Original Article
Aluminum Accumulation during Treatment with Aluminum Hydroxide and Dialysis in Children and Young Adults with Chronic Renal Disease
N Engl J Med 1991; 324:527-531February 21, 1991
- Abstract
- Abstract
Background.
The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated.
Methods.
Seventeen children and young adults (mean [±SD] age, 14.1 ±3.7 years) undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to serum phosphorus levels). Aluminum retention was assessed by serial measurements of plasma aluminum, deferoxamine-infusion tests, and measurements of bone aluminum content during a mean (±SD) follow-up of 13±2 months. The evolution of bone disease was also evaluated.
Results.
Plasma aluminum levels and the increment in plasma aluminum after infusion of deferoxamine increased from base-line values in the patients treated with aluminum hydroxide, and aluminum-related bone disease developed in one patient. Serum phosphorus levels remained higher and serum calcium levels lower in the patients receiving aluminum hydroxide than in those receiving calcium carbonate. The skeletal lesions of secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide (P<0.025).
Conclusions.
Aluminum hydroxide is less effective than calcium carbonate as a phosphate-binding agent for the control of hyperphosphatemia and is associated with aluminum retention in children and young adults with chronic renal failure who are receiving dialysis therapy. (N Engl J Med 1991; 324:527–31.)
Media in This Article
Figure 1
Mean (±SE) Serum Calcium (Upper Panel) and Phosphorus (Lower Panel) Concentrations in 17 Children and Young Adults with Chronic Renal Insufficiency Treated with Dialysis and Aluminum Hydroxide (N = 7; Open Circles) or Calcium Carbonate (N = 10; Closed Circles).Figure 2
Mean (±SE) Basal Plasma Aluminum Concentrations in 17 Children and Young Adults with Chronic Renal Insufficiency Treated with Dialysis and Aluminum Hydroxide (N = 7; Open Bars) or Calcium Carbonate (N = 10; Hatched Bars).Article Activity
- Article
THE control of hyperphosphatemia is a difficult clinical problem in the care of patients with chronic renal failure who are undergoing regular dialysis.1 With the recognition that long-term ingestion of large doses of phosphate-binding antacids containing aluminum can result in aluminum retention and toxicity, 2 3 4 the use of phosphate-binding agents free of this element, such as calcium carbonate, has been recommended for patients with chronic renal failure.5 6 7 Unfortunately, hypercalcemia or hyperphosphatemia occurs in 25 to 50 percent of patients receiving large oral doses of calcium carbonate.6 7 8 It is often necessary, therefore, to administer small amounts of aluminum hydroxide with calcium carbonate to achieve adequate control of serum phosphorus levels without the development of hypercalcemia.7 , 8 Consequently, medications containing aluminum are still given to many patients with chronic renal failure.
The maximal recommended doses of aluminum hydroxide in patients undergoing regular dialysis are 30 mg per kilogram of body weight per day in children and 40 to 45 mg per kilogram per day in adults.9 These amounts have been established as limiting the potential for aluminum toxicity, but the safety and efficacy of such doses have not been evaluated. This prospective, randomized trial was undertaken to determine the degree of aluminum loading that occurs with the recommended doses of aluminum hydroxide in children and young adults undergoing peritoneal dialysis; the results were compared with those in patients treated with calcium carbonate as the sole phosphate-binding agent. The retention of aluminum in tissues was assessed by serial measurements of plasma aluminum levels, deferoxamine-infusion tests, and measurements of the aluminum content of bone, and the evolution of renal osteodystrophy was evaluated by bone biopsy.
Methods
All patients between the ages of 3 and 21 years who were undergoing long-term peritoneal dialysis at the UCLA Medical Center were considered for this study, which was planned to last one year; the sole exclusion criterion was evidence on bone biopsy of aluminum-related bone disease as defined previously by us.10 The patients entering the study were randomly assigned to receive aluminum hydroxide or calcium carbonate as the sole phosphate-binding agent. The study protocol was approved by the UCLA Human Subjects Protection Committee, and informed consent was obtained from all patients or their parents.
A total of 22 patients entered the study: 12 were assigned to treatment with oral calcium carbonate and 10 to treatment with oral aluminum hydroxide. Five patients were withdrawn because they underwent renal transplantation. Thus, a total of 17 patients completed the study; 10 were treated with calcium carbonate and 7 with aluminum hydroxide. The primary renal disease and Z scores for height are shown in Table 1Table 1
Characteristics of the Children and Young Adults with Chronic Renal Insufficiency Who Were Treated with Dialysis and Calcium Carbonate or Aluminum Hydroxide.; the Z scores represent the number of standard deviations from normal age-adjusted and sex-adjusted values for height and were determined before and at the end of the study. The patients underwent peritoneal dialysis with standard peritoneal dialysate (Dianeal, Baxter, Deerfield, Ill.) containing 1.75 mmol of calcium per liter, and the amount of dextrose in the dialysate was adjusted to achieve fluid balance, according to the requirements of the individual patient. The patients had been treated by dialysis for an average (±SD) of 17±12 months before entering the study. The mean duration of treatment before the second bone biopsy was 13±2 months.Before the study, all patients had received daily oral doses of calcitriol and either aluminum hydroxide or calcium carbonate. Oral calcitriol was continued throughout the study, and the doses were adjusted in individual patients on the basis of frequent measurements of serum calcium and phosphorus.6 , 11 The daily doses of calcitriol were changed in increments of 0.25 μg at monthly intervals to maintain total serum calcium levels between 2.6 and 2.8 mmol per liter if serum phosphorus levels remained at or below 1.9 mmol per liter.11 Hypercalcemia was defined as a serum calcium concentration equal to or greater than 2.8 mmol per liter, and hyperphosphatemia was defined as a serum phosphorus level above 1.9 mmol per liter.
In patients given calcium carbonate, the daily dose ranged from 2.5 to 12 g; it was adjusted on the basis of changes in serum phosphorus concentrations. The dose of aluminum hydroxide was also adjusted according to serum phosphorus levels, but the maximal daily dose was limited to 30 mg per kilogram as recommended by Sedman et al. for children with renal failure.3 Each phosphate-binding agent was given as tablets in divided doses with meals, 12 and none of the patients received citrate or buffered citric acid solutions.
Dietary intake was estimated by diet interviews, three-day diet diaries, and weighing of food for three days before each clinic visit as previously described.13 The results are presented as cumulative mean values for calcium and phosphate intake during the study period. Adequate dietary histories were available for 6 of the 7 patients who received aluminum hydroxide and for 8 of the 10 patients who received calcium carbonate. Growth was assessed by changes in the Z score for height after adjustment for chronologic age and sex, according to guidelines established for children with chronic renal failure.14
Biopsies of the iliac crest were performed after double tetracycline labeling. Quantitative histomorphometric analysis of bone was completed in all patients before and at the end of the study as previously described.10 Separate samples of cancellous bone were also obtained for measurements of the aluminum content of bone. Sections of undecalcified bone were stained by a modification of the Goldner technique for quantitative assessment by light microscopy. Unstained sections of bone were mounted in 10 percent glycerol and viewed under epifluorescent illumination for measurements of the tetracycline labels10; the amount of surface-stainable aluminum in bone was determined in sections stained by the aurine tricarboxylic acid method.10 , 15
Deferoxamine-infusion tests were performed at the start and at the end of the study with an intravenous dose of 40 mg per kilogram; plasma aluminum levels were measured before and 24 hours after the infusion.16 Samples of blood were obtained every three months for determinations of serum parathyroid hormone levels and every four months for measurements of plasma aluminum. Serum calcium, phosphorus, alkaline phosphatase, and albumin levels were measured at monthly intervals.10
Plasma aluminum levels and the content of aluminum in bone were measured by flameless atomic absorption spectrometry, 17 and serum calcium (normal range, 2.1 to 2.5 mmol per liter), phosphorus (normal range, 0.8 to 1.3 mmol per liter), alkaline phosphatase (normal range, 30 to 105 U per liter), and albumin concentrations were measured with a Technicon AutoAnalyzer II (Tarrytown, N.Y.). Serum levels of immunoreactive parathyroid hormone were determined with a radioimmunoassay that reacts with the midcarboxy-terminal region of the parathyroid hormone molecule (normal range, <3 to 10 ml-eq per liter).18
All results are expressed as means ±SE. Statistical analysis of the data was done with analysis of variance with contrasts and the two-tailed t-test for paired and unpaired samples.19 The rank-sum test and the sign test were used to assess results that were not normally distributed.19 Changes in the distribution of histologic lesions of bone during the study were evaluated by chi-square anal ysis.19
Results
Serum Biochemical Determinations
The mean serum calcium levels did not differ between the groups at the start of the study but had increased after three months and remained elevated in the patients treated with calcium carbonate (Fig. 1Figure 1
Mean (±SE) Serum Calcium (Upper Panel) and Phosphorus (Lower Panel) Concentrations in 17 Children and Young Adults with Chronic Renal Insufficiency Treated with Dialysis and Aluminum Hydroxide (N = 7; Open Circles) or Calcium Carbonate (N = 10; Closed Circles).). In contrast, the mean serum calcium concentrations did not change substantially from base-line values in the patients treated with aluminum hydroxide, except during the seventh month of the study (Fig. 1). There were no changes in serum albumin levels during the study in either group (Table 2Table 2
Serum Biochemical Values and Doses of Oral Calcitriol in Children and Young Adults with Chronic Renal Insufficiency Who Received Calcium Carbonate or Aluminum Hydroxide.*). The mean dietary calcium intake was 610±89 mg per day in the patients treated with aluminum hydroxide and 818± 120 mg per day in those treated with calcium carbonate; these values correspond to 50±7 percent and 71 ±10 percent, respectively, of the recommended daily allowance for calcium in children.The mean serum phosphorus concentrations were higher initially in the patients treated with aluminum hydroxide: 2.1 ±0.3 mmol per liter, as compared with 1.9±0.4 mmol per liter (P<0.01) in those treated with calcium carbonate. This difference persisted throughout the study (Fig. 1). The initial values represent single determinations obtained at the time of the first bone biopsy. However, when base-line values for serum phosphorus were expressed as the average of three consecutive monthly determinations made immediately before the study, the mean value in the patients receiving aluminum hydroxide was similar to that in the patients receiving calcium carbonate (2.0±0.1 vs. 1.9±0.2 mmol per liter). Overt hyperphosphatemia, defined as a serum phosphorus level of more than 1.9 mmol per liter, was more common in the patients treated with aluminum hydroxide, despite their having a moderately lower dietary intake of phosphorus than those receiving calcium carbonate (761 ±66 vs. 985±133 mg per day). These values correspond to 66±6 percent and 92±10 percent, respectively, of the recommended daily allowance for phosphorus in each group.
The mean serum level of alkaline phosphatase was initially higher in the patients treated with calcium carbonate, and the value did not change significantly during treatment (Table 2). In contrast, the mean serum level of alkaline phosphatase increased in the patients treated with aluminum hydroxide; thus, the values in the two groups were similar at the end of the study. There were negligible differences between the groups in the initial serum levels of parathyroid hormone, but the levels increased significantly in the patients treated with aluminum hydroxide (Table 2). In contrast, serum parathyroid hormone levels did not change significantly in the patients receiving calcium carbonate.
Neither the average nor the maximal dose of calcitriol administered during the study differed significantly in the two groups (Table 2). There were six episodes of hypercalcemia, defined as a serum calcium level ≥2.8 mmol per liter, in six patients treated with calcium carbonate; hypercalcemia developed on three occasions in two patients receiving aluminum hydroxide. The peak serum calcium level during the episodes of hypercalcemia was greater in the patients treated with calcium carbonate than in those treated with aluminum hydroxide (3.3±0.1 vs. 2.9±0.1 mmol per liter, P<0.01).
Histologic Examination of Bone
On initial examination, the distribution of histologic lesions of renal osteodystrophy did not differ in the two groups of patients. The bone biopsy provided evidence of secondary hyperparathyroidism in 7 of the 10 patients treated with calcium carbonate and in 4 of the 7 treated with aluminum hydroxide, in the form of tissue fibrosis, increased rates of bone formation, or both. On follow-up biopsy, 7 of the 10 patients treated with calcium carbonate had normal histologic features and rates of bone formation. In contrast, renal osteodystrophy persisted or progressed in six of the seven patients treated with aluminum hydroxide (chi-square = 5.13, P<0.025). In these patients, the rate of bone formation either did not decrease or it increased further during treatment, and the severity of tissue fibrosis either did not change or increased. Moreover, one patient who initially had an aplastic lesion of bone with no surface-stainable aluminum was subsequently found to have a mixed lesion of renal osteodystrophy, characterized by marked marrow fibrosis, increases in total osteoid area, and thickened osteoid seams — changes indicative of osteomalacia — and surface-stainable aluminum on 24 percent of the perimeter of trabecular bone.
Assessment of Aluminum Retention in Tissues
The mean basal plasma aluminum level and the increment observed after single infusions of deferoxamine did not differ significantly between the groups at the start of the study (Fig. 2Figure 2
Mean (±SE) Basal Plasma Aluminum Concentrations in 17 Children and Young Adults with Chronic Renal Insufficiency Treated with Dialysis and Aluminum Hydroxide (N = 7; Open Bars) or Calcium Carbonate (N = 10; Hatched Bars). and 3Figure 3
Mean (±SE) Increments in Plasma Aluminum Concentrations after Single Intravenous Infusions of Deferoxamine (40 mg per Kilogram) before and after Treatment with Aluminum Hydroxide (N = 7; Open Bars) or Calcium Carbonate (N = 10; Hatched Bars) in Children and Young Adults with Chronic Renal Insufficiency Treated with Dialysis.). The basal plasma aluminum levels increased progressively, however, in the patients receiving aluminum hydroxide, whereas the levels decreased in those receiving calcium carbonate (Fig. 2). The increment in plasma aluminum after the infusion of deferoxamine was greater at the end of the study in patients treated with aluminum hydroxide than in those treated with calcium carbonate (Fig- 3).The aluminum content of bone did not differ between the groups either before or at the end of the study. The initial values were 10±5 and 10±7 mg per kilogram of dry weight of bone, respectively, in the patients receiving calcium carbonate and those receiving aluminum hydroxide, and the corresponding values were 9±3 and 10±5 mg per kilogram of dry weight at the end of the study. Surface-stainable aluminum was present on 26 percent of trabecular-bone surfaces on initial biopsy in one patient with osteitis fibrosa who received calcium carbonate; after 12 months, no aluminum was seen. In contrast, one patient treated with aluminum hydroxide had stainable aluminum on 24 percent of trabecular-bone surfaces at the end of the study and histologic features consistent with diminished bone formation. No other patients had stainable aluminum on bone surfaces.
Discussion
These results indicate that the retention of aluminum in tissues is evident after approximately one year of treatment with currently recommended doses of aluminum hydroxide in children and young adults undergoing long-term peritoneal dialysis. The basal plasma aluminum levels increased progressively in the patients treated with aluminum hydroxide, and the increment in plasma aluminum after single infusions of deferoxamine was also greater at the end of the study in the patients treated with aluminum hydroxide than in those treated with calcium carbonate. Although the aluminum content of bone, measured by flameless atomic absorption spectrometry, did not increase in the group receiving aluminum hydroxide, one of seven patients had histologic evidence of aluminum deposition in bone; this patient also had other histomorphometric features of aluminum toxicity to bone. Such findings indicate that the use of even limited amounts of aluminum hydroxide in young patients undergoing regular peritoneal dialysis is associated with a measurable risk of aluminum accumulation and tissue toxicity.20
The results do not differ substantially from those reported by Jenkins et al. in adult patients undergoing long-term hemodialysis.21 Although these authors suggested that there was only limited evidence of aluminum toxicity in their patients, who received an average daily dose of 2.6 g of aluminum hydroxide for a mean of 49 months, 1 of the 16 patients had evidence of aluminum-related bone disease. Aluminum levels in bone exceeded 50 mg per kilogram of dry weight in three other patients, and plasma aluminum levels were elevated substantially in all patients.21 Thus, our findings and those of Jenkins et al.21 indicate that aluminum is retained in the body both in adults and in children undergoing regular dialysis while receiving oral aluminum hydroxide therapy. On the basis of the considerably shorter duration of our study, the length of treatment required to produce aluminum retention in tissues may be shorter in younger patients.
In addition to the greater degree of aluminum loading, the patients who were treated with aluminum hydroxide had persistent hyperphosphatemia, despite a somewhat lower level of dietary phosphorus intake. Such findings indicate that the use of aluminum hydroxide in doses that have been recommended to limit the risk of aluminum loading in young patients undergoing regular peritoneal dialysis is insufficient to control serum phosphorus levels adequately.
Poor compliance with the medication regimen is unlikely to account for the differences between the patients treated with aluminum hydroxide and those treated with calcium carbonate. The increase in plasma aluminum levels during treatment with aluminum hydroxide supports the contention that the patients ingested substantial amounts of aluminum hydroxide during the study. Previous studies in children undergoing long-term peritoneal dialysis have demonstrated that large oral doses of aluminum hydroxide can effectively control serum phosphorus levels but that serum aluminum levels correlate with the amount of aluminum hydroxide ingested each day.4
The importance of this observation is underscored by the high rate of progression of secondary hyperparathyroidism in the patients treated with aluminum hydroxide. Six of the seven patients had progressive histologic changes of secondary hyperparathyroidism despite treatment with oral calcitriol. In contrast, the patients treated with calcium carbonate had better control of serum phosphorus levels, higher serum calcium levels, and a more favorable histologic response to oral calcitriol therapy. Also, several biochemical indexes of secondary hyperparathyroidism worsened in the patients receiving aluminum hydroxide; serum levels of parathyroid hormone and alkaline phosphatase increased, whereas they did not change or decreased in the patients treated with calcium carbonate.
Overall, the results suggest that calcium carbonate is more effective than aluminum hydroxide when used as the primary phosphate-binding agent during oral calcitriol therapy in patients with secondary hyperparathyroidism who are undergoing dialysis. This difference is probably related in part to the maintenance of higher serum calcium levels. There were no differences between the groups in either the average daily dose or in maximal daily dose of oral calcitriol during the study. Gokal et al. reported similar findings during treatment with 1 α-hydroxycholecalciferol in adult patients undergoing long-term peritoneal dialysis.22
The results also suggest that aluminum hydroxide should not be used as a primary phosphate-binding agent in children and young adults with chronic renal failure because the risk of aluminum toxicity is substantial. Although lower doses of aluminum hydroxide have been recommended for children than for adults in an effort to reduce the potential for aluminum toxicity, these are not adequate to control serum phosphorus levels in children.
Recent observations indicate that hypercalcemia can be more effectively prevented in patients undergoing dialysis who are ingesting large daily doses of calcium carbonate by the use of dialysis solutions that contain lower concentrations of calcium.23 , 24 In addition, calcium acetate has been shown to be a more potent phosphate-binding agent than calcium carbonate.25 Although the long-term safety and efficacy of these two therapeutic options have yet to be determined, they provide alternatives to aluminum-containing medications for the management of phosphate retention in patients with chronic renal failure.
From the Departments of Pediatrics (I.B.S., J.F., P.N.) and Medicine (W.G.G.), UCLA School of Medicine, Los Angeles, and the Medical and Research Services, Sepulveda Veterans Affairs Medical Center, Sepulveda, Calif. (W.G.G.). Address reprint requests to Dr. Salusky at the Department of Pediatrics, UCLA Center for the Health Sciences, A2–331 MDCC, Los Angeles, CA 90024–1752.
Supported in part by grants (DK-35423, AR-35470, and RR-00865) from the U.S. Public Health Service and research funds from the Department of Veterans Affairs.
Portions of this work were presented at the 22nd annual meeting of the American Society of Nephrology, Washington, DC, December 3–7, 1989.
We are indebted to Ms. Jeanenne O'Connor for valuable technical assistance in the processing of bone-biopsy specimens; to Dr. J.W. Coburn of the Nephrology Section, Veterans Affairs Medical Center, West Los Angeles, Wadsworth Division, and Mr. W. Van Buren for measurements of aluminum levels in plasma and bone; to Dr. Eduardo Slatopolsky of the Renal Division, Washington University School of Medicine, St. Louis, for measurements of serum parathyroid hormone; and to Mrs. Lisa Newman for assistance in the preparation of the manuscript.
- References
References
1
Cobum
Full Text | Web of Science | Medline2
Andreoli
Full Text | Web of Science | Medline3
Sedman
CrossRef | Web of Science | Medline4
Salusky
CrossRef | Web of Science | Medline5
Moriniere
Medline6
Salusky
CrossRef | Web of Science | Medline7
Slatopolsky
Full Text | Web of Science | Medline8
Foumier
Medline9
Winney
Medline10
Salusky
CrossRef | Web of Science | Medline11
Salusky
CrossRef | Web of Science | Medline12
Schiller
Full Text | Web of Science | Medline13
Salusky 14
Preece MA. Methodological problems in the assessment of growth and interpretation of growth changes in children with renal disease. In: Scharer K, ed. Pediatric and adolescent endocrinology. Vol. 20. Basel, Switzerland: Karger, 1989:4–14.
15
Maloney
Medline16
Hercz
CrossRef | Web of Science | Medline17
LeGendre
Web of Science | Medline18
Hruska
CrossRef | Web of Science | Medline19
Dixon WJ, Massey FJ Jr. Introduction to statistical analysis. 4th ed. New York: McGraw-Hill, 1983.
20
Froment
CrossRef | Web of Science | Medline21
Jenkins
Web of Science | Medline22
Gokal
CrossRef | Web of Science | Medline23
Mactier
Web of Science | Medline24
Slatopolsky
CrossRef | Web of Science | Medline25
Mai
CrossRef | Web of Science | Medline
- Citing Articles (43)
Citing Articles
1
Katherine Wesseling Perry, Isidro B. Salusky. 2012. Chronic Kidney Disease Mineral and Bone Disorder. , 795-820.
CrossRef2
NICHOLAS A GRAY, RATHIKA KRISHNASAMY, DEEPAK L VARDESH, PETER R HOLLETT, CHRIS M ANSTEY. (2011) Impact of non-traditional phosphate binders and cinacalcet on haemodialysis patient biochemistry, pill burden and cost. Nephrology 16:8, 688-696
CrossRef3
Denis F Geary, Elisabeth M Hodson, Jonathan C Craig. (2011) Cochrane review: Interventions for bone disease in children with chronic kidney disease. Evidence-Based Child Health: A Cochrane Review Journal 6:2, 298-383
CrossRef4
Donald A. Molony, Brett W. Stephens. (2011) Derangements in Phosphate Metabolism in Chronic Kidney Diseases/Endstage Renal Disease: Therapeutic Considerations. Advances in Chronic Kidney Disease 18:2, 120-131
CrossRef5
Sankar D Navaneethan, Suetonia C Palmer, Mariacristina Vecchio, Jonathan C Craig, Grahame J Elder, Giovanni FM Strippoli, Sankar D Navaneethan. 2011. Phosphate binders for preventing and treating bone disease in chronic kidney disease patients. .
CrossRef6
Katherine Wesseling-Perry, Renata C Pereira, Shobha Sahney, Barbara Gales, He-Jing Wang, Robert Elashoff, Harald Jüppner, Isidro B Salusky. (2011) Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism. Kidney International 79:1, 112-119
CrossRef7
Tonelli, Marcello, Pannu, Neesh, Manns, Braden, . (2010) Oral Phosphate Binders in Patients with Kidney Failure. New England Journal of Medicine 362:14, 1312-1324
Full Text8
Denis F Geary, Elisabeth M Hodson, Jonathan C Craig, Denis F Geary. 2010. Interventions for bone disease in children with chronic kidney disease. .
CrossRef9
Koji Takei, Sian Dale, Heather Charles, Akira Sasaki, Shigekazu Nakajima. (2010) Absorption and Excretion of Colestilan in Healthy Subjects. Clinical Pharmacokinetics 49:1, 47-52
CrossRef10
Anca Gal-Moscovici, Stuart M. Sprague, Edgar V. Lerma. (2007) Treatment of renal osteodystrophy. Clinical Reviews in Bone and Mineral Metabolism 5:1, 27-38
CrossRef11
David N. S. Kerr, Michael K. Ward, Hewett A. Ellis, William Simpson, Ian S. Parkinson. 2007. Aluminium Intoxication in Renal Disease. , 123-141.
CrossRef12
Keith A. Hruska, Georges Saab, Suresh Mathew, Richard Lund. (2007) PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: Renal Osteodystrophy, Phosphate Homeostasis, and Vascular Calcification. Seminars in Dialysis 20:4, 309-315
CrossRef13
I B Salusky. (2006) A new era in phosphate binder therapy: What are the options?. Kidney International 70, S10-S15
CrossRef14
William G. Goodman. (2006) Renal osteodystrophy for nonnephrologists. Journal of Bone and Mineral Metabolism 24:2, 161-163
CrossRef15
Youichi Iwasaki, Hiroya Takami, Masahide Tani, Yoshiyuki Yamaguchi, Hiromichi Goto, Yoshikazu Goto, Yoshiaki Goto, Takashi Shigematsu. (2005) Efficacy of Combined Sevelamer and Calcium Carbonate Therapy for Hyperphosphatemia in Japanese Hemodialysis Patients. Therapeutic Apheresis and Dialysis 9:4, 347-351
CrossRef16
Donald A. Molony, Bhamidipati Murthy. (2005) Accumulation of Metals and Minerals from Phosphate Binders. Blood Purification 23:1, 2-11
CrossRef17
William G. Goodman. (2004) The Consequences of Uncontrolled Secondary Hyperparathyroidism and Its Treatment in Chronic Kidney Disease. Seminars in Dialysis 17:3, 209-216
CrossRef18
Yoram Nevo, Miriam Kutai, Joseph Jossiphov, Amir Livne, Zvi Neeman, Talmon Arad, Ronit Popovitz-Biro, Jacob Atsmon, Yehuda Shapira, Dov Soffer. (2004) Childhood macrophagic myofasciitis—consanguinity and clinicopathological features. Neuromuscular Disorders 14:4, 246-252
CrossRef19
William G. Goodman. (2003) New assays for parathyroid hormone (PTH) and the relevance of PTH fragments in renal failure. Kidney International 64:s87, 120-124
CrossRef20
Garabed Eknoyan, Adeera Levin, Nathan W Levin. (2003) Bone metabolism and disease in chronic kidney disease. American Journal of Kidney Diseases 42, 1-201
CrossRef21
William G Goodman, Harald Jüppner, Isidro B Salusky, Donald J Sherrard. (2003) Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy. Kidney International 63:1, 1-11
CrossRef22
Grahame J Elder. (2001) Pathogenesis and management of hyperparathyroidism in end-stage renal disease and after renal transplantation. Nephrology 6:4, 155-160
CrossRef23
Su-Hui Lee, Jenq-Wen Huang, Kuan-Yu Hung, Li-Jer Leu, Yao-Tung Kan, Chwei-Shiun Yang, Der Chung Wu, Chao-Lin Huang, Pei-Yuan Chen, Jui-San Chen, Wan-Yu Chen. (2000) Trace Metals' Abnormalities in Hemodialysis Patients: Relationship with Medications. Artificial Organs 24:11, 841-844
CrossRef24
Olafur S Indridason, L Darryl Quarles. (2000) Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Kidney International 57:1, 282-292
CrossRef25
Sandra Desroches, Fabrice Biron, Guy Berthon. (1999) Aluminum speciation studies in biological fluids Part 5. A quantitative investigation of Al(III) complex equilibria with desferrioxamine, 2,3-dihydroxybenzoic acid, Tiron, CP20 (L1), and CP94 under physiological conditions, and computer-aided assessment of the aluminum-mobilizing capacities of these ligands in vivo. Journal of Inorganic Biochemistry 75:1, 27-35
CrossRef26
Alok Kalia. (1999) Dialysis therapy in end-stage renal disease. The Indian Journal of Pediatrics 66:2, 255-262
CrossRef27
Isidro B Salusky, Beatriz D Kuizon, Thomas R Belin, Jorge A Ramirez, Barbara Gales, Gino V Segre, William G Goodman. (1998) Intermittent calcitriol therapy in secondary hyperparathyroidism: A comparison between oral and intraperitoneal administration. Kidney International 54:3, 907-914
CrossRef28
Didier A. Mandelbrot. (1998) Gastrointestinal Bleeding in Patients on Dialysis. Seminars in Dialysis 11:3, 161-166
CrossRef29
H. Brandenberger, M. Roth. 1997. 2.10 Metals of Toxicological Significance. , 285-344.
CrossRef30
Deepinder Julka, K. D. Gill. (1996) Effect of aluminum on regional brain antioxidant defense status in Wistar rats. Research in Experimental Medicine 196:1, 187-194
CrossRef31
Thomas H Ittel, Silvia Kinzel, Annette Ortmanns, Heinz-Günter Sieberth. (1996) Effect of iron status on the intestinal absorption of aluminum: A reappraisal. Kidney International 50:6, 1879-1888
CrossRef32
Isidro B. Salusky, William G. Goodman. (1996) The management of renal osteodystrophy. Pediatric Nephrology 10:5, 651-653
CrossRef33
David M. Kates, Dennis L. Andress. (1996) Control of Hyperphosphatemia in Renal Failure: Role of Aluminum. Seminars in Dialysis 9:4, 310-314
CrossRef34
James A. Delmez. (1995) Avoiding Renal Osteodystrophy in Peritoneal Dialysis Patients. Seminars in Dialysis 8:6, 373-377
CrossRef35
A. Wicklund Glynn, A. Sparen, L.-G. Danielsson, G. Haegglund, L. Jorhem. (1995) Bioavailability of labile aluminium in acidic drinking water: A study in the rat. Food and Chemical Toxicology 33:5, 403-408
CrossRef36
Jorge A. Ramirez, William G. Goodman, Isidro B. Salusky. (1994) Optimal Management of Renal Osteodystrophy in Children Treated with CAPD and CCPD. Seminars in Dialysis 7:6, 435-441
CrossRef37
William G Goodman, Jorge A Ramirez, Thomas R Belin, Yun Chon, Barbara Gales, Gino V Segre, Isidro B Salusky. (1994) Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney International 46:4, 1160-1166
CrossRef38
Giuseppe Cannella, Ermanno Bonucci, Davide Rolla, Paola Ballanti, Enzo Moriero, Roberta De Grandi, Carla Augeri, Franco Claudiani, Giovanni Di Maio. (1994) Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. Kidney International 46:4, 1124-1132
CrossRef39
Àngel Argilés, Peter G Kerr, Bernard Canaud, Jean Louis Flavier, Charles Mion. (1993) Calcium kinetics and the long-term effects of lowering dialysate calcium concentration. Kidney International 43:3, 630-640
CrossRef40
Arlen R. Severson, Craig F. Haut, Conrad E. Firling, Thomas E. Huntley. (1992) Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation. Archives of Toxicology 66:10, 706-712
CrossRef41
(1991) Aluminum Accumulation in Patients with Chronic Renal Disease. New England Journal of Medicine 325:3, 208-209
Full Text42
Richard A. Sherman. (1991) Briefly Noted. Seminars in Dialysis 4:3, 209-210
CrossRef43
Sherrard, Donald J., . (1991) Aluminum — Much Ado about Something. New England Journal of Medicine 324:8, 558-559
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