Uncontrolled Hyperphosphatemia Research Articles

The role of ferric citrate in a sample of Iraqi patients on hemodialysis- A randomized controlled clinical trial

Background: Uncontrolled hyperphosphatemia is the main difficulty facing staff treating patients with end-stage renal disease on hemodialysis. Sevelamer and calcium-containing phosphate binders have been associated with cost burden and tissue calcification, respectively. Therefore, the current trial was targeted to investigate the efficacy of a new phosphate binder, ferric citrate, in a sample of Iraqi patients with end-stage renal disease on hemodialysis. Keywords: Ferric citrate, Hemodialysis Phosphate binder

Factors Associated with Compliance to Low Phosphate Diets in Hemodialysis Patients with Uncontrolled Hyperphosphatemia

Factors Associated with Compliance to Low Phosphate Diets in Hemodialysis Patients with Uncontrolled Hyperphosphatemia

MO1034PHOSPHATE EQUIVALENT (PEQ) EDUCATION SYSTEM: AN EFFICIENT SELF-ADJUSTMENT PHOSPHATE BINDER DOSAGE TOOL IN DIALYSIS PATIENTS

Abstract Background and Aims Hyperphosphatemia is common in end-stage renal disease (ESRD) because of impaired renal phosphate excretion and is treated by dietary measures, dialysis techniques and the use of phosphate binder medication. It is one of the most important cardiovascular risk factors for dialysis patients. Our goal was to involve dialysis patients in the achievement of phosphate targets by self-adjusting the dose of Phosphate Binders (PB) on a meal-to-meal basis, according to the individual dietary P intake Method We conducted an interventional prospective single-arm study with a pre-post design. The inclusion criteria were patients with ESRD who had been receiving dialysis for more than three months, with dialysis schedule for four hours per session, three times per week, and who were older than 18 years of age. The primary endpoints of the study were the number of patients who reached the goal of serum phosphate before and after the training program and the weekly mean serum phosphate levels evaluated after the intervention period and compare them with the pre-intervention baseline levels. The secondary end-point was the burden of PB daily. All patients were trained in a self-administer PB program. A self-adjusted PB dose card was developed based on the phosphate food content list published by the National Technical University of Athens. The aim was to allow patients to immediately calculate the iP content of any food they consume easily. Phosphate Equivalent (PEQ) was defined as the weight of phosphorus having the same phosphate impact as a given weight of food. One PEQ corresponded in 100 mg of inorganic phosphorous and to one tablet of PB (one tablet of 800 mg of sevelamer). After 4 weeks (weeks 1-4) of washout from previous phosphate binders, eligible patients with serum phosphorus concentrations ≥ 6 mg/dl were included in the study. All patients received standard dietary phosphate counseling and a fixed dosing regimen of sevelamer PB was prescribed according to KDIGO and dialysis unit protocols for eight weeks (weeks 5-12 – pre-intervention period) In the 13th week, patients were asked to practice the self-administer PB program for eight more weeks. Results A total of 97 patients were screened for the study. 21 patients were excluded. 74 patients completed the study. The percentage of patients with uncontrolled phosphate levels reduced from 56.76% (42 out of 74) to 36.48 % (27 out of 74) in the post-intervention period. Of 9 patients who initially had a serum phosphorus level ≥9 mg/dl, 8 were reverted to phosphorus levels < 6 mg/dl at the end of the PEQ intervention period. There was a significant reduction of phosphate levels (prePEQ 7.42 ± 1.43 mg/dl vs. postPEQ 5.59 ± 1.82 mg/dL, p=0.036) and Ca × P levels (prePEQ: 67.1 ± 11.5 mg2/dL2; postPEQ: 51.9 ± 13.4 mg2/dL2, p=0.021) after patient education. There was a non-significant increase on serum calcium (pre PEQ: 8.13 ± 1.18 mg/dL; post PEQ: 8.56 ± 0.83mg/dL, p=0.515) and iPTH (prePEQ: 411 ± 376 pg/mL; postPEQ: 381 ± 321 pg/mL,p=0.13) Conclusion Our work shows that providing the patients with a relatively simple tool about the use of phosphate binders as PEQ is, we had a positive effect on the dialysis patients’ knowledge about the use of PB, phosphate content of their meals, and increase their sense of the necessity of the treatment and it was proved more effective than the standard fixed dose method. Using the PEQ education system was rewarding in an additional 20% of the patients with previous uncontrolled hyperphosphatemia. The PEQ education system is an efficient self-adjustment phosphate binder dosage tool in dialysis patients in reducing the serum phosphate level in our hemodialysis patients.

Estimating hospital inpatient cost-savings with sucroferric oxyhydroxide in patients on chronic hemodialysis in five European countries: a cost analysis

Aims Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. Materials and methods All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. Results Annual inpatient cost-savings per patient in the mSO group versus the dSO group were €1,201, €2,097, €2,059, €1,512, and €3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were €327, €1,585, €1,022, €1,100, and €2,204, respectively. Limitations Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. Conclusion SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.

Sucroferric Oxyhydroxide as Part of Combination Phosphate Binder Therapy among Hemodialysis Patients.

Combination therapy with multiple phosphate binders is prescribed to reduce elevated serum phosphorus (sP) concentrations among patients on maintenance hemodialysis. Sucroferric oxyhydroxide (SO), an iron-based phosphate binder, has demonstrated efficacy at reducing sP while also being associated with a low pill burden. Whereas the effects of SO monotherapy have been well characterized in clinical trials and observational cohorts, little is known about the effects of SO-containing combination therapy. Patients on hemodialysis (N=234) at Fresenius Kidney Care (FKC) who received ≥120 days of uninterrupted phosphate binder combination therapy with SO were included in this retrospective study. Patient data were censored after SO discontinuation, end of care at FKC, or completion of 12 months of follow-up. Quarterly (Q) changes in phosphate binder pill burden, mean sP, and proportion of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI)-recommended sP levels (≤5.5 mg/dl) were compared between baseline (-Q1) and follow-up (Q1-Q4). Phosphate binder combination therapy with SO was associated with significant increase in the proportion of patients with sP ≤5.5 mg/dl (from 19% at baseline to up to 40% at follow-up; P<0.001) and reduction in sP at all postbaseline time points (from 6.7 mg/dl to 6.2-6.3 mg/dl; P<0.001). Patients on calcium acetate (N=54) and sevelamer (N=94) who added SO therapy at follow-up resulted in a ≥250% increase in patients achieving sP ≤5.5 mg/dl (all P<0.001). Whereas mean phosphate binder pill burden increased with initiation of phosphate binder combination therapy with SO (15.8 pills/d at Q1 versus 12.3 pills/d at -Q1), continued use of SO was associated with down-titration of non-SO phosphate binders such that, by Q4, mean total PB pill burden reduced to 12.3 pills/d. For patients on hemodialysis with uncontrolled hyperphosphatemia, combination therapy with SO may allow for sustained improvements in sP control without adversely affecting phosphate binder pill burden.

SAT-102 ECTOPIC MEDIASTINAL PARATHYROID CARCINOMA ACCOMPANYING BY PARATHYROID HYPERPLASIA IN A HEMODIALYTIC PATIENT

Parathyroid carcinoma is a rare cancer, and the development under secondary hyperparathyroidism is also clinically infrequent. The diagnosis of parathyroid carcinoma under secondary hyperparathyroidism may be difficult due to a radiological similarity between parathyroid carcinoma and adenoma. Moreover, if hemodiaytic patients only show parathyroid hyperplasia without parathyroid adenomatous change by uncontrolled hyperphosphatemia, maligant change of parathyroid gland may be rarely developed. We report an interesting case showing an ectopic mediastinal parathyroid carcinoma related with uncontrolled secondary hyperparathyroidism and parathyroid hyperplasia in patient with end-stage renal disease (ESRD) undergoing hemodialysis. N/A (This abstract is a case report) A 30-year-old man on maintenance hemodialysis due to chronic rejection of transplanted kidney showed a recurrently high level of serum intact parathyroid hormone (iPTH) without remarkable decreases despites of intensive medications including intravenous calcitriol and lanthanum carbonate. Parathyroid scan revealed parathyroid hyperplasia in the both upper portions of thyroid. Ultrasound did not show extrathyroidal nodular lesions. Firstly, simultaneous use of cinacalcet and calcitriol was implemented, and we performed a follow-up scan due to persistently uncontrolled hyperparathyroidism and hypercalcemia. When compared with prior parathyroid scan, it showed more increased parathyroid hyperplasia in the same area, and new hot lesions in left lower portion of thyroid and right upper paratracheal area in mediastinum were newly shown. Computed tomography (CT) of neck showed multiple nodular lesions in the mediastinal area, compatible with ectopic parathyroid adenoma, along with hyperplasia on both upper and left lower parathyroid glands. Firstly, we referred to thoracic surgery for the mediastinal mass. The preoperative laboratory results were as follows: serum calcium, 10.4 mg/dL; serum iPTH, 1150 pg/mL. The mediastinal masses with diameters of less than 2.2 cm were removed and histologically compatible with parathyroid carcinoma. Serum iPTH did not postoperatively decrease, but serum calcium decreased. We performed a 18F-fluorodeoxyglucose positron-emission tomography-CT scan for parathyroid gland and distant metastases of parathyroid carcinoma. It revealed no locoregional and distant metastases of parathyroid carcinoma except remained parathyroid hyperplasia. We recommended total thyroidectomy immediately due to uncontrolled secondary hyperparathyroidism. After one month, the patient was performed total thyroidectomy and serum iPTH level was normalized after the operation. The pathologic results after total thyroidectomy showed only parathyroid hyperplasia without adenomatous changes and it also revealed no locoregional metastatic lesion of parathyroid carcinoma. A diagnosis of parathyroid carcinoma without a confirmative surgery is difficult particularly in uncontrolled secondary hyperparathyroidism without parathyroid adenoma. Moreover, an ectopic mediastinal parathyroid carcinoma under same condition may be easily underdiagnosed. Thus, dialytic patients with refractory secondary hyperparathyroidism irregardless of existence of parathyroid adenoma should perform a radiologically close follow-up, even if the first scan show only parathyroid hyperplasia.

Phosphates in medications: Impact on dialysispatients .

Maintaining phosphorus balance in in-center hemodialysis (ICHD) patients is problematic despite recommended dietary restriction, dialysis, and phosphate binder use. Rarely is P content in prescribed medications considered, but this source should raise concern. Data was obtained from the Fresenius Kidney Care (FKC) electronic data warehouse Knowledge Center and MedReview-eRx accessed Surescripts, housing > 80% of US-filled prescriptions. Adult FKC ICHD patients prescribed ≥ 1 medication in the MedReview-eRx database were analyzed (695,759 prescriptions). Information collected included medication dose, dose unit, dose timing, strength, start and stop dates, refills, demographic information, admission history, and modality type. Numbers of patients, prescriptions by individual medication, and drug class were then analyzed. Medications prescribed > 100 times were reported. Median doses/day (number of tablets) were calculated for each medication (open order on randomly selected day). Phosphate content of medications taken in FKC clinics was assessed using routinely used pharmacology references, and potential resulting phosphate and pill burden were also calculated. The top five prescribed drug classes in FKC dialysis patients were calcium-channel blockers (22%), proton pump inhibitors (PPIs; 18%), acetaminophen-opioid (AO; 13%), angiotensin-converting enzyme inhibitors (ACEi; 10%), and α2-agonists (9%). The maximum phosphate added for different medications varied by manufacturer. For instance, at median daily doses, phosphate contributions from the top five medications prescribed were 112 mg for amlodipine, 116.2 mg from lisinopril, 6.7 mg from clonidine, 0 mg from acetaminophen, and 200 mg for omeprazole. Prescribing these together could increase the daily phosphate load by 428 mg, forcing the patient to exceed the recommended daily intake (RDI) with food and drink. Phosphate content in medications prescribed to HD patients can substantially contribute to the daily phosphate load and, in combination, may even exceed the daily recommended dietary phosphate intake. Healthcare providers should monitor all medications containing phosphate prescribed in order to minimize risk of uncontrolled hyperphosphatemia and poor adherence.

Additional benefit of dietitian involvement in dialysis staffs-led diet education on uncontrolled hyperphosphatemia in hemodialysis patients.

Sustained adherence to dietary phosphorus (P) restriction recommendations among hemodialysis patients is questionable. The aim of this study was to evaluate the effectiveness of additional diet education delivered by a dietitian on the control of hyperphosphatemia. We conducted an 8-month prospective observational study in hemodialysis patients who had uncontrolled hyperphosphatemia. In the first half of the study (experimental) period, the dialysis nurses and physicians provided the routine dietetic education with the control group (n=31), while the experimental group (n=30) received the routine dietetic education plus an additional diet education delivered by dietitians. Both groups received the routine dietetic education in the rest of the study period to test whether the improvement of serum P level was sustained. The primary outcomes were changes in serum P level. At baseline, there was no significant difference in serum P levels between groups (P=0.27). In the experimental period, monthly serum P levels decreased significantly in both groups (P<0.001) and the magnitudes of reduction were 1.81±1.46 and 0.94±1.33mg/dL in the experimental and control groups, respectively (P=0.02), at the end. The experimental group maintained such improvement for one more month (P=0.02), but faded out over time. Renal diet education guided either by dietitians plus dialysis staffs or dialysis staffs alone reduces serum P level and dietitian-guided diet education provides an additional benefit on controlling hyperphosphatemia in hemodialysis patients.

Hyperphosphatemia is associated with patency loss of arteriovenous fistula after 1 year of hemodialysis

BackgroundThe patency of arteriovenous access is important for stable and effective hemodialysis, and long-term technical survival is best achieved with a native arteriovenous fistula (AVF). However, maintaining AVF patency remains a challenge. This study was designed to determine the independent prognostic factors for AVF patency according to hemodialysis duration. MethodsThe primary study end point was unassisted patency of the AVF, which was defined as the time from the first fistula surgery to the first AVF failure. AVF failure was defined as an event that required percutaneous intervention or surgery to revise or replace the fistula, which occurred at least 2 months after fistula formation. ResultsWe enrolled 478 patients with a mean age of 55.5±14.0 years, and mean duration of dialysis was 2.5±2.1 years. There were 109 cases (22.8%) of AVF failure. The factors related to AVF patency differed according to hemodialysis duration. Using a Cox-adjusted model, we observed a significant correlation between the incidence of AVF failure and diabetes within the initial 12 months of hemodialysis. Uncontrolled hyperphosphatemia (mean serum phosphorus>5.5mg/dL during hemodialysis) was associated with patency loss of AVF after 1 year of hemodialysis. ConclusionVarious factors were associated with the development of patency loss of AVF as hemodialysis duration differed, and a preventive role of hyperphosphatemia control in AVF survival needs further clinical study.

Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia.

Lanthanum carbonate is a non-calcium phosphate binder that is effective for the treatment of hyperphosphatemia. However, it is unknown whether treatment with lanthanum affects survival. We retrospectively collected data on maintenance hemodialysis patients at 22 facilities (n = 2292) beginning in December 2008, a time point immediately prior to the commercial availability of lanthanum in Japan. We compared 3-year all-cause mortality among patients who initiated lanthanum (n = 560) and those who were not treated with lanthanum during the study period (n = 560) matched by the propensity score of receiving lanthanum. Several sensitivity analyses were performed to test the robustness of the primary analysis. After the market introduction of lanthanum, the percentage of patients receiving the binder increased gradually to 27%. In the propensity score-matched analysis, the mortality rate for the lanthanum group was not significantly lower than the non-lanthanum group [hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.47-1.09). However, stratification by serum phosphorus disclosed significant survival benefit of lanthanum for patients with serum phosphorus >6.0 mg/dL (HR, 0.52; 95% CI, 0.28-0.95), but not in patients with serum phosphorus ≤6.0 mg/dL (HR, 1.00; 95% CI, 0.55-1.84). The survival benefit of lanthanum in patients with serum phosphorus >6.0 mg/dL was consistent across subgroups and robust in different analytical approaches. Treatment with lanthanum was independently associated with a significant survival benefit in hemodialysis patients with inadequately controlled hyperphosphatemia. Further studies are required to confirm these findings.

Uremic Tumoral Calcinosis in Patients on Peritoneal Dialysis: Clinical, Radiologic, and Laboratory Features

Uremic tumoral calcinosis (UTC) has been analyzed in uremic patients on hemodialysis, but little is known about UTC in peritoneal dialysis (PD). In this study, we aimed to characterize UTC in uremic patients on PD. We retrospectively reviewed uremic patients on PD who developed UTC over a 9-year period. Clinical, radiologic, and laboratory features; treatments; and outcomes in those patients were assessed. One of the patients (case 7) is described as a case example. The study enrolled 7 patients with a mean age of 41 years. Mean time from PD to UTC was 45.3 months. All patients were anuric but adequately dialyzed. Cardinal symptoms were local tenderness and limited range of joint motion. Lesions were mostly multifocal (n=6) and predominantly involved shoulders, hands, feet, hips, and wrists. Metatarsophalangeal joint UTC was misdiagnosed as tophaceous gout in 2 patients. Main laboratory findings were hyperphosphatemia (7.9 ± 0.8 mg/dL), high Ca×P product [>65 mg(2)/dL(2) (range: 81.1 ± 11.5 mg(2)/dL(2))], secondary hyperparathyroidism (SHPT) with various levels of intact parathyroid hormone (iPTH: 592.2 ± 315.2 pg/mL; <250 pg/mL in 2 patients). Medical treatments for UTC included P restriction, non-Ca-based phosphate binders, and adequate dialysis with low-Ca dialysate, but all treatments were ineffective. Parathyroidectomy (n=3) can partially ameliorate UTC, but only 1 patient (case 7), who had extremely high iPTH (1085 pg/mL), manifested hungry bone syndrome (HBS) and had remarkable resolution of UTC. By contrast, in patients who underwent renal transplantation (n=3), UTC completely resolved by about 1 year after surgery. Uremic tumoral calcinosis develops in anuric PD patients with uncontrolled hyperphosphatemia; it is usually multifocal, occurring around the weight-bearing joints or overused smaller joints. Aggressive medical therapy alone is ineffective, and parathyroidectomy appears to be unsatisfactory except in the presence of severe SHPT with postoperative HBS.

Clinical Efficacy and Cost-Effectiveness of Lanthanum Carbonate as Second-Line Therapy in Hemodialysis Patients in Japan

Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined. We first conducted a multicenter, open-label, 16-week clinical trial to examine the effect of additive LC in 116 hemodialysis patients who had uncontrolled hyperphosphatemia with conventional phosphorus-lowering therapy alone. Based on these clinical data, a state transition model was developed to evaluate the benefits and costs associated with LC as second-line therapy. Reduced risks for cardiovascular morbidity and mortality among patients treated with LC arise through more of the population achieving the target phosphorus levels. Uncertainty was explored through sensitivity analysis. After 16 weeks of additive LC treatment, mean serum phosphorus levels decreased from 7.30 ± 0.90 to 5.71 ± 1.32 mg/dl, without significant changes in serum calcium or intact parathyroid hormone levels. A subsequent cost-effectiveness analysis showed that compared with conventional treatment, additive LC incurred an average additional lifetime cost of $22,054 per person and conferred an additional 0.632 quality-adjusted life years (QALYs). This resulted in an incremental cost-effectiveness ratio of $34,896 per QALY gained. Applying a cost-effectiveness threshold of $50,000 per QALY, a probabilistic sensitivity analysis showed that additive LC had a 97.4% probability of being cost-effective compared with conventional treatment. Our results indicate that the use of LC as second-line therapy would be cost-effective among hemodialysis patients with uncontrolled hyperphosphatemia in Japan.

Effect of Short-Term Low-Protein Diet Supplemented with Keto Acids on Hyperphosphatemia in Maintenance Hemodialysis Patients

Aim: To evaluate the effects of short-term restriction of dietary protein intake (DPI) supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis (MHD) patients. Methods: Forty MHD patients with uncontrolled hyperphosphatemia were randomized to either low DPI with keto acid-supplemented (sLP) or normal DPI (NP) group for 8 weeks. After 8 weeks, the sLP group was shifted to NP for another 8 weeks. Low-protein diet (LPD) was individualized with total caloric intake 30–35 kcal/kg/day, protein intake of 0.8 g/kg/day and phosphate intake of 500 mg/day. Keto acids were supplied in a dosage of 12 pills per day. Calcium phosphorous metabolism index and nutritional index (serum albumin, total protein, somatometric measurements, 3-day diaries and Mini-Nutritional Assessment score) were recorded. C-reactive protein, CO₂ combining power and Kt/V were measured to evaluate the inflammation, metabolic acidosis and dialysis adequacy, respectively. Results: Serum phosphorus level and calcium-phosphate product were significantly decreased at the end of the first 8 weeks in the sLP group compared to the basal value and the NP group (p < 0.001). No difference was observed in C-reactive protein, Kt/V and nutritional index, while CO₂ combining power was significantly higher at week 8 in the sLP group (p < 0.001). Conclusion: Short-term restriction of DPI supplemented with keto acids could decrease hyperphosphatemia and calcium-phosphate product, while keeping stable nutritional status among MHD patients.

Massive Soft Tissue Calcifications and Cinacalcet

A 37-yr-old man on long-term hemodialysis developed a relapse of secondary hyperparathyroidism after subtotal parathyroidectomy. Dialysis treatment adjustment and conventional medical therapies, involving noncalcium phosphate binders and active vitamin D sterols, proved ineffective. Painful and rapidly increasing tumor-like masses appeared over the second finger and the back of his right hand. Laboratory studies showed persistent serum levels of intact PTH of more than 1500 pg/ml and calcium-phosphate product of more than 100 mg/dl [recommended levels in dialysis patients, 150–300 pg/ml (16.5–33 pmol/liter) and 55 mg/dl, respectively] (1). A radiograph of the right hand revealed massive soft tissue swelling and calcifications (Fig. 1). Due to the patient’s disinclination for further surgical treatment, we decided to administer cinacalcet (2, 3), a calcimimetic agent, at doses of 30–60 mg/d, achieving a significant suppression of intact PTH (350 pg/ml) and calcium-phosphate product (60 mg/dl). After correction of the calcium-phosphate product, oral calcitriol and calcium acetate were administered. Six months later, a radiographic control showed the disappearance of the calcifications (Fig. 2). Massive soft tissue calcification is a feature of severe renal hyperparathyroidism and is due to chronic elevation of calciumphosphate product, resulting in the precipitation of calcium phosphate. The calcified masses should not be misdiagnosed as tumors and surgically excised, because they will recur unless the biochemical abnormalities are corrected (4). High serum calcium and phosphate levels may also cause disseminated calcification in the skin, joints, viscera, and arteries (calciphylaxis) resulting in painful ischemic necrosis of skin and gangrene, cardiac arrhythmias, and pulmonary failure. Uncontrolled hyperphosphatemia and progressive metastatic calcifications have always been indications for surgical parathyroidectomy (5). When conventional therapies have been exhausted, cinacalcet represents an exceptional therapeutic opportunity particularly for patients exposed to technical difficulties linked to a neck re-operation (3).

Novel cardiovascular risk factors in end-stage renal disease.

Traditional risk factors only in part explain the risk differential between the general population and the population of patients with chronic nephropathies. Uncontrolled hyperphosphatemia and high calcium phosphate product constitute risk factors for cardiovascular calcifications, cardiac ischemia, and adverse cardiovascular outcomes, yet inflammation may be an even more important trigger of vascular calcification than these metabolic derangements. Homocysteine predicts cardiovascular events in ESRD, but evidence that this sulfur amino acid is directly implicated in the high cardiovascular mortality of uremic patients is still lacking. It seems unlikely that Chlamydia pneumoniae is a major risk factor in dialysis patients because the association between anti-Chlamydia antibodies and incident cardiovascular events seems to depend largely on the confounding effect of some traditional risk factors. Oxidative stress and raised plasma concentration of asymmetric dimethylarginine (ADMA) are pervasive in ESRD, and high ADMA in these patients may be at least in part the expression of the high rate of generation of oxidants. ADMA per se seems responsible for a 52% increase in the risk of death and for a 34% increase in the risk of cardiovascular events in dialysis patients.

Overview of renal bone disease: Causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach: Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease

Divalent ions, metabolism abnormalities, and hyperparathyroid bone disease noted in patients with chronic kidney disease (CKD) develop early in the course of renal insufficiency. In the last two decades, therapy has focused mostly in treating the bone lesion as well as controlling the secondary hyperparathyroidism. However, recent large epidemiologic studies have highlighted the importance of both hyperphosphatemia and an increase in the calcium burden as major factors leading to the high mortality rate of end-stage renal disease (ESRD) patients [1–3]. Furthermore, a recent study strongly suggests the high mortality rate may be due to an increase in cardiac events [4]. In the present manuscript, the causes for the failure of the original therapeutic goals will be discussed first; the changing pattern in the bone lesions will be assessed second; and third, future therapeutic approaches will be explored, with special emphasis in early therapy and avoiding the cardiovascular abnormalities recently noted in CKD patients.

Association of inflammation and malnutrition with cardiac valve calcification in continuous ambulatory peritoneal dialysis patients.

Cardiac valve calcification (VC) has long been regarded as a consequence of aging and abnormal calcium-phosphate metabolism in uremic patients. In view of the recent recognition of association among inflammation, malnutrition, and atherosclerosis, the possible role of inflammation and malnutrition in VC was investigated. Inflammatory markers (including C-reactive protein [CRP], fibrinogen, and basal metabolic rate) and nutritional status (assessed using serum albumin, subjective global nutrition assessment, and handgrip strength) were examined, in addition to calcium phosphate parameters and other traditional cardiovascular risk factors, including gender, smoking habits, BP, and lipid profile, in relation to VC in 137 patients who were on continuous ambulatory peritoneal dialysis. Compared with patients with no VC, patients with VC not only were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients with VC versus 17% of patients with no VC were moderately to severely malnourished according to subjective global nutrition assessment (P = 0.05). Even after adjustment for patients' age, duration of continuous ambulatory peritoneal dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85; P = 0.01). The data suggest that VC not only is a passive degenerative process but also involves active inflammation, similar to that seen in atherosclerosis. The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further accelerates the progression of calcification. The data also indicate that VC and atherosclerosis should be considered as associated syndromes, sharing similar pathogenic mechanisms, namely active inflammation.

Hyperphosphatemia accelerates parathyroid cell proliferation and parathyroid hormone secretion in severe secondary parathyroid hyperplasia.

We studied the role of phosphorus retention in parathyroid cell proliferation and parathyroid hormone (PTH) oversecretion in severe secondary parathyroid hyperplasia. Mice transplanted with human parathyroid tissue from a patient who had undergone parathyroidectomy for severe secondary hyperparathyroidism were divided into four groups; each group was given a diet with a different phosphorus content (0.4, 0.7, 1.0, and 1.2%) to alter serum phosphorus concentrations. Histologic examinations of grafts by hematoxylin-eosin or by bromodeoxyuridine (BrdU) immunohistochemical staining were performed to assess parathyroid cell proliferation. Changes in serum phosphorus concentrations unidirectionally affected PTH secretion from the graft, because human PTH did not cross-react with mouse PTH. Serum phosphorus concentrations of 1.0P and 1.2P groups were significantly higher than those of 0.4P and 0.7P groups (p<0.05). Serum phosphorus concentrations were significantly correlated with the gradient of human PTH elevation with a coefficient of 0.48 and a p<0.05. Furthermore, serum phosphorus concentrations and the gradient of human PTH elevation were significantly higher in mice with BrdU-immunoreactive cells in the parathyroid graft than in mice without immunoreactive cells in the graft. These results indicate that uncontrolled hyperphosphatemia may accelerate the proliferation of parathyroid cells, exacerbating PTH oversecretion.

Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis

Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.