminum. Some investigators have suggested using magnesium hydroxide in patients treated with hemodialysis8; however, others have reported elevated magnesium levels as a complication of this therapy. 9. \0 The risks of hypermagnesemia in dialysis patients are well known and include neurologic impairment and defective bone mineralization. 1o. 11 The recent availability of peritoneal dialysate containing a low concentration of magnesium prompted us to study whether the use of this From the Division of Nephrology, Department of Medicine, Department of Nursing, and the Dietary Department, New England Medical Center and Tufts University School of Medicine, Boston. Address reprint requests to Andrew S. Levey, MD, Division of Nephrology, New England Medical Center, Box 784, 171 Harrison Ave, Boston, MA 02111. © 1986 by the National Kidney Foundation, Inc. 0272-6386/86/0709-0009$03.00/0 192
dialysate preparation in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) would permit substitution of magnesium hydroxide for aluminum hydroxide, without the development of hypermagnesemia. In our experience, this therapy caused intolerable GI side effects and failed to reduce aluminum intake in most patients. PATIENTS AND METHODS We prospectively studied seven patients with end-stage renal disease treated with CAPD. Their average age was 44 years (range 26 to 68 years); six patients were male, and one was female. The patients had initiated CAPD with coventional peritoneal dialysate conIaining 1.5 mEq/L magnesium (Dianeal; Baxter Travenol, Deerfield, Ill) and were prescribed aluminum-containing phosphate binders (Basaljel [Wyeth, Philadelphia, Pal, Alucaps [Riker, Northridge, Calif], or Dialume [Armour Pharmaceutical Co, Tarrytown, NY]). The duration of CAPD prior to the study was 26 months (range 5 to 42 months). None had symptoms or laboratory findings of osteomalacia or dementia. Informed consent was obtained in all patients. The study was conducted in three phases. In the first phase, patients remained on their usual dialysis regimen and completed a 1- to 3-month baseline evaluation. In the second phase, patients were instructed to begin using peritoneal dialysate containing 0.5 mEq/L magnesium (PD2; Baxter 1favenol, Deerfield, TIl). They also were instructed to substitute an antacid containing magnesium hydroxide for part of their phosphatebinder dose. We initially recommended Maalox II (Rorer, Fort Washington, Pa), containing 166.8 mg magnesium and 248 mg aluminum per tablet, because of its high magnesium content and high potency as a phosphate binder. 12 During the next 1 to 3 months, the dose of Maalox II was increased, the dose of aluminum hydroxide was decreased, and the serum phosphorus
American Journal of Kidney Diseases. Vol VIII, No 3 (September). 1986: pp 192-195
MAGNESIUM HYDROXIDE AS PHOSPHATE BINDER
193
level was maintained within normal limits. The dose of Maalox II was increased until other aluminum hydroxide preparations had been discontinued, until the patient developed GI intolerance (diarrhea), or until the serum magnesium level rose to 3.5 mEq/L or higher. rNe chose this value for serum magnesium because previous studies have not shown toxicity in patients on dialysis with levels below this value. 8) In the third phase, patients were followed for an additional 1 to 3 months. If side effects from magnesium hydroxide had occurred in the second phase, the dose of Maalox II was decreased until side effects were tolerable and the aluminum hydroxide dose was increased in order to maintain a normal serum phosphorus level. In all three phases, patients were seen at 2- to 6-week intervals. The intake of phosphate binders, symptoms of hypomagnesemia or hypermagnesemia, bowel habits, and serum magnesium, phosphorus, and calcium levels were monitored at each visit. Phosphorus intake was assessed by dietary recall at the beginning and end of the study. Results obtained during all three phases were compared. Serum aluminum was measured in all patients during the baseline evaluation using a PerkinElmer 5000 rNaitham, Mass) atomic absorption spectrophotometer with a graphite furnace. Normal values for similar techniques are up to 7 /Lg/L6.13; values for dialysis patients ingesting aluminum hydroxide usually are in the range from 30 to 300 /Lg/L.7.I3-1' Data are reported as the mean ± SD. Comparisons were made by the paired t test. A value for P < .05 was considered significant.
Aluminum Dose (g/d)
1 2 3 4 5 6 7
3.63 3.83 4.15 4.15 3.11 1.27 1.90 3.15 ± 1.14
Mean ± SD
GI
Symptoms N N N N C C N
~
••
.It.
•
Control
Peak Mg dose
Tolerable Mg dose
3
•
m..J 2
:::!EE :::!E :::>
a: w
rr.
0
B 7
00
•
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0 a: 0
6
:z::
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O-a
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•
5
0..0-
:::!E :::>
E
• •
••
4 3 Peak Mg dose
Tolerable Mg dose
Fig 1. Serum magnesium and phosphorus levels. (A) The serum magnesium level during the three phases of the study (see text). (B) The serum phosphorus levels during the same phases. Black circles indicate values for individual patients. Means are indicated by a short line. Normal values are indicated by the shaded area.
Aluminum Dose, Magnesium Dose, and GI Symptoms
Phase 1: Aluminum Hydroxide Alone Patient No.
u; z
w
00
The serum aluminum levels were elevated in all patients at the onset of the study (185 ± 166 p.g/L; range 50 to 495 p.g/L). Table 1 and Fig 1 show the serum magnesium and phosphorus levels, dose of aluminum and magnesium, and GI symptoms for the seven patients during conventional therapy, during treatment with low magnesium dialysate and magnesium hydroxide at the peak dose, and at a dose tolerable to the patients. The serum magnesium concentration, serum phosphorus concentration, and aluminum dose did not differ significantly in these patients during treatment with the
•
4 :::!E :::>
a: w
RESULTS
Table 1.
A
Phase 2: Peak Dose Magnesium Hydroxide Aluminum Dose (gJd)
Magnesium Dose (gJd)
3.10 2.47 3.18 4.37 3.18 1.68 2.42 2.91 ± 0.84
1.00 0.17 1.50 1.00 1.50 1.17 1.33 1.10 ± 0.46
Abbreviations: D, diarrhea; C, constipation; N, none.
Phase 3: Tolerable Dose Magnesium Hydroxide GI
Symptoms D D D D D N D
Aluminum Dose (gJd)
Magnesium Dose (gJd)
3.10 0 3.83 0 2.33 1.00 3.74 0.50 3.50 1.00 1.68 1.17 2.28 1.00 2.92 ± 0.83 0.67 ± 0.50
GI
Symptoms N N N N N N N
194
JENNINGS ET AL
three regimens (P > .2). Serum calcium levels and dietary phosphorus intake also remained unchanged during the study (results not shown). Thus, there was no overall benefit of the low magnesium dialysate with magnesium-containing phosphate binders in reducing the mean aluminum dosage. There were no apparent side effects of the low magnesium dialysate. None of the patients developed hypomagnesemia. However, six of the seven patients had side effects from magnesium hydroxide. The dose of magnesium-containing phosphate binders was limited by diarrhea in six patients. The maximum tolerable dose of magnesium was 1.17 g/d. One patient (no. 1) developed diarrhea and symptomatic hypermagnesemia (Mg concentration 4.0 mEq/L) , manifested by muscle weakness, absent deep tendon reflexes, and slurred speech. These symptoms disappeared when magnesium hydroxide was discontinued. Attempts to reinstitute magnesium hydroxide in a lower dose resulted in recurrent diarrhea and mild asymptomatic hypermagnesemia. Eventually, magnesium hydroxide had to be discontinued altogether. One other patient (no. 2) also was unable to tolerate even small doses of magnesium-containing antacids, because of diarrhea. The dose of aluminum decreased substantially in only one patient (no. 3). However, the aluminum intake remained high. In the remaining four patients, aluminum dosage either decreased slightly (no. 4) or increased slightly (nos. 5, 6, and 7). In the five patients able to tolerate magnesium hydroxide, the dose of magnesium was 0.93 ± 0.25 g/d. The aluminum dose in these five patients was 2.92 ± 1.31 gld prior to beginning magnesium hydroxide and 2.71 ± 0.88 gld while taking magnesium hydroxide (P > .2). DISCUSSION
The widespread recognition of the toxicity of aluminum had led to a search for means of reducing the intake of aluminum contained in phosphate binders. Guillot et al suggested magnesium hydroxide might be safely used as a phosphate binder in hemodialysis patients. 8 Others, however, have warned of the potential risks of this therapy and advised against it. 9, 10 The safety and effectiveness of magnesium hydroxide as a phosphate binder in CAPD patients has not been studied.
In order to reduce the dose of aluminum hydroxide in CAPD patients, we prescribed phosphate binders with a mixture of aluminum and magnesium hydroxide and used a dialysate with a low magnesium concentration. In six of seven patients, the dose of magnesium hydroxide was limited by GI side effects. One patient also developed symptomatic hypermagnesemia. Two patients were unable to tolerate any magnesium hydroxide because of diarrhea. Five patients were able to tolerate small doses of magnesium hydroxide (0.5 to 1.17 g/d) , but in only one patient did the aluminum dose decrease greatly. In this patient, however, the dose of aluminum remained 2.33 gld, a dose that is associated with high serum aluminum levels in CAPD patients. 7 In our study, as in the study by Guillot et al, 8 the maximal tolerable dose of magnesium was approximately 1 g/d. Higher doses led to diarrhea and hypermagnesemia. In our study, the magnesium dose exceeded 1 gld in only one patient, and in ths patient, other aluminum hydroxide preparations could be eliminated. Nonetheless, the aluminum dose in this patient was not decreased. One explanation for this failure to reduce aluminum intake might be that the combination of magnesium and aluminum hydroxide is not as potent a phosphate binder as is aluminum hydroxide alone. Thus, in our experience, the combination of low magnesium peritoneal dialysate and phosphate binders containing both magnesium and aluminum hydroxide is not useful in decreasing the aluminum dosage in most patients on CAPD. Only a small subset of patients (one in seven in our experience) are able to reduce aluminum intake significantly. Most patients, however, develop GI symptoms and are able to tolerate only small doses of magnesium hydroxide or none at all. Furthermore, there is a moderate risk of symptomatic hypermagnesemia. Totally eliminating magnesium from dialysate might reduce the risk of hypermagnesemia, but it is highly unlikely that this would improve GI tolerance. We conclude that magnesium-containing phosphate binders will not achieve the goal of reducing intake of aluminum in most patients. Recently, some investigators used calcium carbonate as the sole phosphate binder in order to avoid aluminum toxicity.5,16 Further clinical studies are indicated to discover potent and tolerable alternatives to aluminum hydroxide for patients on dialysis.
195
MAGNESIUM HYDROXIDE AS PHOSPHATE BINDER
ADDENDUM A recent study demonstrated the feasibility of substituting magnesium carbonate for aluminum hydroxide as a phosphate binder in patients treated by hemodialysis and a magnesium-free dialysate. 17 The dose of magnesium was 0.16 to 0.5 g/d and maintained the mean serum phosphorus at 5.5 to 6.0 mg/dL for 2 years. Aluminum hydroxide was discontinued and serum aluminum levels declined. The efficacy of lower doses of magnesium in this study may be related to differences in the phos-
phate-binding capacity of magnesium carbonate and magnesium hydroxide or to differences in intake and removal of phosphorus in patients treated by hemodialysis and CAPD.
ACKNOWLEDGMENTS We wish to thank Travenol Laboratories for providing custom-made PD2 solutions, Dr Clive Bach for assisting in the study, Andrew MacAulay and Joyce Ellis, Clinical Study Unit at New England Medical Center, for measuring aluminum (supported by GCRC Grant No. RR 00(54), and Drs Nicolaos E. Madias and John T. Harrington for reading the manuscript.
REFERENCES 1. Wills MR, Savory J: Aluminum poisoning: Dialysis encephalopathy, osteomalacia and anaemia. Lancet 2:29-33, 1983 2. Boyce BF, Fell GS, Elder HY, et al: Hypercalcemic osteomalacia due to aluminum toxicity. Lancet 2:1009-1013, 1982 3. Arieff AI, Cooper JD, Armstrong D, et al: Dementia, renal failure and brain aluminum. Ann Intern Med 90:741747, 1979 4. Committee of the European Dialysis and Transplant Association: Dialysis dementia in Europe. Lancet 2:190-192, 1980 5. Andreoli Sp, Bergstein JM, Sherrard OJ: Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 310:1079-1084, 1984 6. Kaehny WD, Hegg Ap, Alfrey AC: Gastrointestinal absorption of aluminum from aluminum containing antacids. N Engl J Med 296:1389-1390, 1977 7. Rottembourg J, Gallego JL, Jaudon MC, et al: Serum concentration and peritoneal transfer of aluminum during treatment by continuous ambulatory peritoneal dialysis. Kidney Int 25:919-924, 1984 8. Guillot Ap, Hood VL, Runge CF, et al: The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron 30:114117, 1982 9. Brunner FP, Thiel G: Re: The use of magnesium-contain-
ing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron 32:266, 1982 10. Randall RE, Cohen MD, Spray CC, et al: Hypermagnesemia in renal failure. Etiology and toxic manifestations. Ann Intern Med 61:73-88, 1964 11. Alfrey AC,Miller NL: Bone magnesium pools in uremia. J Clin Invest 52:3019-3027, 1973 12. Bailey GL, Vona JP: Pharmacodynamics in renal failure, in Bailey GL (ed): Hemodialysis: Principles and Practice. Orlando, Fla, Academic, 1972, pp 117-186 13. Oster 0: The aluminum content of human serum determined by atomic absorption spectroscopy with a graphite furnace. Clin Chern Acta 114:53-60, 1981 14. Fleming LW, Stewart WK, Fell GS, et al: The effect of oral aluminum therapy on plasma aluminum levels in patients with chronic renal failure in an area with low water aluminum. Clin Nephrol 17:222-227, 1982 15. Milliner DS, Nebeker HG, Ott SM, et al: Use of the deferoxamine test in the diagnosis of aluminum-related osteodystrophy. Ann Intern Med 101:775-780, 1984 16. Slatopolsky E, Weerts C, Lopez S, et al: Calcium carbonate is an effective phosphorus-binder in dialysis patients. Kidney Int 27:173, 1985 (abstr) 17. O'Donovan RO, Baldwin D, Hammer M, et al: Substitution of aluminum salts by magnesium salts in control of dialysis hyperphosphatemia. Lancet 1:880-882, 1986