Santee, CA, United States
Santee, CA, United States

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Caron P.,Center Hospitalier University Larrey | Simonds W.F.,U.S. National Institutes of Health | Maiza J.-C.,Center Hospitalier University Larrey | Rubin M.,Columbia University | And 5 more authors.
Clinical Endocrinology | Year: 2011

Objective Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0·8). Patients and design Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W-PTH, T-PTH and circulating PTH molecular forms separated by high-pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. Results The first patient had total calcium of 3·8 and 3·22 mmol/l before the fourth and fifth surgeries, and third/second-generation PTH ratios of 2·95 and 3·6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3·6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over-expression of NT-N PTH to 82·2% (N < 10%) relative to hPTH(1-84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W-PTH/T-PTH ratio was 0·89 when serum calcium was 3·3 mmol/l. NT-N PTH was also over-expressed at 51·9%. An inactivating mutation of the HRPT2 gene was also identified. Conclusions This may suggest that a progressive rise in third/second-generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT-N PTH overproduction and HRPT2 gene inactivation is also suggested. © 2011 Blackwell Publishing Ltd.


PubMed | University of Kentucky, Bone and Mineral Metabolism and., Bone and Mineral Metabolism and and Scantibodies Laboratory Inc.
Type: Journal Article | Journal: Journal of the American Society of Nephrology : JASN | Year: 2015

Coronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bone markers. A total of 213 patients received baseline measurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores>400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD-associated CAC prevalence and progression.


Trivedi H.,Medical College of Wisconsin | Szabo A.,Medical College of Wisconsin | Zhao S.,Medical College of Wisconsin | Cantor T.,Scantibodies Laboratory Inc. | And 2 more authors.
Journal of Nephrology | Year: 2015

Background: Mineral and bone parameters are actively managed in end-stage renal disease (ESRD). However, whether these undergo circadian variation is not known. We investigated the circadian variation of mineral and bone parameters in patients on long-term hemodialysis. Methods: Seventeen ESRD patients on long-term hemodialysis and eight volunteers without kidney disease were enrolled. Subjects had all medications that affect calcium–phosphate–parathyroid hormone balance (phosphate binders, vitamin D analogues, and calcimimetics) discontinued. Thereafter, for a period of 5 days, subjects consumed a diet controlled in calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve 2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total 25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23). Results: In the ESRD patients plasma phosphate demonstrated significant circadian variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P = 0.009) also varied significantly during the circadian period; for ionized calcium peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a significant circadian variation. Only phosphate (P < 0.0001) and PTH (P = 0.00008) demonstrated circadian variation in the control group. Conclusions: Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit a circadian variation in patients with ESRD. Knowledge of these phenomena is pertinent for the interpretation of clinical testing. © 2014, Italian Society of Nephrology.


Malluche H.H.,University of Kentucky | Davenport D.L.,University of Kentucky | Canto T.,Scantibodies Laboratory Inc | Monier-Faugere M.-C.,University of Kentucky
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss. Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMDat baseline and changes over 1 year.Multivariable regression was performed to adjust for age, sex, body mass index, and race. Results Eighty-one patients completed the study (mean age=52.6±12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by eithermethod, 33.3%of the patientswere osteoporotic. Baseline BMDcorrelatedwith sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor.At 1 year, hipQCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). ftermultivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT. Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis © 2014 by the American Society of Nephrology.


Malluche H.H.,University of Kentucky | Blomquist G.,University of Kentucky | Monier-Faugere M.-C.,University of Kentucky | Cantor T.L.,Scantibodies Laboratory Inc. | Davenport D.L.,University of Kentucky
Journal of the American Society of Nephrology | Year: 2015

Coronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bonemarkers. A total of 213 patients received baselinemeasurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores.400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD-associated CAC prevalence and progression. Copyright © 2015 by the American Society of Nephrology.


Herberth J.,University of Kentucky | Branscum A.J.,University of Kentucky | Mawad H.,University of Kentucky | Cantor T.,Scantibodies Laboratory Inc | And 2 more authors.
American Journal of Kidney Diseases | Year: 2010

Background: Determination of parathyroid hormone (PTH) level is the most commonly used surrogate marker for bone turnover in patients with stage 5 chronic kidney disease on dialysis therapy (CKD-5D). The objective of this study is to evaluate the predictive value of various PTH measurements for identifying low or high bone turnover rate. Study Design: Diagnostic test study. Settings & Participants: 141 patients with CKD-5D from 15 US hemodialysis centers. Index Tests: Intact PTH, PTH 1-84, and PTH ratio (ratio of level of PTH 1-84 to level of large carboxy-terminal PTH fragments). Reference Test or Outcome: Bone turnover determined using bone histomorphometry. Other Measurements: Demographic and treatment-related factors, serum calcium and phosphorus. Results: Patients presented histologically with a broad range of bone turnover abnormalities. In white patients with CKD-5D (n = 70), PTH ratio <1.0 added to intact PTH level <420 pg/mL increased the positive predictive value for low bone turnover from 74% to 90%. In black patients (n = 71), adding PTH ratio <1.2 to intact PTH level <340 pg/mL increased the positive predictive value for low bone turnover from 48% to 90%. Adding PTH ratio >1.6 to intact PTH level of 340-790 pg/mL increased the positive predictive value for high bone turnover from 56% to 71%. Limitations: Because the research protocol called for carefully controlled blood specimen handling, blood drawing and routine specimen handling might be less stringent in clinical practice. By limiting study participation to black and white patients with CKD-5D, we cannot comment on the roles of intact PTH, PTH 1-84, and PTH ratio in other racial/ethnic groups. Conclusion: In black patients with CKD-5D, the addition of PTH ratio to intact PTH measurements is helpful for diagnosing low and high bone turnover. In white patients with CKD-5D, it aids in the diagnosis of low bone turnover. © 2010 National Kidney Foundation, Inc.


Trademark
Scantibodies Laboratory Inc. | Date: 2012-07-27

Biochemical preparations for the treatment of infections; therapeutic agents for the treatment of infections; biological therapeutic preparations for the treatment of infections; biochemical preparations, namely, monoclonal and/or polyclonal antibodies for the treatment of infections.


PubMed | Bone and Mineral Metabolism, Scantibodies Laboratory Inc. and University of Kentucky
Type: Comparative Study | Journal: Clinical journal of the American Society of Nephrology : CJASN | Year: 2014

Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.Eighty-one patients completed the study (mean age=52.6 12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.


Trademark
Scantibodies Laboratory Inc. | Date: 2010-01-29

Biochemical preparations for the treatment of infections; therapeutic agents for the treatment of infections; biological therapeutic preparations for the treatment of infections; biochemical preparations, namely, monoclonal and/or polyclonal antibodies for the treatment of infections.


Trademark
Scantibodies Laboratory Inc. | Date: 2010-02-17

Biochemical preparations for the treatment of infections; therapeutic agents for the treatment of infections; biological therapeutic preparations for the treatment of infections; biochemical preparations, namely, monoclonal and/or polyclonal antibodies for the treatment of infections.

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