Higher Serum Phosphate Levels Research Articles

Serum phosphate and hip bone mineral density as additional factors for high vascular calcification scores in a community-dwelling: The São Paulo Ageing & Health Study (SPAH)

ObjectiveTo analyze the association between abdominal aortic calcification scores (AACS) and bone metabolism parameters in a well-characterized general population of older adults. BackgroundSeveral studies suggest a link between bone mineral metabolism disorders and vascular calcification; although only few of them analyze bone mineral density(BMD), laboratory bone markers and cardiovascular parameters at the same time and none were done in a miscegenated population. MethodsThis cross-sectional study included 815 subjects ≥65years old. The risk factors for osteoporosis and cardiovascular disease as well as a wide array of demographic and lifestyle characteristics were collected using a standardized questionnaire. BMD was measured by DXA. Kauppila's method was used to quantify the AAC score (AACS) by spine X-rays. Laboratory analyses were also performed. ResultsAAC was observed in 63.2% of subjects with a median AACS of 2 (IQR: 0–7). AACS were categorized in quartiles and the highest quartile of AACS (>7) were compared with the three lower quartiles of AACS (≤7). Logistic regression analysis was performed using parameters with statistical significance in the univariate analysis. The best logistic regression model revealed that AACS>7 was negatively associated with femoral neck BMD and positively associated with phosphorus, adjusted by age, current smoking, LDL, and arterial hypertension in the elderly community-dwelling population. ConclusionsWe identified that higher serum phosphate levels and lower hip BMD are independent bone variables that are associated with elevated vascular calcification scores, supporting the search for effective prevention and treatment strategies that may simultaneously reduce these modifiable risk factors in older subjects.

T.P.12 Dietary phosphate intake and exercise-induced stress induce severe muscle necrosis in adult mdx mice

Progressive muscle degeneration, ectopic calcification in skeletal muscle, and high serum phosphate levels are characteristic features of muscular dystrophy especially in mdx mice. However, the effects of dietary phosphate intake on ectopic calcification and muscle pathology are not well studied. We previously reported that increased dietary phosphate intake caused elevated serum phosphate (Pi) levels, severe ectopic calcification and reduced muscle function in mdx mice. In contrast, lowering phosphate intake ameliorated the pathogenesis of the mice. In this study, we examined the effects of dietary phosphate intake and exercise-induced stress on muscle pathology of 90days old mdx mice (adult mdx mice). Voluntary running on activity wheel (VR) increases physical activity and negatively affects muscle pathology of the mice. We found that 10days of VR exacerbated muscle degeneration, increased macrophage infiltration and increased ectopic calcification in limb muscles of high-phosphate fed adult mdx mice. Tibialis anterior (TA) muscle, which consists mostly of muscle fibers with central nuclei and minimal necrotic areas when the mice were kept in a normal cage, was the most affected muscle by VR. Since numerous muscle fibers were embryonic heavy chain positive, high-phosphate intake did not interfere with muscle regeneration but dramatically progressed muscle degeneration. Interestingly, exercise and low-phosphate intake had relatively few areas of group degeneration and no ectopic calcification in TA muscle of mdx mice. The muscle pathologies of the exercised and non-exercised mdx mice fed low-Pi diet were similar. Therefore we conclude that high dietary phosphate intake progresses the pathogenesis of muscular dystrophy, and lowering phosphate intake could increase resistance to exercise-induced damage.

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. Longitudinal. The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. Demographic, clinical, and biochemical parameters were recorded simultaneously. The Agatston score was measured again 3.5 or more years later. Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.

Choosing Not to Take Phosphate Binders: The Role of Dialysis Patients’ Medication Beliefs

Objective: Patients with end-stage renal disease (ESRD) receiving haemodialysis are at risk of cardiovascular disease and bone disorders related to high levels of serum phosphate (PO₄). Phosphate binders are an important treatment; however, non-adherence remains a significant issue. This study investigates whether patients’ beliefs about medicines predict intentional non-adherence to phosphate binders. Method: This was a cross-sectional study of ESRD patients (n = 76). Non-adherence was measured in two ways: (1) the self-report Medication Adherence Questionnaire (MAQ) and (2) 3-month average level of serum phosphate. The Beliefs about Medicines questionnaire was used to assess general and specific beliefs towards phosphate medicines. Results: Eleven (14.5% of 76) patients reported being intentionally non-adherent to phosphate binders. Patients’ beliefs that phosphate binders were less necessary were significantly associated with intentional self-reported non- adherence. Furthermore, patients with greater concerns about phosphate binders had higher serum phosphate levels. Conclusion: Assessing patient beliefs about medicines is a reliable indicator of intentional non-adherence to treatment with phosphate binders. These findings may help in identifying ways in which adherence rates to phosphate binders can be improved.

Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability

BackgroundDysregulaiton of phosphate homeostasis as occurs in chronic kidney disease is associated with cardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease. The molecular mechanisms by which high or low serum phosphate levels adversely affect cardiovascular function are poorly understood. The purpose of this study was to explore the mechanisms of endothelial dysfunction in the presence of non-physiologic phosphate levels.Methodology/Principal FindingsWe studied the effects of simulated hyper- and hypophosphatemia in human umbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C β2 (PKCβ2), reduced cell viability, and increased apoptosis. While simulated hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios, NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance.Conclusions/SignificanceThis is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and increased PKCβ2. Hyperphosphatemia also appears to reduce eNOS transcription via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the other hand, hypophosphatemia appears to activate these pathways. Our data provides the basis for further studies to elucidate the relationship between altered phosphate homeostasis and cardiovascular disease. As a corollary, our data suggests that the level of phosphate in the culture media, if not in the physiologic range, may inadvertently affect experimental results.

Association of Serum Phosphate Levels With Aortic Valve Sclerosis and Annular Calcification: The Cardiovascular Health Study

This study was conducted to evaluate mineral metabolism markers as potential risk factors for calcific aortic valve disease. Mineral metabolism disturbances are common among older people and may contribute to cardiac valvular calcification. Associations of serum mineral metabolism markers with cardiac valvular calcification have not been evaluated in a well-characterized general population of older adults. We measured serum levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D in 1,938 Cardiovascular Health Study participants who were free of clinical cardiovascular disease and who underwent echocardiographic measurements of aortic valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular calcification (AAC). We used logistic regression models to estimate associations of mineral metabolism markers with AVS, MAC, and AAC after adjustment for relevant confounding variables, including kidney function. The respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5 mg/dl higher serum phosphate concentration was associated with greater adjusted odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95% CI: 0.99 to 1.25, p = 0.05). In contrast, serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations were not associated with aortic or mitral calcification. Higher serum phosphate levels within the normal range were associated with valvular and annular calcification in a community-based cohort of older adults. Phosphate may be a novel risk factor for calcific aortic valve disease and warrants further study.

Brachial-ankle pulse wave velocity and rate of renal function decline and mortality in chronic kidney disease.

Increased arterial stiffness was reported to be associated with decreased estimated GFR (eGFR). Previous studies suggested that arterial stiffness might play a role in renal function progression in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether there was an independent association between brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, and renal function progression in CKD patients. This longitudinal study enrolled 145 patients with CKD stages 3 to 5. The baPWV was measured by using an ABI-form device. The change in renal function was estimated by eGFR slope. The study endpoints were defined as commencement of dialysis or death. After a stepwise multivariate analysis, the eGFR slope was positively associated with baseline eGFR and negatively associated with hypertension and baPWV (β=-0.165, P=0.033). Seventeen patients entering dialysis, and eight deaths were recorded. Multivariate forward Cox regression analysis identified that higher baPWV (hazard ratio, 1.001; P=0.001), lower baseline eGFR, and higher serum phosphate level were independently associated with progression to commencement of dialysis or death. Our results show an independent association between baPWV and renal function decline and progression to commencement of dialysis or death in patients with CKD. Screening CKD patients by means of baPWV may help identify a high-risk group of rapid renal function decline and progression to commencing dialysis or death.

High phosphate diet reduces atherosclerosis formation in apolipoprotein E-deficient mice

Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E-deficient mice.

Troponin I levels in asymptomatic patients on haemodialysis using a high-sensitivity assay

Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (≥0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level.

Niacin as potential treatment for dyslipidemia and hyperphosphatemia associated with chronic renal failure: the need for clinical trials

Niacin has profound and unique effects on lipid metabolism. In addition to increasing high-density lipoprotein cholesterol, it is also known to decrease total cholesterol, low-density lipoprotein cholesterol, and triglyceride. Interestingly, the plasma concentration of lipoprotein(a) [Lp(a)], which has been suggested to play a role as an independent risk factor for coronary heart disease, is also decreased by niacin. Therefore, it is not surprising that in the literature it was given unique description as broad-spectrum lipid drug. Its impact is referred to as desirable normalization of a range of cardiovascular risk factors. However, its clinical use is limited due to harmless but unpleasant unique side effect of cutaneous flushing. Interestingly, recent experimental and clinical studies suggest the potential benefit of niacin as a treatment of dyslipidemia and high plasma phosphate associated with chronic kidney disease (CKD). Both dyslipidemia and high serum phosphate levels are shown to be associated with higher cardiovascular mortality. Furthermore, niacin administration improves renal tissue lipid metabolism, renal function and structure, hypertension, proteinuria, and histological tubulointerstitial injury. Further studies are required before the use of niacin for the treatment of both dyslipidemia and hyperphosphatemia with CKD advocated.

Intima-Media Thickness of the Carotid Artery and Its Correlation Factors in Maintenance Hemodialysis Patients: A Cross-Sectional Study

Background: To investigate the relationship between the intima-media thickness of the carotid artery (CA-IMT) and its major risk factors in maintenance hemodialysis (MHD) patients. Methods: Seventy-five MHD patients and 30 healthy volunteers were enrolled. The MHD patients were divided into 3 subgroups according to their CA-IMT value. Results: CA-IMT values in the MHD group were significantly higher than those in the control group. The differences in age, systolic blood pressure (SBP), and levels of serum albumin, prealbumin, cholesterol and serum phosphate between the increased IMT group and the normal IMT group were significant. SBP and serum phosphate levels were also greater in the abnormal IMT group than those in the normal IMT group. Significant relationships were found between CA-IMT and age, SBP, and serum levels of phosphate, albumin and prealbumin. In multiple regression analysis, a high serum phosphate level, low serum prealbumin level and high SBP were significant independent risk factors of increased CA-IMT. Conclusions: CA-IMT was increased dramatically in MHD patients. A high serum phosphate level, low serum prealbumin level and high SBP may be associated with advanced arteriosclerosis.

Phosphorus and Survival

For more than forty years now, high serum phosphate levels, a highly prevalent condition in patients with chronic kidney disease (CKD), have been associated with the pathogenesis of secondary hyperparathyroidism, a common mineral and bone disorder (MBD).1 Recent epidemiologic and experimental studies have further amplified the role this condition plays in the larger story of CKD-MBD. Experimental studies have demonstrated that high phosphorus plays a key role in the development of vascular calcification2 and impairment of bone mass and strength, induces changes in the expression pattern of muscle and bone-related genes,3,4 and may also act as a pro-aging factor.5 In addition, clinical studies have demonstrated an association among hyperphosphatemia, vascular stiffness, and left ventricular hypertrophy.6 Taking all of the aforementioned findings together, it is reasonable to hypothesize all these untoward actions of phosphorus may ultimately affect mortality, as it has been suggested by several studies carried out in different dialysis cohorts.7,8 The increase in the importance of phosphorus in the spectrum of CKD-MBD also coincides with the description of the multiple actions of a new modulator, fibroblast growth factor 23 (FGF-23). This phosphatonin carries out some effects independent of phosphorus, such as its inhibitory effect on parathyroid hormone synthesis,9 but, so far, most of the biologic actions of FGF-23, including its recently described association with mortality,10 seem to be highly interdependent and related …

Insuffisance rénale chronique : de la maladie osseuse à la maladie osseuse et vasculaire

The accelarated atherosclerosis occurring in patients with chronic renal failure (CRF) is a well-known complication since the beginning of dialysis. The relationship between vascular lesions and phosphocalcic abnormalities is a more recent concept. The relationship between increase in phosphate × calcium product and cardiac valvular calcifications was demonstrated in 1980. The relationship between high serum phosphate levels and mortality was shown in 1998. The strong prevalence of coronary calcifications in CRF patients was shown in 1996. In 2000, the association between these calcifications and the oral dose of calcium was strongly suggested. Thereafter, the mechanism of these calcifications appeared much more complex, involving hypercholesterolemia, inflammation, and other factors. The relationships between hyperparathyroidism and mortality were shown during the years 2000. There is also an association between hypoparathyroidism and mortality in dialysis patients but not in CRF patients before the dialysis stage. Another new concept is the discovery of a relationship between vitamin D deficiency, very frequent is CRF patients, and mortality. Treatment with active 1,25(OH)D is associated with a better survival. There is also an new interest in treatment with the 25(OH)D form since the enzyme 1-alpha-hydroxylase, which is responsible for its transformation in active form, is present in multiple organs.

In vivo genetic evidence for klotho‐dependent, fibroblast growth factor 23 (Fgf23) ‐mediated regulation of systemic phosphate homeostasis

A major breakthrough in systemic phosphate homeostasis regulation was achieved by the demonstration of strikingly similar physical, morphological, and biochemical phenotypes of fibroblast growth factor 23 (Fgf23) and klotho ablated mice, which led to identification of klotho as an Fgf23 signaling cofactor. Here, we generated Fgf23 and klotho double-knockout (Fgf23(-/-)/klotho(-/-)) mice to test the hypothesis whether Fgf23 has a klotho-independent function. Fgf23(-/-)/klotho(-/-) mice are viable and have high serum phosphate levels, similar to Fgf23(-/-) and klotho(-/-) single-knockout mice. In addition, the Fgf23(-/-)/klotho(-/-) mice have increased renal expression of the sodium/phosphate cotransporter NaP(i)2a and of 1- alpha-hydroxylase concomitant with increased serum levels of 1,25-dihydroxyvitamin-D, as also observed in the Fgf23(-/-) and klotho(-/-) mice. Moreover, Fgf23(-/-)/klotho(-/-) mice show soft tissue and vascular calcification, severe muscle wasting, hypogonadism, pulmonary emphysema, distention of intestinal wall, and skin atrophy, all of which are also seen in Fgf23(-/-) and klotho(-/-) mice. Notably, injection of bioactive FGF23 protein into Fgf23(-/-)/klotho(-/-) and klotho(-/-) mice does not lower serum phosphate, whereas in wild-type and Fgf23(-/-) mice, it reduces serum phosphate. Together, these results provide compelling evidence that Fgf23 does not have a klotho-independent role in the regulation of systemic phosphate and vitamin D homeostasis.

Increased inorganic phosphate induces human endothelial cell apoptosis in vitro

Chronic kidney disease with hyperphosphatemia is associated with accelerated atherosclerosis and endothelial dysfunction. However, the contribution of high serum phosphate levels to endothelial injury is incompletely understood. The aim of this work was to evaluate the responses of endothelial cells to elevated levels of extracellular phosphate in vitro. High phosphate in concentrations similar to those observed in uremia-associated hyperphosphatemia (>2.5 mM) induced apoptosis in two endothelial cell lines (EAhy926 cells and GM-7373 cells). This effect was enhanced when cells were incubated for 24 h in the presence of 2.8 mM calcium instead of 1.8 mM. By treating cells with 0.5 or 1.0 mM phosphonoformic acid, an inhibitor of the phosphate transporter, death was completely prevented. The process of phosphate-induced apoptosis was further characterized by increased oxidative stress, as detected by increased ROS generation and disruption of the mitochondrial membrane potential at approximately 2 h after treatment, followed by caspase activation. These findings show that hyperphosphatemia causes endothelial cell apoptosis, a process that impairs endothelial integrity. Endothelial cell injury induced by high phosphate concentrations may be an initial event leading to vascular complications in patients with chronic kidney disease.

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).

Comparison of colon-cleansing methods in preparation for colonoscopy - Comparative efficacy of solutions of mannitol, sodium picosulfate and monobasic and dibasic sodium phosphates

Colonoscopy plays an essential role in the therapeutic and diagnostic approach in various colonic pathologies, the aim of the present study was to compare three solutions and their efficacy for the bowel preparation in adult patients submitted to elective colonoscopy. Sixty patients were randomly divided into three groups of 20 each. Each group was submitted to a bowel preparation with one of the following solutions: 10% manitol, sodium picosulphate or sodium phosphate. The parameters evaluated were: taste, tolerance, associated side effects and quality of cleansing. Postural blood pressure and pulse rate as well as serum sodium, potassium, calcium and phosphate were compared. Sodium phosphate and 10% manitol solutions provided superior results in terms of colon cleansing compared to sodium picosulphate solution. All serum electrolytes evaluated were significantly altered in the three groups, without important clinical signs. High levels of serum phosphate were the most striking alteration in patients prepared with sodium phosphate solution, again with no clinical signs. Variations related to blood pressure and pulse rate suggested contraction of intravascular volume, with no clinical effects. Sodium phosphate and 10% manitol solutions are equivalent in providing good quality colon cleansing, with no significant side effects that could compromise the procedure.

Causes and Differential Diagnosis of Hypocalcemia -Recommendation Proposed by Expert Panel Supported by Ministry of Health, Labour and Welfare, Japan-

Serum calcium (Ca) level is maintained within a narrow range mainly by actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitmain D [1,25(OH)(2)D]. While it is not rare to encounter hypocalcemia in clinical practice, there is currently no practical guideline for the differential diagnosis of hypocalcemia. We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many genetic or other causes have been identified recently. Hypocalcemia can be divided into two categories, hypocalcemia with low serum phosphate level, and one with normal to elevated serum phosphate level. Deficient actions of 1,25(OH)(2)D, loss of Ca into urine, and deposition of Ca in bone or soft tissues are main causes of hypocalcemia with low to low normal serum phosphate level. Hypocalcemia with high normal to high serum phosphate level includes chronic renal failure and hypoparathyroidism. Hypoparathyroidism is subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism. Recent investigations identified several causes of PTH-deficient hypoparathyroidism, including genetic abnormalities and parathyroid autoantibodies, which should be differentiated from idiopathic hypoparathyroidism. Physical and laboratory findings, the time of the onset of diseases and accompanying illness can be clues for identifying causes of PTH-deficient hypoparathyroidism.

Efecto hipolipemiante y antiinflamatorio del sevelamer en pacientes en diálisis peritoneal

Background Sevelamer hydrochloride is a non-absorbable, aluminium-and calcium-free ion-exchange resin with proven efficacy and safety in hemodialysis patients. However, until now, little information has been available on the efficacy and safety of this molecule in peritoneal dialysis patients. Patients and method We analyzed the effects of sevelamer hydrochloride through a cross-sectional study of 228 patients under peritoneal dialysis in 10 dialysis units in Catalonia and the Balearic Islands (Spain). Results At the time of the study, 56 % patients were receiving sevelamer. Patients receiving sevelamer were younger (p < 0.01), had been under dialysis for longer (p < 0.01) and had a lower Charlson comorbidity index (p < 0.01) than patients not receiving this drug. Serum calcium levels and intact parathyroid hormone (i-PTH) levels showed no differences between the 2 groups, while sevelamer-treated patients and higher levels of serum phosphate and calcium-phosphate product. Phosphate levels < 5.5 mg/dl were observed less frequently in patients receiving sevelamer (61 % vs. 79 %; p < 0.01). Total serum cholesterol (167 ± 41 vs. 189 ± 42 mg/dl; p < 0.0001) and low-density lipoprotein cholesterol (90 ± 34 vs. 109 ± 34 mg/dl; p < 0.0003) levels were lower in sevelamer-treated patients. Moreover, sevelamer-treated patients displayed higher serum albumin (38 ± 5 vs. 36 ± 4 g/l; p < 0.01) and lower C reactive protein (4.9 ± 12.8 vs. 8.8 ± 15.7 mg/l; p < 0.01) levels, revealing better nutritional and inflammatory status. Blood bicarbonate levels were lower in patients receiving sevelamer (24 ± 3.2 vs. 26.7 ± 3.2 mmol/l; p < 0.01). Conclusions Sevelamer hydrochloride treatment may have an anti-inflammatory effect in addition to improving lipid profile and achieving good phosphate levels, similar to those achieved in patients under hemodialysis. We recommend close monitoring of bicarbonate levels in this group of patients.

Regulation of parathyroid hormone mRNA stability by calcium, phosphate and uremia

This review focuses on the regulation of parathyroid hormone gene expression by dietary-induced hypocalcemia, hypophosphatemia and uremia. Understanding the mechanism by which calcium and phosphate regulate parathyroid hormone gene expression is important for both normal physiology and in pathological states, especially chronic kidney disease. Calcium and phosphate regulate parathyroid hormone secretion, gene expression and, if prolonged, parathyroid cell proliferation. Chronic kidney disease is characterized by a high serum phosphate level that often leads to secondary hyperparathyroidism. In the rat, regulation of parathyroid hormone gene expression by calcium, phosphate and uremia is posttranscriptional, affecting mRNA stability. Differences in binding of protective trans-acting proteins to a conserved protein-binding cis-acting instability element in the parathyroid hormone mRNA 3'-untranslated region alter parathyroid hormone mRNA stability. Two trans-acting proteins - adenosine-uridine rich binding factor 1 and Up-stream of N-ras- stabilize parathyroid hormone mRNA in vivo and in vitro. Parathyroid hormone mRNA also interacts with mRNA decay-promoting proteins and ribonucleases that lead to parathyroid hormone mRNA degradation. Calcium, phosphate and uremia determine parathyroid hormone mRNA stability through the binding of the protective factors adenosine-uridine rich binding factor 1 and Up-stream of N-ras and the recruitment of a degradation complex that cleaves parathyroid hormone mRNA.