Effective Phosphate Binder Research Articles

Severe Hyperparathyroidism Despite Paricalcitol (Zemplar) Therapy: One Year Follow-up

Paricalcitol, a new Vit. D analogue is thought to be more potent than Calcitriol and has also been reported to cause less hypercalcemia. We report one-year follow-up on patients (N = 74) from one inner city dialysis unit. Patients were stratified in groups A, B, C, D depending on intact Paratharmone (iPTH) levels i.e., 600 respectively. Serum Ca, PO4, alkaline phosphatase (ALK), albumin (ALB), hemoglobin (Hb) was measured monthly and serum iPTH was checked quarterly. The results are as follows: Group # PTH Ca PO4 ZPR Hb EPO pg/dl mg/dl mg/dl mcg/hd g/dl U/kg/hd A 6 56.83* 9.74 5.32 0 11.72 255.8† B 22 197.01** 9.04 5.53 2.48¶ 12.12 137.55 C 29 422.89** 9.4 5.73 4.54¶¶ 11.86 128.87 D 17 1253.4** 9.88 7.21 12.51¶¶ 12.1 74.35†† PTH: p < 0.05 = *vs**, ZPR(zemplar): p < 0.05¶ vs¶¶, mcg: microgram EPO(erythropoietin): p < 0.05 = † vs††, Mean age, weight, URR, ALB., ALK. and iron indices were not statistically different in all groups. Mean duration of hemodialysis (HD) was 34, 30, 57 & 65 months in groups A, B, C, D respectively. None of these patients had symptomatic bone disease. Seven patients were changed to low Ca (1.0 meq/L) bath secondary to hypercalcemia (Ca > 11.5) & severe hyperparathyroidism (HPT). This data suggest that severe HPT is frequent despite aggressive Paricalcitol therapy in the inner city HD population. More effective noncalcium phosphate binders and/or calcimimetic agents may be needed in addition to dietary and medication compliance in group D to control severe HPT. Interestingly patients with low PTH (< 100) showed relative epogen resistance while patients in group D required smaller epogen doses. There was inverse relationship between ZPR & EPO dosage. The effect of ZPR on EPO responsiveness needs to be confirmed in larger study.

Critical appraisal of sevelamer for the treatment of hyperphosphatemia in patients with chronic renal failure

To evaluate in patients with chronic renal failure (CRF) the effectiveness and the costs of sevelamer, a cationic polymer calcium- and aluminum-free, that is a new gastrointestinal phosphate binder. Literature review and critical appraisal of six clinical trials about the effectiveness and two economic studies of sevelamer in CRF patients. Sevelamer is an effective phosphate binder (used in a mean daily dose of 3.5 g three times per day with meals) and with similar effect as that obtained with calcium salts, without the adverse manifestations of the latter (elevation of calcium x phosphorus product, hypercalcemia, vascular and cardiac calcifications, etc.). Moreover, sevelamer reduced serum LDL cholesterol in around 30%. Despite the greater direct costs of sevelamer compared with calcium salts, the total costs may be lower due to the reduction of costs with clinical complications and hospitalizations. Sevelamer has important therapeutic value in CRF patients with hyperphosphatemia. Economic analyses should be performed in our setting to define the cost-effectiveness relationship of sevelamer.

Effect of Phosphate Binders on Supplemental Iron Absorption in Healthy Subjects

A single‐dose, prospective, randomized, four‐treatment, four‐period crossover study was conducted to determine the acute effect of therapeutically equivalent doses of three commonly used phosphate binders on oral iron absorption. Twenty‐three healthy subjects received 65 mg of elemental iron alone and with each phosphate binder (calcium carbonate 3000 mg, calcium acetate 2668 mg, or sevelamer HCl 2821 mg). Area under the change in plasma iron concentration‐time curve over 6 hours postdosing was measured. ANOVA was used to assess the statistical significance of differences in iron absorption among the treatments. The relative bioavailability of iron administered with each phosphate binder compared to iron administered alone was estimated. The relative iron bioavailabilities (95% confidence intervals) for the calcium carbonate, calcium acetate, and sevelamer HCl treatments were 0.81 (0.70, 0.94), 0.73 (0.63, 0.85), and 0.90 (0.78, 1.05), respectively. Thus, single doses of both calcium‐based phosphate binders significantly reduced single‐dose iron absorption, while sevelamer HCl did not.

Therapeutic agents for hyperphosphatemia

Hyperphosphatemia is one of the major causes of secondary hyperparathyroidism (II degrees HPT) in dialysis patients. Aluminum (Al) hydroxide was commonly used as a phosphate binder in Japan until the beginning of the 1990's, when it was replaced by calcium(Ca) compounds to eliminate undesirable side effects. Although Ca compounds are effective phosphate binders, the concomitant use of vitamin D derivatives can often result in hypercalcemia. For the reason, physicians today have been requesting phosphate binders that contain neither Al nor Ca. In this paper, we introduce several such phosphate binders. Sevelamer hydrocholoride (SH) is a new phosphate binder that contains neither Al nor Ca, and is not absorbed from the gastrointestinal tract. Several short-term clinical studies have established that SH is as efficient as calcium carbonate at lowering serum phosphorus (P) levels, with significant improvement in the Ca x P product and lipids metabolism. Furthermore, a long-term (52 weeks) study revealed that SH attenuated the progression of coronary and aortic calcification in hemodialysis (HD) patients. SH is considered a highly effective phosphate binder in protecting against the progression of II degrees HPT and cardiovascular death in HD patients.

Effect of phosphate binders on supplemental iron absorption in healthy subjects: MC Pruchnicki, JD Coyle, WH Bay. The Ohio State University, Columbus, OH, USA

Effect of phosphate binders on supplemental iron absorption in healthy subjects: MC Pruchnicki, JD Coyle, WH Bay. The Ohio State University, Columbus, OH, USA

Sevelamer HCL improves parathyroid hormone (PTH) and bone function in peritoneal dialysis (PD) patients with probable low turnover bone disease

SEVELAMER HCL IMPROVES PARATHYROID HORMONE (PTH) AND BONE FUNCTION 1N PERITONEAL DIALYSIS (PD) PATIENTS WITH PROBABLE LOW TURNOVER BONE DISEASE Sharon Mae*, Jan Paterson, Cindy Murphy, Erika Johnson, Mark Deeg. Indiana Univ and Roudebush VAMC, Indpls, IN Patients on PD are more likely to have adynamic or low-turnover bone disease and hypereholesternlemia than are HD patients. Calcium containing phosphate binders may contribute to the high incidence of adynamic bone disease due to the positive calcium balance they induce. We hypothesized that sevelamer HCL (Renagel®, Geltex/Genzyme, 1⁄2c = SEV) may normalize the excessively low PTH levels observed in PD patients because of the decreased calcium load compared to calcium acetate. To test this, we compared these phosphate binders in PD patients who had a persistent PTH < 200 pg/ml, and BAP < 20 IU, on no Vitamin D in a randomized, cross-over design with 12 wk treatment arms. In each man, PTH, BAP, total calcium corrected for albumin (tCa) and ionized calcium (iCa) were measured after a 2 wk washout (=baseline) and every 4 wks for each 12 wk treatment ann. In addition, the subjects had pre and post lipid studies. Five patients completed the study, with one shortened sevelamer (SEV) arm due to diarrhea. Three other patients dropped out due to transpiantatinn and pancreatitis. The PTH decreased from baseline to 12 weeks by 21 ~16 % in the CaA, vs an increase of 47 :k 12 % in the SEV arm (Mean ± SEM, p = 0.05). This occurred despite equivalent tCa (+0.02 ± 0.11 CaA vs +0.15 ± 0.06 mg/dl in SEV), iCa (-0.31 ± 0.19 CaA vs -0.95 :k 0.17 mg/di in SEV), and phosphorus (-0.31 ± 0.19 CaA vs -0.95 ± 0. I7 rag/all in SEV; all p = NS). The BAP decreased in the CaA arm by 1.52 ± 1.06 IV, compared to an increase of 2.20 ± 0.72 IU in the SEV arm (p < 0.007), supporting improved osteuhlast function. The to~al cholesterol was unchanged in the CaA group (9.5 :~ 13.5%) but decreased by 26.9 ~= 22.9% in the SEV arm, p = 0.08, due primarily to changes in LDL. Dietary recall revealed similar calcium, phosphorus, and cholesterol intake in each arm for each patient. In summary, SEV appears to be a safe and effective phosphate binder in PD patients. The rise in PTH and BAP, and decrease in cholesterol indicates sevelamer may offer a distinct advantage over CaA. Larger, long-term studies are required to confirm these f'mdings. 59

Sevelamer with and without calcium and vitamin D: Observations from a long-term open-label clinical trial

Objective: To determine the effects of sevelamer hydrochloride on serum phosphorus, calcium, calcium x phosphate product, and parathyroid hormone (PTH) in patients treated with and without vitamin D metabolites and calcium supplementation. Design: Long-term, open-label clinical trial. Setting: Hemodialysis units. Patients: One hundred ninety-two adult patients with end-stage renal disease on hemodialysis. Intervention: An extended treatment period of sevelamer hydrochloride, preceded and followed by phosphate binder washout periods. Main outcome measures: Treatment-related changes in serum phosphorus, calcium, calcium x phosphate product, and PTH. Results: Subjects treated with sevelamer alone, sevelamer with vitamin D metabolites (with or without calcium), and sevelamer with calcium without vitamin D experienced significant reductions in mean serum phosphorus (range, −2.1 to −2.9 mg/dL) and the calcium x phosphate product (range, −16.3 to −23.4 mg2/dL2). The mean serum calcium concentration increased in all subgroups except those treated with sevelamer alone (range, +0.3 to +0.5 mg/dL). In contrast, only subjects treated concurrently with vitamin D metabolites experienced a reduction in PTH. Subjects treated with sevelamer alone or sevelamer with calcium without vitamin D experienced an increase in PTH with treatment. Conclusion: Sevelamer hydrochloride is a safe and effective phosphate binder in hemodialysis patients. Sevelamer should be used in combination with vitamin D metabolites to jointly control hyperphosphatemia and hyperparathyroidism. Randomized clinical trials will be required to determine the optimal management strategies for metabolic bone disease in end-stage renal disease, as well as less advanced stages of chronic renal insufficiency.

Osteodystrophy in the millennium

Despite three decades of intensive research on the derangements of calcium phosphate metabolism of renal failure, several unresolved issues are still with us at the turn of the millennium: poor control of hyperphosphatemia, relative inefficacy of active vitamin D to prevent progressive parathyroid hyperplasia, and persistence of bone disease despite lowering of parathyroid hormone (PTH) and administration of active vitamin D. Although predictions are problematic, it is not unreasonable to hope that, barring unforeseen side effects, calcimimetics will prove to be valuable for suppressing or even preventing hyperparathyroidism, thus potentially replacing, at least in part, active vitamin D. There is also reason to hope that more effective phosphate binders with fewer side effects will become available and that controlled studies will provide a rationale for the administration of estrogens to dialyzed women. As regards understanding the pathological mechanisms, one can anticipate that the disturbances leading to autonomous growth of parathyroid cells will be elucidated and the signals involved in osteoclast/osteoblast differentiation pathways and osteoclast/osteoblast coupling will be clarified, with obvious impact on patient management.

Efficacy and tolerance of three different calcium acetate formulations in hemodialysis patients

Background: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic renal failure. However, an important side effect is gastro-intestinal discomfort. Phos-ex® (Cablon, The Netherlands) is the only commercially available non-coated CaAc formulation in our country. We developed two new CaAc formulations: neutral-coated CaAc (NCCaAc) and enteric-coated CaAc (ECCaAc).Methods: In a randomised double-blinded cross-over trial we compared efficacy and tolerance of the three formulations in 19 stable hemodialysis patients, with a mean age of 63 years (range, 36–85), who had been on hemodialysis for 19 months (range, 6–47). Patients were randomised to receive NCCaAc or ECCaAc, with meals, for a period of 10 weeks and after cross-over for another 10 weeks. During a third non-blinded period, patients received Phos-ex® for 10 weeks.Results: Serum phosphate was significantly higher with ECCaAc compared to NCCaAc (1.89±0.07 vs. 1.70±0.08 mmol/l, P<0.05). Serum Ca was significantly lower with ECCaAc compared to NCCaAc or Phos-ex® (2.38±0.04, 2.47±0.04 and 2.48±0.04 mmol/l, P<0.05). There were less hypercalcemic and more hyperphosphatemic events in the ECCaAc period, compared to the other periods. The daily CaAc dose and dietary intake of calcium, phosphate, protein and calories were comparable in all three periods. With Phos-ex®, patients noticed more gastro-intestinal complaints than with to NCCaAc and ECCaAc. Two patients stopped taking Phos-ex® because of side effects.Conclusions: In hemodialysis patients, phosphate control and tolerance were both influenced by the formulation of CaAc. Although phosphate control was adequate with all three formulations of CaAc, ECCaAc was less effective compared to NCCaAc or Phos-ex®. NCCaAc and ECCaAc were better tolerated than Phos-ex®. Regarding efficacy and tolerance, NCCaAc was the best calcium acetate formulation.

RenaGel®, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone

This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids. Phosphate binders were discontinued during a two-week washout period. Patients whose serum phosphorus was more than 6.0 mg/dl during washout were eligible for treatment. RenaGel(R), at starting doses of two, three, or four 440 mg capsules three times per day with meals, was administered to 172 hemodialysis patients for eight weeks. RenaGel(R) could be increased by one capsule per meal every two weeks as necessary to achieve serum phosphorus control. A second two-week washout period followed. Mean serum phosphorus rose from 6.8 +/- 2.0 mg/dl at prewashout to 9.1 +/- 2.4 mg/dl at the end of the washout period. It then declined to 6.6 +/- 1.9 mg/dl by the end of the eight-week RenaGel(R) treatment period (P < 0. 0001). Serum phosphorus increased to 8.0 +/- 2.2 mg/dl at the end of the second washout period. The mean dose at the end of RenaGel(R) treatment was 5.4 g per day. Eighty-four percent of the patients previously used calcium-based phosphate binders. As expected, calcium declined during the initial washout period when calcium-based phosphate binders were discontinued. Mean serum calcium declined from 9.6 +/- 1.0 mg/dl at prewashout to 9.1 +/- 0.8 mg/dl after washout. It then increased to 9.4 +/- 0.9 mg/dl by the end of RenaGel(R) treatment. Median serum iPTH increased during the two-week washout from 208 pg/ml to 316 pg/ml and then declined to 224 pg/ml at the end of the eight-week treatment period (P < 0.0001 vs. end of initial washout). After eight weeks of treatment, RenaGel(R) reduced mean serum total cholesterol from 171.0 +/- 43.1 mg/dl to 145.0 +/- 38.7 mg/dl (P < 0.0001) and mean serum low-density lipoprotein cholesterol from 102.0 +/- 34.9 mg/dl to 75. 6 +/- 29.4 mg/dl (P < 0.0001). High-density lipoprotein cholesterol, triglycerides, and serum albumin did not change. RenaGel(R), a novel and calcium- plus aluminum-free effective phosphate binder, can control serum phosphorus and reduce the levels of PTH and cholesterol without inducing hypercalcemia or other side effects. Thus, this new phosphate binder may be effective in the treatment of renal osteodystrophy in uremic patients.

Intradialytic Calcium Balances with Different Calcium Dialysate Levels

It has been shown that calcium carbonate (CaCO3) is an effective phosphate binder which is less toxic than Al(OH)3. However, given that its use with standard calcium dialysate (CaD) levels may lead to hypercalcemia, a decrease in CaD levels has been proposed. The aim of the present study was to elevate the acute clinical and biochemical consequences of a lowering of CaD in HD patients. Dialysate composition was otherwise the same. (1) Blood pressure levels (BP) during short hemodialysis were measured in a group of 12 patients who underwent alternate hemodialyses with dialysate calcium of 1.75 and 1.25 mmol/l. (2) Ca2+ and PTH kinetics during short hemodialysis were studied in a group of 6 patients who were sequentially treated with 1.75 and 1.25 mmol/l CaD. The results show: (1) that cardiovascular stability in chronic HD patients during short HD sessions with low CaD (LCaD) may be good; (2) that a single treatment with standard CaD (SCaD) produces positive calcium balances (JCa2+) with Ca2+ plasma increase and PTHi inhibition at the end of HD sessions; during HD with LCaD there were neutral mean JCa2+ and no changes in post-dialysis mean Ca2+ and PTHi plasma levels; furthermore 2 patients showed a small PTHi increase during HD with LCaD and neutral JCa2+ because of a high positive bicarbonate balance during HD. In conclusion, as with several aspects of dialysis treatment, dialysate calcium levels should also be individualized to avoid hypercalcemic crises or PTHi stimulation.

Low and High Turnover Bone Disease in Continuous Ambulatory Peritoneal Dialysis: Effects of Low-Ca + Peritoneal Dialysis Solution

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.

Low Calcium Peritoneal Dialysis Solution

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (AI) intake. By maintaining high serum Ca2+ levels, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. To evaluate the effects of a low Ca2+ peritoneal dialysis solution (PDS; 1.25 mmol/L) on calcium metabolism, the following were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (six with high PTH levels, and high turnover bone disease [Group 1], and six with low PTH levels, and low turnover bone disease [Group 2] documented by bone biopsies): 1) serum Ca2+ and PO4 levels; 2) serum PTH levels; 3) serum AI levels; and 4) bone morphology. The follow-up was 12 months. In both groups, within the third month, there was a decrease in serum Ca2+. In Group 2, serum PTH increased, reaching the norm, and in Group 1 it further increased, exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to give oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels while stopping AI gels. This did not induce any increase in serum Ca2+, whereas serum AI fell significantly. In Group 1, to avoid a further rise of serum PTH, the low Ca2+ PDS was supplemented with calcitriol (mean 3.5 +/- 0.5 microgram/day); this was followed by a reduction in serum PTH with no increase in serum Ca2+ or PO4.(ABSTRACT TRUNCATED AT 250 WORDS)

Audit of the use of calcium carbonate as a phosphate binder in 100 patients treated with continuous ambulatory peritoneal dialysis.

We studied the effect of converting 100 established CAPD patients from aluminium- to calcium-based phosphate binders. After a follow-up of 1 year only 60% of patients remained on calcium carbonate. Hypercalcaemia was the major problem, with more than 40% of patients having a serum calcium in excess of 3.0 mmol/l. Several patients required hospitalization for symptomatic hypercalcaemia. Hypercalcaemia was more common in patients with normal serum parathyroid hormone concentrations (65 versus 25%, P less than 0.01). Serum phosphate control was better prior to commencing calcium carbonate when patients were treated with aluminium phosphate binders mean 1.71 +/- 0.15 mmol/l (SEM) than at the time of maximum serum calcium concentration, 1.81 +/- 0.25, P less than 0.05. This study does not confirm the findings of others, which have suggested that calcium carbonate is a safe and effective phosphate binder for patients with end-stage renal failure.

Calcium Carbonate 1250mg/1260mg: An Effective Phosphate Binder

Calcium carbonate is currently the first choice phosphate binder in renal failure. In the UK its most widely prescribed formulation is a combination of calcium carbonate 420 mg and glycine 180 mg (Titralac 3M Riker). In order to achieve adequate reduction in the serum phosphate level, up to 12 of these tablets may be required daily. In a group of seven patients, we have compared Titralac with two alternative preparations containing calcium carbonate 1250 mg (Calcium-500 Macarthy's Medical Ltd) and calcium carbonate 1260 mg (Calcichew Shire Pharmaceuticals Ltd). Given at a third of the daily number of Titralac tablets, both these newer preparations were effective phosphate binders and produced no statistically significant change in serum calcium and phosphate. The important advantage of such a reduced tablet load is improved patient compliance with phosphate binder therapy. Calcium-500 is also a cost-effective treatment slightly reducing the cost when compared with combined calcium carbonate 420 mg and glycine 180 mg.

Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism

Many investigators have shown that calcium carbonate (CaCO3) is an effective phosphate binder which also prevents the potential disabling effects of aluminum (Al) accumulation. However, hypercalcemia may develop in a substantial numbers of patients. Thus, to control serum phosphate (PO4) and prevent hypercalcemia, we performed studies in 21 patients on maintenance hemodialysis in which, in addition to the oral administration of CaCO3, the concentration of calcium (Ca) in the dialysate was reduced from 3.25 to 2.5 mEq/liter. The studies were divided in three periods: I. control, on Al-binders (one month); II. no Al-binders (one month); III. CaCO3 (seven months). Blood was obtained three times/week before dialysis for the first five months of the study and once a week for the remaining four months. During the control period, the mean serum calcium was 8.86 +/- 0.08 mg/dl. The value decreased to 8.65 +/- 0.07 mg/dl when phosphate binders containing aluminum were discontinued, and increased to 9.19 +/- 0.07 mg/dl (P less than 0.001 compared to period II) during oral supplementation with calcium carbonate. The mean serum phosphorus was 5.03 +/- 0.07 mg/dl during the control period, and increased to 7.29 +/- 0.91 mg/dl (P less than 0.001) after phosphate binders were discontinued. It decreased to 4.95 +/- 0.06 mg/dl (P less than 0.001) with the administration of calcium carbonate. During CaCO3 administration, serum Al decreased from 64.2 +/- 8.5 to 37.1 +/- 3.6 and 25.1 +/- 3.0 micrograms/liter (P less than 0.001) at three and seven months, respectively. Serum parathyroid hormone (PTH) decreased by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Carbonate Powder as a Phosphate Binder

With increasing recognition of problems regarding the use of aluminum hydroxide as a phosphate binder, calcium carbonate has become the medication of choice. Use of calcium has, however, frequently been associated with development of hypercalcemia. At this institution, calcium carbonate powder as a phosphate binder, examination of its efficacy, and the frequency of hypercalcemia with its use were of great interest. Calcium carbonate powder (CalCarb-HD, 2.4 gms elemental calcium/packet) (CalCarb-HD, Lafayette Pharmacal Inc., Fort Worth, TX) was used in the study. Twenty-one end-stage renal disease (ESRD) patients (17 hemodialysisand 4 chronic ambulatory peritoneal dialysis) were chosen and converted from their previous binder (primarily, calcium carbonate tablets) to calcium powder. The dosage was adjusted to keep phosphorus levels at 3.5 to 5.5 mg/dl and calcium < 11.5 mg/dl. At 2 months, the average calcium level in the 16 patients remaining in the study was 9.2 mg/dl, and the average phosphorus level was 5.2 mg/dl with an average calcium dose of 1.4 packets/day. By 7 months, the 8 patients remaining in the study had an average calcium level of 9.9 mg/dl with an average phosphorus level of 5.5 mg/dl; average calcium dose was 1.8 packets/day. Total episodes of hypercalcemia (calcium greater than 11.5 mg/dl) were two. Calcium carbonate powder appears to be an effective phosphate binder in the ESRD population. The relatively few episodes of hypercalcemia may be related to possible enhanced bioavailability of the compound secondary to its powdered form.

Calcium carbonate powder as a phosphate binder.

With increasing recognition of problems regarding the use of aluminum hydroxide as a phosphate binder, calcium carbonate has become the medication of choice. Use of calcium has, however, frequently been associated with development of hypercalcemia. At this institution, calcium carbonate powder as a phosphate binder, examination of its efficacy, and the frequency of hypercalcemia with its use were of great interest. Calcium carbonate powder (CalCarb-HD, 2.4 gms elemental calcium/packet) (CalCarb-HD, Lafayette Pharmacal Inc., Fort Worth, TX) was used in the study. Twenty-one end-stage renal disease (ESRD) patients (17 hemodialysis and 4 chronic ambulatory peritoneal dialysis) were chosen and converted from their previous binder (primarily, calcium carbonate tablets) to calcium powder. The dosage was adjusted to keep phosphorus levels at 3.5 to 5.5 mg/dl and calcium less than 11.5 mg/dl. At 2 months, the average calcium level in the 16 patients remaining in the study was 9.2 mg/dl, and the average phosphorus level was 5.2 mg/dl with an average calcium dose of 1.4 packets/day. By 7 months, the 8 patients remaining in the study had an average calcium level of 9.9 mg/dl with an average phosphorus level of 5.5 mg/dl; average calcium dose was 1.8 packets/day. Total episodes of hypercalcemia (calcium greater than 11.5 mg/dl) were two. Calcium carbonate powder appears to be an effective phosphate binder in the ESRD population. The relatively few episodes of hypercalcemia may be related to possible enhanced bioavailability of the compound secondary to its powdered form.

Recent developments in aluminum toxicology.

Aluminum is now recognised as an important toxin causing considerable morbidity and mortality, particularly in patients with chronic renal failure. Diseases that have been associated with aluminium include dialysis dementia, renal osteodystrophy and Alzheimer's disease. Aluminum also has an effect on red blood cells, parathyroid glands and chromosomes. Accumulation of aluminium in the body tends to occur when the gastrointestinal barrier is circumvented. This has been identified as a problem during dialysis or intravenous fluid administration. Renal functional impairment results in decreased aluminum excretion and promotes accumulation of the element in the body. Many sources have been shown to be contaminated with aluminium. These include the water used for dialysis; medicines containing aluminium, such as aluminium-containing phosphate binding gels; total parenteral nutrition solutions; processed human serum albumin; intravenous fluids in infants; and other environmental and industrial sources. The management of aluminium toxicity involves the identification of these contaminated sources and subsequent removal of the element. This includes regular monitoring of water used in dialysis. The use of aluminium-containing phosphate binding gels in patients with compromised renal function should be reviewed and alternatives sought. The development of effective aluminium-free phosphate binders is desirable. Once a patient has aluminium toxicity, desferrioxamine (deferoxamine) has been shown to be an effective agent in its chelation and removal.

Effect of phosphate binders on the course of chronic renal failure in rats with focal glomerular sclerosis.

To investigate the effect of phosphate binders on the progress of renal functional deterioration, aluminium hydroxide (AL) or calcium carbonate (CA) was administered to adriamycin (ADR)-induced progressive renal failure model rats. Urinary protein excretion was reduced in ADR rats treated with AL (ADR-AL group) or CA (ADR-CA group), compared to those without the treatment (ADR group). Urinary phosphate excretion, serum phosphate concentration, and calcium-phosphate product were significantly lower in the ADR-AL and ADR-CA groups than in the ADR group. At week 34, increased serum creatinine, glomerular sclerosis and tubulointerstitial alterations, being marked in the ADR group, were ameliorated in the ADR-AL and ADR-CA groups. However, there was no significant difference in body weight and serum total protein among the three groups. We conclude that AL and CA could both prevent chronic progressive renal deterioration in focal glomerular sclerosis induced by ADR, and preserve the nutritional condition.