Control Of Serum Phosphate Levels Research Articles

Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial

BackgroundMagnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO3) as a phosphate-binder in hemodialysis patients.MethodsForty-six stable hemodialysis patients were randomly allocated to receive either MgCO3 (n = 25) or calcium carbonate (CaCO3), (n = 21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO3 group and 0.48 mmol/l in the CaCO3 group.ResultsOnly two of 25 patients (8%) discontinued ingestion of MgCO3 due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO3 and CaCO3 groups, respectively, time-averaged (months 1–6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P = ns; Ca, 9.13 vs. 9.60 mg/dl, P < 0.001; Ca × P product, 50.35 vs. 50.70 (mg/dl)2, P = ns; Mg, 2.57 vs. 2.41 mg/dl, P = ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P < 0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P = ns. At month 6 the percentages of patients with serum levels of phosphate, Ca × P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO3 group (17/23; 73.91%) than in the CaCO3 group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P < 0.01.ConclusionOur study shows that MgCO3 administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO3 in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia.

Pathogenesis of vascular calcification in chronic kidney disease

Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the progression of secondary hyperparathyroidism with the concomitant bone loss, possibly linked to vascular calcium-phosphate precipitation. Results. The control of serum phosphate levels reduces vascular calcification not only by decreasing the degree of secondary hyperparathyroidism and calcium-phosphate product, but also by reducing the expression of proteins responsible for active bone mineral deposition in cells of the vasculature. The calcium and aluminum-free phosphate-binders provide a new and effective therapeutic tool in preventing vascular calcifications in chronic kidney disease in animal models and in hemodialysis patients. Conclusion. Additional investigations are necessary to examine the benefits of different phosphate-binders in reducing mortality from cardiovascular disease.

Control of serum phosphate by oral lanthanum carbonate in patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis in a short-term, placebo-controlled study

Hyperphosphataemia in dialysis patients is associated with significant morbidity. We assessed the ability of lanthanum carbonate to control phosphate levels in patients undergoing haemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in a short-term, placebo-controlled study. This was a double-blind, placebo-controlled, parallel-group study consisting of three phases: a 2 week washout period; a 4 week, open-label, dose-titration phase; and a 4 week, double-blind, placebo-controlled phase. After washout, patients (n = 59) received lanthanum (375 mg/day), titrated up to a maintenance dose (maximum: 2250 mg) that achieved control of serum phosphate levels between 1.3 and 1.8 mmol/l (4.03-5.58 mg/dl). After titration, patients were randomized to receive their maintenance dose of lanthanum (n = 17) or placebo (n = 19) for 4 weeks. Control of serum phosphate was the primary efficacy assessment. Levels of calcium, parathyroid hormone, calcium x phosphate product and lanthanum as well as adverse events were evaluated. By the end of titration, 70% of patients had serum phosphate levels < or =1.8 mmol/l. Lanthanum carbonate continued to control serum phosphate levels in the double-blind phase. At the end of the study, 64.7% of lanthanum carbonate-treated patients were controlled compared with 21.4% in the placebo group. Results in patients receiving CAPD were similar to those seen in the group as a whole. Mean parathyroid hormone levels (P = 0.41) and calcium x phosphate product (P<0.001) were both higher in the placebo than the lanthanum carbonate group. Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and calcium x phosphate product.

Calcium and phosphate balance with quotidian hemodialysis

Background: Conventional hemodialysis (HD) is associated with profound disturbances in calcium and phosphate metabolism and abnormal parathyroid hormone (PTH) levels. Effects of more frequent HD on calcium and phosphate balance have not been fully elucidated. Methods: The London Daily/Nocturnal Hemodialysis Study examined effects of quotidian HD, either daily HD (n = 11) or nocturnal HD (n = 12), on calcium and phosphate metabolism, bone alkaline phosphatase levels, and intact PTH (iPTH) levels. Results: Daily HD patients showed a slight decrease in predialysis serum phosphate levels, no changes in phosphate-binder requirements or serum calcium levels, and slight increases in serum bone alkaline phosphatase and iPTH levels. Nocturnal HD patients showed a trend for decreased predialysis phosphate levels, with significantly lower values than daily HD and matched control patients on conventional HD therapy at several times. Phosphate-binder use by nocturnal HD patients was significantly reduced. Both quotidian HD groups showed decreases in calcium × phosphate product, with significantly lower values for nocturnal HD patients (38.11 mg 2/dL 2) compared with daily HD and control patients (53.99 and 52.51 mg 2/dL 2, respectively) at 18 months. Bone alkaline phosphatase levels increased slightly and attained statistical significance compared with baseline values for both quotidian HD groups. A trend for increases in serum iPTH levels, coupled with increasing levels of bone alkaline phosphatase in nocturnal HD patients, led to the decision to increase the dialysate calcium concentration from 5.0 to 7.0 mg/dL. This 1-time adjustment resulted in a reversal of the trend and a return to baseline values. Conclusion: This study shows the superior control of serum phosphate levels in nocturnal HD patients compared with daily HD or conventional HD patients and the benefits of dialysate with a greater calcium concentration in slow nocturnal HD.

Hyperphosphatemia and diet therapy

Hyperphosphatemia cause not only renal bone disease but also poor prognosis in hemodialysis patients. We should control serum phosphate levels within near normal range. Although many patients are prescribed phosphate binder, they should restrict oral phosphate intake. There are poor prognosis in malnutrition patients, they should take sufficient protein. Contents of phosphate in foods increase proportionaly with protein contents. It is important that they should take foods with low phosphate contents and low phosphate/protein ratio. They should restrict preserved food, confectionary, seasoning which contain phosphate compounds as food additive. It is useful to take special low phosphate food.

Hyperphosphatemia in end-stage renal disease.

Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD.

Secondary Causes of Osteoporosis

Secondary Causes of Osteoporosis

Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis

We compared the efficacy and the long-term effects of nocturnal hemodialysis (NHD) versus conventional hemodialysis (CHD) in controlling serum phosphate levels in patients with end-stage renal disease (ESRD). Patients underwent thrice weekly CHD and were subsequently switched to NHD six nights weekly. In the "acute" study serum and dialysate phosphate were measured during and after dialysis, and the total dialysate was collected to calculate mass solute removal. Although pre-dialysis (1.7 +/- 0.6 vs. 1.5 +/- 0.8 mM) serum phosphate levels were similar in CHD and NHD, respectively, post-dialysis levels were slightly lower with CHD (0.7 +/- 0.2 vs. 0.8 +/- 0.2 mM, P < 0.05). The measured phosphate removed per session of CHD or NHD was comparable, 25.3 +/- 7.5 versus 26.9 +/- 9.8 mumol/session, respectively. On the other hand, the cumulative weekly phosphate removal was significantly higher with NHD as compared to CHD, 75.8 +/- 22.5 versus 161.6 +/- 59.0 mumol/week (P < 0.01). In the "chronic" study serum phosphate levels were measured monthly for five months on CHD and for five months after the patients were switched to NHD. Dietary phosphate intake and the dosage of phosphate binders were tabulated. Serum phosphate levels fell during NHD: 2.1 +/- 0.5 mM at the beginning of the study and 1.3 +/- 0.2 mM five months after being switched to NHD (P < 0.001). At the same time dietary phosphate intake increased by 50%. By the fourth month of NHD therapy none of the patients was taking any phosphate binders. In conclusion, NHD is more effective in controlling serum phosphate levels than CHD, allowing patients to discontinue their phosphate binders completely and to ingest a more liberal diet.

Niceritrol decreases serum phosphate levels in chronic hemodialysis patients

Since phosphorus retention in hemodialysis (HD) patients is known to be an important factor in the development of secondary hyperparathyroidism and renal osteodystrophy, phosphate binders have been needed for the control of serum phosphate levels (P). However, the calcium-containing phosphate binders that have been used widely can cause a rise in serum calcium levels and cause secondary hypoparathyroidism. We have recently experienced decreases in P after the administration of niceritrol (NT), a prodrug of nicotinic acid, for the treatment of low HDL-cholesteremia (HDL-C) in HD patients. The aim of the present study was to assess the mechanism of the P-lowering effect of NT in comparison with nicomol (NC), another prodrug of nicotinic acid. NT (750 mg/day) or NC (600 mg/day) was given orally to 10 or 14HD patients respectively. Blood samples were collected before the first dialysis of each week for the determination of serum urea nitrogen (UN), Cr, Ca, P, total cholesterol (TC), triglyceride (TG) and HDL-C. Serum nicotinic acid concentration (NAC) by gas chromatograph mass-spectrometry method was determined before, 4 weeks and 8 weeks after the administration of these drugs. After NT administration, P was decreased from 6.2 +/- 0.4 mg/dl to 5.1 +/- 0.4 mg/dl (1st week, p < 0.001, Mean +/- SE) and 4.5 +/- 0.3 mg/dl (2nd weeks, p < 0.001) with no change in UN, Cr or Ca levels; these significant decreases in P lasted for 8 weeks. NAC increased significantly after NT administration from 25.5 +/- 1.3 ng/ml to 549.8 +/- 102.2 ng/ml (4 weeks, p < 0.01) and 431.7 +/- 51.4 ng/ml (8 weeks, p < 0.01). HDL-C also increased (33.6 +/- 4.0 mg/dl vs 42.7 +/- 4.6 mg/dl, p < 0.05), but TC and TG did not change. In contrast, no significant changes were observed in P, NAC and HDL-C after NC administration. These discrepancies could be ascribed to the differences in serum NAC levels. These data suggest that NT could be useful for the control of P in HD patients. However further studies are needed to confirm the mechanism of the P-lowering effect of NT.

Phosphate removal in haemodialysis: Effect of two different dialysis membranes

Summary: Phosphate removal with two different dialysis membranes (a standard cellulose acetate membrane and a high performance cellulose diacetate membrane) were studied in ten haemodialysis patients. All patients were dialysed sequentially with two membranes (surface area was 1.5 m2) against bicarbonate buffered dialysis for 4 hours three times a week. With the diacetate membrane, the instantaneous clearances of urea and phosphate after 1 hour of haemodialysis were significantly higher than with the cellulose membrane. Also, the weekly total amount of urea and phosphate removal were significantly increased with the diacetate membrane (a 15% increase in urea and a 16% increase of phosphate). Although there was a significant increase in urea reduction ratio and significantly lower post dialytic plasma urea concentration with the diacetate membrane, these for phosphate did not reach statistical significance. These data suggest that the use of the diacetate membrane potentially offer clinical benefit. However, whether 16% of phosphate removal could improve clinical control of serum phosphate levels will need further investigation.

Crystal-induced arthritis: An overview

The most common crystal-related arthropathies-gout, calcium pyrophosphate dihydrate disease or "pseudogout," and calcific periarthritis/tendinitis-may be appropriately diagnosed and managed by the primary care physician. Definitive diagnosis via synovial tap is recommended, as the clinical picture may not identify some cases. The acute pain and swelling of attacks, regardless of etiology, generally respond to treatment with nonsteroidal anti-inflammatory drugs and local or occasionally systemic corticosteroids. Once a causative crystal has been identified and a diagnosis established, a plan for long-term management and prevention of recurrences may be devised. Thus, uric-acid-lowering therapy may be indicated in a patient who has experienced recurrent attacks of gout, whereas control of serum phosphate levels might be effective in some individuals with hyperphosphatemia and hydroxyapatite-associated periarthritis or arthritis. Crystal deposits in joints can be destructive as well as painful. Treatment, therefore, has two objectives: To relieve the pain of the acute attack, thus restoring normal function, and to prevent the accumulation of crystals that can lead to degenerative disease. Identification and subsequent treatment of preventable or correctable underlying disorders may be one of the most gratifying aspects of managing crystal-induced arthropathies.

Serum concentrations of calcitriol and PTH in hemo-dialysis patients on treatment with calcium carbonate.

The effects of calcium carbonate and aluminium hydroxide as phosphate binders were investigated in nine patients on chronic hemodialysis. Aluminium hydroxide, 1 g X 3, was given during four weeks followed by a period of four weeks without any phosphate binders and after this calcium carbonate, 2.5 g X 3, was introduced for four weeks. Calcium carbonate resulted in lowering of bioactive PTH in serum from 22.4 to 16.4 pM and a rise of serum calcitriol from 8.0 to 11.5 pg/ml with maintained control of phosphate and without significant difference in the calcium-phosphate product. Calcium in serum rose from 2.27 to 2.57 mM and mild hypercalcemia (less than 3.0 mM) in five of the patients could be controlled by dose reduction of calcium carbonate without losing control of serum phosphate levels. We conclude that calcium carbonate offers advantages as a phosphate binder compared to aluminium hydroxide in that it offers equal control of serum phosphate and elevates serum calcium which helps to control the hyperparathyroidism secondary to uremia.

Comparison of Control of Serum Phosphate Levels during Continuous Ambulatory Peritoneal Dialysis and during Hemodialysis

Recent reports have suggested that oral aluminium hydroxide carries the risk of aluminium toxicity. We have compared the aluminium hydroxide dose and serum levels of phosphate and aluminium in 27 CAPD and 26 hemodialysis patients. Despite a more liberal protein intake and lower aluminium hydroxide dose, the CAPD patients achieved the same serum phosphate level as those on hemodialysis. While the reason for more efficient serum phosphate control with CAPD is uncertain, the better control gives CAPD an advantage in patients in whom it is particularly important to minimise exposure to aluminium.

Calcium metabolism in renal failure

Osteodystrophy is almost universally present in chronic renal failure. Mild, but detectable, abnormalities—especially in parathyroid hormone (PTH) secretion—occur even when the glomerular filtration rate is greater than 30 cc/min. Osteomalacia is common in areas in which vitamin D intake and exposure to sunlight are minimal; when these factors are plentiful, osteitis fibrosa predominates. Osteoporosis is seen with increasing frequency in hemodialyzed patients. Nonosseous complications of secondary hyperparathyroidism include hypercalcemia, metastatic calcification and pruritus. The most important factor in the medical therapy of Osteodystrophy is control of serum phosphate levels. Next, a positive calcium balance must be provided either by giving vitamin D as dihydrotachysterol, raising dialysate calcium or administering calcium orally. Parathyroidectomy is sometimes indicated, especially when the patients are transplant candidates and manifest hypercalcemia. Whether or not transplant is contemplated, patients with persistently high calcium-phosphate products, severe metastatic calcification or rapidly progressive Osteodystrophy should be considered for parathyroidectomy. Newer, experimental vitamin D preparations, such as 1,25-dihydroxycholecalciferol or 1-alpha-hydroxycholecalciferol, should improve the management of patients with renal Osteodystrophy and decrease the need for parathyroidectomies.