Decrease In Serum Phosphate Levels Research Articles

Elderly-onset calcinosis of hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome: the role of comorbid scleroderma.

A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered. HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases. HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis. Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.

Improved β2-Microglobulin and Phosphorous Removal with Expanded Hemodialysis and Online Hemodiafiltration versus High-Flux Hemodialysis: A Cross-Over Randomized Clinical Trial

Introduction: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of β2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol. Methods: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET. Results: Twenty-two patients were included, β2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (−0.79 mg/dL vs. −1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET. Conclusion: HDx provides enhanced removal of β2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies.

MO809: Sucroferric Oxyhydroxide for the Management of Hyperphosphataemia in Peritoneal Dialysis Patients

Abstract BACKGROUND AND AIMS Bone and mineral metabolism disorders are very common in chronic kidney disease (CKD) patients. The increase in phosphorus levels leads to bone disease, risk of calcification and higher mortality, so any strategy aimed at reducing it should be welcomed. The latest drug added to the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SO). Our objective was to analyse the efficacy and safety of SO in patients with CKD on peritoneal dialysis (PD), followed for 6 months. METHOD Observational, multicentre, prospective, clinical practice study. Patients who had been on PD for &amp;gt;6 months and who had been prescribed SO as a treatment for hyperphosphataemia were included; they should also meet any of the following conditions: serum phosphate &amp;gt;4.5 mg/dL, serum phosphate ≤4.5 mg/dL but receiving a high number of tablets or using another phosphate binder with adverse effects or intolerance. Clinical and epidemiological variables were analysed; also parameters related to bone and mineral metabolism disorders and anaemia. Variations in stool consistency and the need for laxatives were also taken into account. RESULTS A total of 92 patients (62 ± 14 years, 66% male, 23% diabetic), from 11 centres, were included in the study. In 66 patients (72%), SO was the first phosphate binder; in the other 26, a previous binder was replaced by SO due to lack of tolerance or efficacy. The initial dose of SO was 942 ± 516 mg/day. Globally, serum phosphate levels decrease at 3 (10.7%, P &amp;lt; .001) and at 6 months of treatment (18.3%, P &amp;lt; .001). After 6 months of treatment, 63% of the patients achieved a phosphataemia of &amp;lt;5 mg/dL and 41% &amp;lt;4.5 mg/dL. The decrease in serum phosphate levels correlated with baseline phosphate level (r = 0.367; P = .039), age (r = .338; P = .033) and time on dialysis (r = 0.578; P = 0.001). There were no differences in the efficacy of the drug when comparing the different populations analysed. Serum levels of calcium, iPTH, ferritin, transferrin saturation index and haemoglobin did not change throughout the study. Stool consistency was reduced, and the need for laxatives decreased by 18%. The mean dose of SO increased over time to 1167 ± 381 mg/day. The drug was well tolerated. CONCLUSION SO is an effective option for the treatment of hyperphosphataemia in PD patients. Age, basal phosphate levels and time in the technique are factors associated with a greater decrease in serum phosphate levels. Stool consistency became softer (which may improve dialysis efficiency) with less need for laxatives.

Proton pump inhibitors may hinder hypophosphatemic effect of lanthanum carbonate, but not of ferric citrate hydrate or sucroferric oxyhydroxide, in hemodialysis patients

Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 9), while a dosage of 700 ± 230 mg/day only decreased it by −3% in the presence of a PPI (n = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 7, FCH: 571 ± 189 mg/day) and by −17% in the presence of a PPI (n = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was −7% in the absence of a PPI (n = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by −13% in the presence of a PPI (n = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

Dental manifestations of the hypophosphatemic rickets: A case report

Rickets is a disorder of bone mineralization in children?s skeleton. It is most often associated with vitamin D deficiency, however, it can also occur due to a decrease in serum phosphate levels, which leads to inadequate tissue mineralization, with consequent skeletal deformity and growth disorders. Patients with hypophosphatemic rickets show teeth changes at the morphological and histological level, as well as on radiological images. The aim of this study was to perform clinical and radiological evaluation of dental manifestations of hypophosphatemic rickets in a four-year-old boy, as well as to point out the necessity of including a dentist in the treatment of this disease in order to prevent oral complications.

Effects of Short Term Alendronate Administration on Bone Mineral Density in Patients with Chronic Kidney Disease.

Abstract Background: Osteoporosis is highly prevalent in CKD patients and is characterized by low bone mass leading to decreased bone strength. It is associated with an increased risk of fracture, thus increasing morbidity and mortality. Bisphosphonate administration decreases fracture risk in postmenopausal females with osteoporosis. There are limited studies showing effects of short term alendronate administration on BMD in predialysis osteoporotic patients with CKD. Methods: This study was conducted on fifty adult patients with chronic kidney disease. Patients were divided into two groups. Group A consisted of seventeen patients with CKD stage 3 (eGFR 45-30 ml/min/1.73m2) and Group B comprised thirty three patients with CKD stage 4 (eGFR 30-15 ml/min/1.73m2). The study included male patients between age 18-75 years and premenopausal non pregnant females older than 18 years of age. All the patients were osteoporotic having T score &lt; −2.5 on DEXA scan. The patients were administered 70 mg alendronate tablet once a week for 6 weeks. Renal parameters, parathyroid hormone, calcium, phosphorous and alkaline phosphatase levels were assayed at baseline for 6 months. Serum (iPTH) level (pg/ml) was measured by chemiluminescent immune assay (CLIA) method and serum 25 Hydroxy Vitamin D level (ng/ml) was measured by enzyme linked immunosorbent assay (ELISA) method. Bone Mineral Density (BMD) was measured at baseline for 6 months, by dual energy x-ray absorptiometry at lumbar spine and neck of femur and lowest values were included. The results were obtained for T score, Z score and bone mineral density (g/cm2). Results: The BMD, T score and Z score increased in both groups after 6 months with a statistically significant difference in the treatment group. In Group A, T score, Z score and BMD (g/cm2) increased from −2.60±0.086, −2.13±0.28, and 0.80±0.008 at baseline to −2.57±0.097, −2.11±0.26 and 0.81±0.008 after six months. In Group B, the T score, Z score and BMD (g/cm2) increased from −3.17±0.24, −2.82±0.33 and 0.738±0.03 to −3.16±0.25, −2.66±0.95 and 0.743±0.03 after six months with a statistically significant difference. eGFR decreased in both groups but the difference was statistically non-significant (P&gt;0.05). The serum iPTH levels increased after 6 months in both groups with a statistically insignificant difference. There was an increase in serum calcium and decrease in serum phosphate levels after six months, however the difference was statistically insignificant (p&gt;0.05). The SAP values decreased in both groups after six months with a statistically insignificant difference. The main side-effect in the alendronate group was the occurrence of gastroesophageal reflux symptoms in two subjects. Conclusion: Low-dose alendronate, administered for a limited duration, appears to be well tolerated in CKD patients. The BMD increased in both groups suggesting a bone-preserving effect of alendronate.

Renal Phosphate Reabsorption is Correlated with the Increase in Lumbar Bone Mineral Density in Patients Receiving Once-Weekly Teriparatide.

In order to assess the changes in serum calcium and phosphate and the changes in renal tubular phosphate reabsorption (TmP/GFR) and to evaluate the association between these indices and the increase in bone mineral density (BMD) with once-weekly intermittent administration of teriparatide (TPTD), the results from the teriparatide once-weekly efficacy research (TOWER) trial were re-analyzed. The TOWER trial studied postmenopausal women and older men with osteoporosis. Patients were randomly assigned to receive TPTD 56.5 μg or placebo for 72 weeks. Of these patients, the present study investigated those whose calcium and phosphate levels and lumbar BMD (L-BMD) were measured (TPTD group, n = 153 and Placebo group, n = 137). The TPTD group had significantly lower serum phosphate, calcium-phosphate product, and TmP/GFR at weeks 4, 24, 48, and 72 and urinary fractional calcium excretion (FECa) at weeks 12, 48, and 72 (p < 0.05). In the TPTD group, the serum phosphate and TmP/GFR during early treatment (4, and 12 weeks) showed a significant positive correlation with the percent change in L-BMD at weeks 48 and 72. Based on multivariate analysis corrected for age, BMI, and L-BMD at the start of treatment, serum phosphate and TmP/GFR at week 4 showed a significant correlation with the percent change in L-BMD. This study suggests that the L-BMD response to once-weekly long-term TPTD treatment is associated with circulating phosphate or with the status of its renal reabsorption. Preventing decrease in serum phosphate levels may be important in acquiring greater L-BMD with once-weekly TPTD.

Patients with elevated serum parathyroid hormone levels after parathyroidectomy: showing signs of decreased peripheral parathyroid hormone sensitivity.

We have previously shown that patients with elevated levels of parathyroid hormone (PTH) after surgery for parathyroid adenoma have normal parathyroid and renal function but demonstrate signs of remineralization of cortical bone, decreased calcium absorption, and low levels of vitamin D. We hypothesized that decreased peripheral PTH sensitivity could also be of importance for this condition. Thirteen patients operated on for a solitary parathyroid adenoma, with a mean +/- SD preoperative serum level of calcium of 2.72 +/- 0.12 mmol/L, were investigated 6 weeks after surgery with a standardized PTH (1-34) infusion test for 6 hours. The eight patients with elevated PTH levels had less increase in serum levels of ionized calcium (0.02 +/- 0.03 mmol/L) than did the five patients with normal PTH levels (0.06 +/- 0.02 mmol/L) (p < 0.05). Patients with elevated PTH also showed less decrease in serum phosphate levels (p < 0.05) and a trend to a larger decrease in the excretion of urinary calcium (p = 0.08). The increase in 1,25-dihydroxyvitamin D(3) did not differ between the two groups of patients. Thus patients operated on for parathyroid adenoma with postoperatively elevated serum PTH levels showed decreased peripheral sensitivity to PTH.

Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women

Estrogen-replacement therapy is important for the prevention of postmenopausal osteoporosis. However, oral synthetic and conjugated estrogens increase biliary cholesterol saturation index and risk of gallstone disease. To examine whether transdermal estrogen administration could avoid these adverse effects, 17 postmenopausal women were treated with transdermal estradiol (Estraderm TTS; Ciba-Geigy, Arnhem, The Netherlands), 100 μg/day for 4 weeks, and after 1 month without therapy, with oral estradiol (Progynova; Schering, Weesp, The Netherlands), 2 mg/day for 4 weeks. The increase in the serum estradiol level was much higher during transdermal than oral estradiol administration. On the contrary, the increase in the serum estrone level was much more pronounced during oral treatment. Both modes of treatment led to a similar reduction of urinary calcium excretion. A highly significant decrease in serum phosphate levels was found during transdermal therapy. Biliary cholesterol saturation index did not change during transdermal therapy (mean ± SEM, 1.25 ± 0.06 before and 1.22 ± 0.07 at the end of transdermal therapy; P = NS). A slight increase in cholesterol saturation index that did not reach statistical significance was found during oral therapy (1.28 ± 0.09 before and 1.36 ± 0.09 during oral treatment). However, the subgroup of women with strong increases in serum estrone levels during oral estradiol therapy (>0.5 pmol/mL; n = 8) generally had increased biliary cholesterol saturation index, a decrease in relative percentage chenodeoxycholic acid in bile, and increased serum sex hormone-binding globulin levels during oral treatment. Cholesterol monohydrate crystals were never found in duodenal biles during either treatment. This study indicates that transdermal estradiol does not induce lithogenic bile. On the contrary, oral estradiol leads to lithogenic bile in a subgroup of women with strong increases in serum estrone levels during oral treatment.

Decreased Serum Phosphate Levels after High-Dose Estrogens in Metastatic Prostate Cancer. Possible Implications

Hypophosphatemia and osteomalacia have been described in patients with metastatic prostate cancer. The mechanism of hypophosphatemia in prostate cancer is not known. A decrease in serum phosphate levels was observed in 16 of 18 patients with metastatic prostate cancer treated with high-dose diethylstilbestrol diphosphate. To determine if the fall in serum phosphate was indeed due to diethylstilbestrol diphosphate, the data from several similar groups of patients treated with chemotherapy and combined chemohormonal therapy that included diethylstilbestrol diphosphate were re-examined. Fifty-eight patients were treated with doxorubicin, doxorubicin plus cis-platinum, doxorubicin plus diethylstilbestrol diphosphate, or diethylstilbestrol diphosphate alone. A significant decrease in serum phosphate levels was seen only in patients treated with diethylstilbestrol diphosphate. Hypophosphatemia and possibly osteomalacia in metastatic prostate cancer may be related to estrogen therapy.

Decreased serum phosphate levels after high-dose estrogens in metastatic prostate cancer: Possible implications

Hypophosphatemia and osteomalacia have been described in patients with metastatic prostate cancer. The mechanism of hypophosphatemia in prostate cancer is not known. A decrease in serum phosphate levels was observed in 16 of 18 patients with metastatic prostate cancer treated with high-dose diethylstilbestrol diphosphate. To determine if the fall in serum phosphate was indeed due to diethylstilbestrol diphosphate, the data from several similar groups of patients treated with chemotherapy and combined chemohormonal therapy that included diethylstilbestrol diphosphate were re-examined. Fifty-eight patients were treated with doxorubicin, doxorubicin plus cis-platinum, doxorubicin plus diethylstilbestrol diphosphate, or diethylstilbestrol diphosphate alone. A significant decrease in serum phosphate levels was seen only in patients treated with diethylstilbestrol diphosphate. Hypophosphatemia and possibly osteomalacia in metastatic prostate cancer may be related to estrogen therapy.

Oral Versus Intravenous Administration of Butylbiguanide: Effect on Oral Glucose Tolerance in Normal Humans

1. The effect of oral and intravenous administration of butylbiguanide on the oral glucose tolerance test was investigated in 12 normal human volunteers. Orally administered butylbiguanide lowered the oral glucose tolerance curve and the corresponding serum insulin values, whereas intravenously injected butylbiguanide had no effect. 2. The lactate/pyruvate ratio determined 180 min. after glucose ingestion increased after oral butylbiguanide administration. No effect was observed after intravenous administration. 3. The decrease in serum phosphate levels observed after oral glucose loading was not influenced by butylbiguanide administered by either route. In addition, no effect of this drug was observed on fasting levels of glucose, insulin, phosphate, bicarbonate, lactate and pyruvate. 4. These results are compatible with recent observations that biguanides inhibit active transport mechanisms in the intestine. In addition, the effect of biguanides on blood levels of glucose metabolites is discussed with respect to their known action on oxidative phosphorylation.