Current Concepts and Management Strategies in Chronic Kidney Disease-Mineral and Bone Disorder
From the Division of Nephrology, Department of Medicine, Drexel University College of Medicine and Hahnemann University Hospital, Philadelphia, PA, Manipal University, Manipal, India, and Thomas Jefferson University, Philadelphia, PA. Southern medical journal
(Impact Factor: 0.93).
09/2012; 105(9):479-85. DOI: 10.1097/SMJ.0b013e318261f7fe
The term renal osteodystrophy describes the pathological changes in bone structure in chronic kidney disease (CKD); however, this term fails to describe adequately the adverse changes in mineral and hormonal metabolism in CKD that have grave consequences for patient survival. CKD-mineral and bone disorder (CKD-MBD) is a broader, newly defined term that should be used instead of renal osteodystrophy to define the mineral, bone, hormonal, and calcific cardiovascular abnormalities that are seen in CKD. The new paradigm in the management of renal bone disease is to "think beyond the bones" and strive to improve cardiovascular outcomes and survival. This means treating other aspects of the disease process that go beyond merely controlling parathyroid hormone levels. Primary physicians need to take a proactive approach to the management of CKD-MBD because the disorder begins early in the course of CKD, well before a patient is referred to a nephrologist. This review outlines the evidence behind the understanding of CKD-MBD, its implications for overall mortality, and the latest recommendations for management of CKD-MBD in patients with predialysis CKD.
Available from: Scott Peterman
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The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum.
Design and methods:
The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants.
In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples. In addition, positive correlations, (R2 0.67-0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts.
We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications.
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ABSTRACT: Secondary hyperparathyroidism (SHPT) is frequently a complication in patients with chronic kidney disease,especially among those in the fifth stage. Metabolites and vitamin D analogs are the standard medicines in the prevention and treatment of SHPT. In this work we present preliminary results of the peroral application of paricalcitol in elderly people on hemodialysis. Nine patients (two women and seven men between the ages of 60 and 84) were included in the study. They have been on hemodialysis from two to eleven years. All patients are being treated by hemodialysis, three times a week, four hours per session. The concentration of calcium in the dialysate was 1.5 mmol/l. In all patients the concentration of PTH was five times higher than normal, i.e. 381 pg/ml to 961 pg/ml (average 625 pg/ml). The dosage of paricalcitol was 2-4 meg three time per week. All used sevelamer carbonate as a binder. After nine months of treatement,. the average concentration of PTH was 430 pg/ml and 67 of the patients had a PTH in a range of 150 to 600 pg/ml. Hypercalcemia, i.e. a concentration of Ca >2.55 mmol/l was very rare and did not require an interruption of therapy. It was sufficient to reduce the dosage of medicine temporarily. The population of patients on hemodialysis is increasingly elderly. In this population of elderly patients on dialysis hyperparathyroidism, a concentration of PTH <150 pg/ml, is frequently present. Forthose with SHPT peroral treatment with paricalcitol can be successful with minimal side effects.
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