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Vascular calcification is the abnormality in chronic kidney disease-mineral bone disorder (CKD-MBD) that directly affects the prognosis in relation with cardiovascular diseases. Phosphate binders (PB) are widely used to prevent hyperphosphatemia that can lead to vascular calcification. Two types of PB are available ; calcium (Ca) -based PB and non-Ca-based PB. Non-Ca-based PB has been shown to retard the progression of vascular calcification, while there is a great concern that Ca overload can promote calcification. Moreover, the newer non-Ca-based PBs have been developed including iron and magnesium. We must pay attention to select proper types of PB with costs, pill burdens and specific circumstances observed in Japan.

Pharmacoeconomics (PE) , which contributes to the decisions on the population rather than the patient level such as policy making, provides us with the cost and value of a given drug. Recent Japanese PE studies in the field of CKD-MBD are reviewed in this manuscript. Lanthnum carbonate is not cost effective as a first-line phosphate binder, while cost effective as a second-line drug added on conventional treatments for those with serum phosphate >6.0 mg/dL, as shown in incremental cost-effectiveness ratio (ICER) of $34,896. Cinacalcet hydrochloride was found to be cost effective only for those who cannot undergo parathyroidectomy. Taking these findings into account, when cinacalcet have to be used, we should give priority to calcium containing phosphate binders rather than expensive sevelamer or lanthanum from the viewpoint of the medical cost. Moreover, the doses of cinacalcet should be minimized by administering inexpensive vitamin D concomitantly.

Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Especially in end stage renal disease (ESRD) patients, the nutritional disturbance due to strict phosphate restriction with protein restriction is certainly associated with patients' survival. Firstly, the aggressive phosphorus removal by blood purification modality is also important for the good control in serum phosphate level. Secondary, the active phosphate binder therapy is actual effective treatment for ESRD patients with hyperphosphatemia. Until recently, none of the available agents fulfilled the criteria of an ideal phosphate binders. However, several phosphate binder such as calcium carbonate, sevelamer hydrochloride, lanthanum carbonate and so on, are available in Japan. This review work is describing about the history and clinical manifestation of these phosphate binders.

The one of the main concept of CKD-MBD theory is to prevent and to retard progression of vascular calcification. Recently many basic researches have approached to clear the mechanism of uremic specific vascular calcification. However it remains unclear in clinical setting what examination is best for evaluating vascular calcification. Moreover it is still not sure whether the management based on guidelines can prevent progression of vascular calcification or not in CKD patients. We review about the most accessible clinical factors for vascular calcification.

Hyperphosphatemia with decline of kidney function has been associated with increased mortality and the development of cardiovascular calcification. Sevelamer hydrochloride was the first synthetic non-aluminum and calcium-free phosphate binder commercially available. Sevelamer is as effective as calcium-based binders in lowering phosphate, but without the tendency to promote hypercalcemia. There is some evidence that sevelamer hydrochloride can attenuate cardiovascular calcification compared with calcium-based phosphate binders. Furthermore, sevelamer has several additional pleiotropic effects that may extend its basic indication, some of which may help attenuate vascular calcification. These includes effects on lipid metabolism, and systemic inflammatory response.

The final goal of CKD-MBD (chronic kidney disease, mineral and bone disorder) is to reduce the risk of death in uremic patients. To achieve this objective, it is of importance to manage laboratory abnormalities, bone abnormalities, and vascular calcification appropriately. Many observation studies suggested that the good control of serum phosphate, calcium, and PTH concentration would lead to the lower risk of death. Fracture and vascular calcification would increase the risk for mortality. In addition, some randomized clinical trials have shown that the use of CKD-MBD related drugs, e.g. vitamin D, phosphate binder, might lead to reductions in the risk of death.

The term "renal osteodystrophy" has recently been replaced with "CKD-mineral and bone disorder (CKD-MBD)", which includes vascular calcification as well as bone abnormalities. Following this paradigm shift, the Japanese Society for Dialysis Therapy released guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients, which prioritized improvement in survival, but not in bone abnormalities. According to these guidelines, parathyroid intervention, such as parathyroidectomy and percutaneous ethanol injection therapy, should be indicated if mineral disorders cannot be managed by pharmacological means. Recently, several novel therapeutic tools, including sevelamer hydrochloride, calcitriol analogs, and cinacalcet hydrochloride have been introduced in the clinical setting in Japan. The other side 2009 KDIGO guideline suggest that, if the intact PTH levels fall below two times the upper limit of normal for the assay, calcitriol, vitamin D analogs, and/or calcimimetics be reduced or stopped. And in patients with CKD stages 3-5D with severe hyperparathyroidism (HPT) who fail to respond to medical/pharmacological therapy, this guideline suggest parathyroidectomy. Harmonizing these therapeutic modalities and parathyroid interventions, we should expect more effective management of CKD-MBD, leading to the improvement of morbidity and mortality in this patient population. In this part, we consider indication of parathyroid interventions surround the present condition.

Recently, much of the attention given to bone-mineral disorder as the prognostic factor for mortality has focused on their links to chronic kidney disease (CKD-MBD; chronic kidney disease-mineral bone disease), especially in dialysis patients. Bone disease in dialysis patients showed heterogeneity caused by multiple factors other than postmenopausal osteoporosis. Evaluation of the bone mineral density with DEXA and the bone metabolic markers becomes useless for the assessment of bone fragility in dialysis patients. Prevalence of bone fracture in end-stage renal disease patients is 3-4 times higher than that in general population. The skeletal fracture in ESRD patients is suggested to be related with malnutrition. Guidelines of the therapy for bone-mineral disorder in dialysis patients is centered on the prevention of cardio-vascular disease and the mortality. Physicians should carefully understand these effects in the daily clinical practices.

Higher levels of serum phosphate are associated not only with progression of secondary hyperparathyroidism but also adverse cardiovascular outcomes, such as ectopic calcifications, cardiovascular events its death. The treatments of hyperphosphatemia with phosphate binders were shown to be effective on a risk factor for cardiovascular disease and mortality on hemodialysis patients.

In spite of various cause of hyperphosphatemia, there is a limited number of modality which include restriction of phosphate intake, phosphate binder, extra cellular fluid expansion and blood purification. Each therapy has certain deficit but combination of those may get preferable consequence. Now various new phosphate binders and the inhibitors of sodium-dependent phosphate transporters are being developed. Those agents might promise a better outcome of the treatment of hyperphosphatemia.

Pharmacoeconomics (PE) , which contribute to the decisions on the population rather than the patient level such as policy making, provides us with the cost and value of a given drug. In the midst of terrible economic climate, medications for CKD-MBD are reviewed from the viewpoint of PE in this manuscript. DCOR trial is the only study in maintenance hemodialysis patients with mortality as a primary endpoint, which compared expensive sevelamer hydrochloride and economical calcium containing phosphate binders, showing no difference in mortality between these drugs. This means that calcium containing phosphate binders are more cost-effective. Cost utility analysis from the United States revealed that parathyroidectomy became more cost-effective at 16 months than cinacalcet hydrochloride, which theoretically have to be continued throughout life. The effect of active vitamin D on mortality is controversial, since there has not been any prospective randomized controlled trial. Taking these findings into account, cinacalcet should be indicated only in those patients who have secondary hyperparathyroidism refractory to conventional therapy and for whom parathyroidectomy is not a good indication. Furthermore, when cinacalcet have to be used, we should give priority to calcium containing phosphate binders rather than expensive sevelamer from the viewpoint of the medical cost. Moreover, the doses of cinacalcet should be minimized by administering inexpensive vitamin D concomitantly.

Vascular calcification is associated with the mortality of patients with chronic kidney disease (CKD) . Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascular calcification and is a nontraditional risk factor for CVD mortality in CKD patients. Hyperphosphatemia promotes vascular calcification in part by promoting VSMCs to undergo an osteochondrogenic phenotype change through a mechanism requiring sodium-dependent phosphate cotransporters. Recent randomized clinical trials showed that lowering serum phosphate levels with a non-calcium containing phosphate binder slows progression of vascular calcification in ESRD patients. Moreover, calcimimetics reduce arterial remodeling and calcification in rats with subtotal nephrectomy. Whether this difference will also be found in humans and will ultimately translate into less CV events in calcimimetics treated uremic patients is for a matter for speculation. Calcium and phosphate load are an important driver of vascular calcification.

Introduction of CKD-MBD changed clinical attitudes for the therapy of metabolic bone disease in maintenance dialysis therapy as the systemic diseases of calcium phosphate metabolism. We present the variation of target serum calcium, phosphate and parathyroid hormone levels in the guidelines of US and European countries. We also review the management of drug use especially concomitant active vitamin D metabolites and calcium carbonate to cinacalcet prescription.

Despite phosphate binders are necessary for the control of hyperphosphatemia in chronic kidney disease, adherence to medication tends to be low due to the lack of subjective symptoms of patients. Such non- adherence often causes compromised health outcomes. Key factors affecting adherence of phosphate binders are being the occurrence of side effects such as constipation, taking a lot of tablets, being lack of motive for medication. Thus, to facilitate the adherence of phosphate binders, it is recommended to select medication properly according to the situation of individual patients, to consider the side effect reduction and to raise motive of adherence by educational interventions and drug counseling.

Numerous experimental and clinical studies have recently addressed the underlying mechanisms in particular the marked increase in cardiovascular mortality in patients with CKD. Hyperphosphatemia is a major problem in these patients with advanced stage of CKD. Calcium carbonate became the most widely used phosphate binders ; however, increasing evidence now suggests that prolonged use of these agents increases the total body calcium load, induces adynamic bone, and potentially increases the risk of cardiovascular and soft tissue calcification. Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium-free, and metal-free. To date, this agent has been shown to effectively control serum phosphorus levels in patients with CKD. It may also attenuate coronary and aortic calcification and has a number of other beneficial effects on lipid metabolism and inflammation among others.

In 1960s and 1970s when hemodialysis therapy was started in Japan, calcium carbonate was used as a phosphate binder and as the purpose of calcium supplement. Aluminum preparations were widely used in Japan, Europe and United states since the end of 1970s, when these drugs were reported as a strong phosphate binder. After that, some adverse effects such as encephalopathy and bone lesions attributed to Aluminum administration have become serious problems in dialysis patients. As a result, Aluminum administration was prohibited in 1992 in Japan. Oral vitamin D pulse therapy was developed in 1990s as a treatment for secondary hyperparathyroidism in Japan, hypercalcemia have been occurred easily by combination use of vitamin D preparations and calcium carbonate. Since the 2000s, various complications, such as ectopic calcifications, cardiovascular diseases, and reduced life expectancy, which are associated with hypercalcemia and hyperphosphatemia have been clarified. Therefore, sevelamer hydrochrolide, that is non calcium phosphate binder, became available from 2003. Moreover, Lanthanum carbonate, that is another type of non calcium phosphate binder, was effective in Europe and United States, and also developing in Japan. However, there are not any phosphate binders which solved all clinical problems such as phosphate adsorptive power, digestive symptoms, and organ accumulation.

Recently, it is evident that sevelamer hydrochloride is superior to calcium carbonate in the anti-phosphorus therapy for the dialysis patients, from the viewpoints of vascular calcification and mortality. The efficacy of sevelamer hydrochloride was also suggested in predialysis patients. Although, in Japan, calcium carbonate, but not sevelamer, is only approved to the treatment in predialysis patients. It should be discussed about lanthanum carbonate. In this review, the management of phosphorus and the administration of phosphate binder in predialysis patients are extrapolated.

Controlling serum phosphorus levels in patients with chronic kidney disease is crucial. Since hyperphosphatemia is an established risk factor for not only secondary hyperparathyroidism, but also cardiovascular mortality in these patients, the adequate control of serum phosphorus is necessary. The target levels of serum phosphorus, however, are not consistently being met. To achieve better control of serum phosphorus levels, some novel phosphate binders, which do not contain calcium or metal, have been developed. In this manuscript we discuss some novel phosphate binders, which are now in clinical trials.

It has become clear that hyperphosphatemia is the major risk factor on the patients' survival undergoing regular renal replacement therapy. One of the mechanism of this impact on survival is ectopic calcification like vascular calcification. The standard therapy for hyperphosphatemia is phosphate removal by renal replacement therapy. However, since the amount of phosphate removal with today's hemodialysis procedure is not enough, the phosphate binder as depressant of phosphate absorption is still essential. Aluminum compound had been prohibited from 1992 due to serious adverse effect like aluminum encephalopathy and osteomalacia.Calcium carbonate and sevelamer hydrochloride are common phosphate binder. The combination therapy of both phosphate binders is recommended to avoid involvement in adverse effects of the both drugs. Lanthanum carbonate is developing compound as a new and powerful phosphate binder. It is expected as a new non-calcium and non-aluminum phosphate binder with powerful phosphate binding effect. However, the adverse effect of the Lanthanum carbonate is still obscure. Further investigation is acquired.

Chronic kidney disease (CKD) patients are belonging to high risk patients to atherosclerosis with vascular calcification. These patients are well recognized advanced arteriosclerosis with vascular medial calcification, with high risk of cardiovascular death. With basic investigated results, the mechanism of vascular calcification is making clear. A lot of various factors which participate in calcification have been specified. Especially, in long term dialysis patients, the very high grade vascular calcification with advanced atherosclerosis is common with calcium/phosphate/PTH and skeletal problem. This CKD related metabolic bone disorder (CKD-MBD) highly induced and progressed vascular calcification. Participates in vascular calcification. It is extremely important in order to prevent vascular calcification to manage serum phosphorus, serum calcium and parathyroid function within the suitable range. In addition, hyperphosphatemia is becoming the powerful risk factor for patients' survival. The new powerful phosphate binder is developing. The beneficial effect of the new agent on patients' survival is now focused.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) issued "Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease", in which it is recommended that the level of intact parathyroid hormone (i-PTH) should be kept at 150 - 300 pg/mL, the serum phosphorus (P) level at 3.5 - 5.5 mg/dL, and the serum calcium (Ca) level within the normal range of laboratory values (8.4 - 9.5 mg/mL, as close to the lower limit as possible). In developing these guidelines, the K/DOQI apparently considered the recently established fact that control of Ca, P and PTH influences not only the development of bone lesions but also patient prognostic factors such as arteriosclerosis, ectopic calcification, and cardiovascular complications, as well as the development of various vitamin D products and analogues and new P adsorbents. The Japanese guidelines also emphasize the control of P and Ca, rather than PTH. Therefore Phosphorus control is a primary goal in the care of patients with end-stage renal disease. We inspect the relationship between Vascular calcification and Sevelamer HCl, a non-aluminium, non-calcium, non-absorbed phosphate binder.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic kidney disease (CKD). Rats were fed a diet containing adenine for 4 weeks to establish CKD. Animals were then offered a diet containing sevelamer hydrochloride (sevelamer) or a normal diet for alternating 2 week periods over 8 weeks. Adenine-treated rats showed marked elevations of serum phosphorus, PTH and FGF23 levels associated with parathyroid hyperplasia and aortic calcification. Serum phosphorus, PTH and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, intermittent treatment with sevelamer successfully inhibited parathyroid hyperplasia and aortic calcification. In conclusion, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CKD. Setting up a period of reduced serum phosphorus levels, even if it is intermittent, is worthwhile for the inhibition of the development of parathyroid hyperplasia and aortic calcification.

When sevelamer hydrochloride is used as a phosphate binder instead of the more common calcium carbonate, the PTH rises. This has been observed in many cases and makes it more difficult for practical use. However, considering the calcium load, the excessive dosing of calcium carbonate must be avoided. With that in mind, we divided the i-PTH in groups of 100 pg/mL and tested the changes in i-PTH value, P value, the adjusted Ca value, and the product of Ca and P before and after a dosage of sevelamer hydrochloride. When the average i-PTH was under 100mg/mL 6 months before dosing, the sevelamer hydrochloride single dosage group showed an early rise in i-PTH after dosing, maintaining a higher level than the calcium carbonate combined dosage group. Therefore, it was concluded that the use of sevelamer hydrochloride alone as a phosphate binder is best. On the other hand, the group with an average i-PTH over 100 pg/mL 6 months before dosing showed a rise of i-PTH that went over the K/DOQI guideline with a single dosing of sevelamer hydrochloride. Therefore, we concluded that using both sevelamer hydrochloride and calcium carbonate for phosphate binder is best.

The aim of this study was to examine the therapeutic effect of hypocalcemic stimulation caused by sevelamer hydrochloride (SH) administration on adynamic bone disease (ABD). The subjects were 28 maintenance hemodialysis (HD) patients who had remained in ABD state in spite of no administration of vitamin D(3) since HD induction (15 males and 13 females;12 diabetic patients and 16 non-diabetic patients). The mean age was 61.8+/-9.5 years and the mean HD duration was 5.5+/-3.9 years. The calcium concentration in the dialysate was 3.0 mEq/L. We made the final daily dose of SH after two months the same as the first daily dose of calcium carbonate (CC) in the following manner. At first we administered only CC at breakfast and lunch and SH at supper. And for the next two weeks we administered CC at breakfast and SH at lunch and supper. And for the final two weeks we administered only SH. After that we increased the dose of SH as much as possible. We evaluated the therapeutic effect of the above treatment on ABD using intact-osteocalcin (iOC) [Teijin. Tokyo] as a marker before and 6, 12 months after the beginning of the replacement. If iOC Ievel of 30 to 70 ng/mL showed normal tumover bone (NTB), 5 cases (17.9%) changed into NTB in 6 months. 9 cases (32.1%) changed into NTB in 12 months and one case (3.6%) changed into ostitis fibrosa in 12 months. It is thought that SH is effective for the treatment of ABD but we have to be careful for ostitis fibrosa.

146 hemodialysis (HD) patients with secondary hyperparathyroidism (2 degrees HPT) were studied about the therapeutic effects of phosphate binders. We divided these patients into four groups; Group I: 59 patients treated with CaCO(3) (1.5-6.0 g/day), Group II: 42 cases with sevelamer hydrochloride (0.75-9.0 g/day), Group III: 30 with both CaCO(3) and sevelamer, Group IV: 15 with both CaCO(3) and cholestimide (1.5-6.0 g/day). These patients were prescribed several phosphate binders for at least 18 months. The serum levels of P, albumin-corrected Ca (Ca), Ca x P product and intact parathyroid hormone (iPTH) were serially determined. In Group I and IV, these four parameters showed no significant difference between at before administration and at after 1, 3, 6 and 12 months. In Group II, the values of iPTH, Ca and Ca x P product between at before sevelamer administration and at after 9 months were 199.43+/-94.40 vs 159.86+/-96.03 pg/mL (p<0.05), 9.48+/-1.12 vs 9.01+/-1.00 mg/dL (p<0.05) and 62.72+/-19.62 vs 50.44+/-25.97 mg(2)/dL(2) (p<0.05), respectively. In Group III, P showed significant decrease from 7.16+/-1.33 to 6.72+/-1.69 mg/dL (p<0.05) between at the time of adding sevelamer to CaCO(3) and at after nine months. These results indicate that sevelamer plays an excellent role in the treatment of 2 degrees HPT mainly by controlling Ca level and the combination therapy with CaCO(3) is useful for improvement of P level in patients undergoing HD.

It has been about 18 months after the commercial release of sevelamer hydrochloride. I examined the phosphorus management in patient with hemodialysis with the use sevelamer hydrochloride. The phosphorus reduction of sevelamer hydrochloride was weaker than the precipitated calcium carbonate. Patients on artificial dialysis must undergo dietary therapy for the sevelamer hydrochloride to be effective. However, by switching from precipitated calcium carbonate to sevelamer hydrochloride, the calcium level dropped, and as a result the intact PTH rose. It was possible to subdue the rise of intact PTH with vitamin D. The usefulness of vitamin D dramatically increased with the decrease and the eventual cancellation of precipitated calcium carbonate. Furthermore, the calcium load lightened and the product of calcium and phosphorus decreased. At this point, I do not expect substantial phosphorus reduction from sevelamer hydrochloride. It must be recognized that the basis of phosphorus management is proper diet. Only with that can sevelamer hydrochloride be used to its fullest potential.

About a dialysis patient's calcium-phosphate (Ca.P) metabolism, in general good control is obtained by use of sevelamer hydrochloride. As for this, what is significantly depended on not only lower P concentration but also lower Ca concentration by the change to sevelamer hydrochloride from calcium carbonate. However, by one side, much rises of i-PTH are observed by most patients with change to sevelamer hydrochloride. In this examination, Deltai-PTH was intentionally correlated with Delta calcium concentration but there was no correlation in i-PTH and Ca concentration.

In many hemodialysis patients at our hospital on May 2003, serum calcium levels were higher and intact PTH levels were lower than the target level of the K/DOQI guidelines. We could decrease doses of calcium-based phosphate binders by using sevelamer hydrochloride, and that could lower the level of calcium and raise the level of intact PTH. The number of patients who satisfy all the targets for calcium, phosphate, Ca x P and int-PTH, increased from 1.7% to 14.7% as a result of diet therapy and a change in their dose of medicine. It is natural that diet greatly influences on the control of calcium and phosphate, but if the period of hemodialysis is longer or there is swelling of the parathyroid, both diet therapy and medical therapy become more important for hemodialysis patients.

In patients with chronic renal insufficiency and dialysis, phosphate retention is a major factor in the development of vascular calcification. Prevention of phosphate retention with dietary and pharmacological means may prevent vascular calcification. Current therapy for hyperphosphatemia includes the administration of phosphate binders such as calcium carbonate (or calcium acetate), ammonium-based compounds, and phosphate-binding polymers (Renagel; sevelamer hydrochloride). However, it is difficult to administrate present phosphate binders to patients because of hypocalcaemia, outright toxicity, and constipation as its side effect. It is needed to development new drugs having fewer side effects and better compliance.

The recent global breakthrough in the field of renal osteodystrophy is the inhibitory effect of sevelamer hydrochloride on the progression of coronary artery calcification, which was revealed with EBCT (Electron beam computed tomography) 1) approximately 3). It has been found that the degree of coronary artery calcification assessed with EBCT is proportional to the mortality risk by the coronary artery stenosis and by myocardial infarction in non-hemodialysis patients 4) approximately 10). In 2004 in Japan Matsuoka and Iseki et al showed for the first time in the world that coronary artery calcification assessed by EBCT was correlated with mortality 11). In Japan, however, it is difficult to administer sevelamer hydrochloride to many patients because of constipation as its side effect. Its prescription rate is 26.8% and its single administration rate is only 15.4% 12). We explained fully to the patients that sevelamer hydrochloride seldom caused coronary artery calcification. And we used sorbitol, an osmotic purgatives, with sevelamer hydrochloride. Moreover, we gradually replaced calcium carbonate with sevelamer hydrochloride in supper at first. With protocol above, we succeeded in having 86.7% of the patients take sevelamer hydrochloride 12). We think that it is important to increase the intake rate of sevelamer hydrochloride in order to prevent coronary artery calcification and to aim at the long survival of the patients.

Newly developed sevelamer hydrochlorid (Sev-HCl) has been recognized to show the effective control of the hyperphosphatemia in chronic renal failure patients, without elevation of serum Ca, Mg, and Al as well. Then, Sev-HCl has been expected to evolute the vitamin D treatment, and to reduce the ectopic calcifications through lowering Ca x P products. Although, relatively high frequent abdominal adverse effects in Sev-HCl treatment were reported, including life-threatening bowel occlusions or bowel perforations. It is important to use the appropriate dose of Sev-HCl avoiding the abdominal adverse effects.

The pathogenesis of adynamic bone disease (ABD) attributes to calcium overload, active vitamin D (VD) metabolism, increase in inactive PTH (parathyroid hormone) fragments, or derangement of bone metabolism regulation factors. In particular, increased Ca overload plays a critical role in the development of ABD. Thus, alleviated Ca load by sevelamer hydrochloride and appropriate VD administration could be effective on not only prevention, and also treatment of ABD.

Sevelamer hydrochloride is a non-absorbed calcium- and metal-free phosphate binder that lowers the serum phosphorus levels in hemodialysis patients. Sevelamer contains multiple amines, which are partially protonated and interact with phosphate molecules through ionic and hydrogen bonding. We show the in vitro phosphate binding assay data and the efficacy of sevelamer to lower the serum phosphorus and calcium phosphorus product in several animal models. Furthermore, we indicate the vivid data that sevelamer prevented the ectopic calcification of aorta in adenine induced renal failure model, which represent severe hyperphosphatemia and the related dialysis complications.

Coronary artery calcification (CAC), observed in most end stage renal disease (ESRD) patients, has been reported to influence mortality and complications of cardiovascular diseases. Depend on the these reports, K/DOQI (Kidney Disease Outcomes Quality Initiative) guideline recommended to control serum Ca and phosphorus levels strictly in ESRD patients, in order to inhibit the progression of CAC. And then, we have been able to use new phosphate binder, sevelamer which dose not contain calcium and will able to use calcimimetics for secondary hyperparathyroidism as soon. Now, we should evaluate the diseases of bone as well as cardiovascular diseases according to the change of paradigms for renal osteodystrophy. It is undoubted that imaging methods play a main role on the management of CAC and coronary stenosis in end stage renal failure patients. Multidetector-row CT (MDCT) is a most useful imaging method, which has high temporal resolution and high spatial resolution. We may obtain adequate image quality for diagnosis and evaluate in 26 cases (87%), except for 4 cases not evaluated due to severe calcification. Therefore, this study suggested that 16-row MSCT is useful as a screening test for coronary angiography (CAG) even in dialysis patients.

Hyperparathyroidism, renal osteodystrophy and ectopic calcification, caused by hypocalcemia and hyperphosphatemia, are important complication in renal dysfunction, especially in end stage renal disease. Because it is the reason for reducing the survival rate and quality of life in these patients, it is important to control them from early stage in renal dysfunction. K/DOQI (kidney disease outcomes quality initiative) guideline shows us the recommended practical level and its account. It may be helpful for our daily clinical work.

Vascular calcification is clinically important, because it predicts a higher risk of cardiovascular event. Its pathogenesis involve atherosclerosis and regulated by mechanism which like bone metabolism. In dialysis patients, there is excess oxidative stress, shortage of scavenger, metabolic abnormality of calcium and phosphate. These factors may accelerate vascular calcification in dialysis patient. K/DOQI guideline shows the therapeutic strategy for calcium and phosphate metabolic abnormality. It is expected more progression in therapy for vascular calcification.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) provides evidence based clinical practice guidelines developed for all phases of kidney disease and related complications, from diagnosis to monitoring and management. Bone disease sets in during the early stages of Chronic Kidney Disease (CKD). Bone disease is observed in almost patients with chronic renal failure and after renal transplantation. Hyperparathyroid (high turnover) bone disease in patients with chronic renal failure is found most frequently followed by mixed osteodystrophy, low-turn over bone disease, and osteomalasia. Ninety to one hundred percent of kidney transplant patients have histological evidence of osteodystrophy and osteopenia (reduction of bone mass) following renal transplantation. Furthermore, osteoporosis is also appeared in many renal transplant recipients. After renal transplantation, renal osteodystrophy generally improves but bone mineral density (BMD) often worsens. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and carefully effective therapies might be reduced the morbidity associated with these common problems.

Management of hyperphosphatemia in hemodialysis patients is very important to prevent progress of renal hyperparathyroidism or ectopic calcification. Sevelamer hydrochloride is a Ca and Al free phosphate binder, and reduces serum phosphorus level, without any influence on serum Ca level, and Ca-P products. This compound is expected to reduce the incidence of arterial calcification, and improve the QOL (quality of life) of hemodialysis patients.

Recently "K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease" was published. It consists of sixteen precise guidelines which cover the wide range of this field. It is expected that these guidelines contribute ESRD treatment in Japan in spite of some differences in medical practice for dialysis therapy between Japan and the United States. This article briefly summarizes the outlines of these guidelines.