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New Blood Test Might Identify Calcification- Prone Patients

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New Blood Test Might Identify Calcification- Prone Patients K IdNey WeeK edITIoN October/November 2012 | Vol. 4, Numbers 10 & 11 New Blood Test Might Identify Calcification- Prone Patients By Tracy Hampton lthough vascular and soft tis- recent issue of the Journal of the Ameri- sue calcification can be deadly, can Medical Association, could change physicians currently have no practice and provide an effective way to Areliable tools for determining an indi- measure an individual’s overall propen- vidual’s calcification risk. This is par- sity for calcification in serum (Pasch A, ticularly pertinent to nephrologists et al. J Am Soc Nephrol doi: 10.1681/ and others who care for patients with ASN.2012030240 [published online compromised kidney function because ahead of print September 6, 2012]). pathologic vascular calcification has “This test may help to identify cal- been called “the killer of patients with cification-prone patients to guide and chronic kidney disease” (Mizobuchi M, monitor their treatment. We regard this et al. J Am Soc Nephrol 2009; 20:1453– as an important step ahead in the field 1464). of calcification research and of poten- “We currently have quite a good tial importance for the treatment of pa- idea about pathomechanisms triggering tients with kidney disease worldwide,” progressive calcification, and we think said first author Andreas Pasch, MD, of we know about a number of clinical fac- University Hospital and University of tors predicting calcification progression Bern, Inselspital, in Switzerland. including hyperphosphatemia, high calcium burden, and inflammation,” c alculating calcification said Markus Ketteler, MD, head of the Calcifications in the body mainly con- division of nephrology at the Univer- sist of two components, calcium and sity Hospital Würzburg, in Germany. phosphate, which combine to form cal- “However, none of these factors shows cium phosphate. Because calcium and a clear-cut linear relationship with the phosphate concentrations in the blood magnitude or progression of cardiovas- are naturally near supersaturation, the cular calcification or related events.” balance of inhibitors and promoters of Now a newly developed nanoparti- cle-based test, which is described in a Continued on page 3 Inside k Idney Week ScIentIfIc SeSSIonS Stone Formation in Dent’s Disease n4 ew at kidney Week 20 tHURSdAy Tolerance and Kidney Transplantation Jack W. Coburn Endowed Lectureship: Rajesh V. Thakker 6 ASn in Review Stare-of-the-Art Lecture: David H. Sachs Allocation of Health Care: Dialysis and Beyond Christopher R. Blagg Endowed Lectureship: Bruce C. Vladeck 9 ASn President and President- Sepsis AKI: Kidney as Amplifier and Target elect Q/A Robert W. Schrier Endowed Lectureship: Robert A. Star 14 Policy Update Mutations in the K+ Channel KCNJ5 Produce Primary 26R SAtU dAy Aldosteronism Entering the Era of Genomic Medicine: Research Opportunities 18 Are Health disparities Helped Barry M. Brenner Endowed Lectureship: Richard P. Lifton and Challenges by Quality Improvement? State-of-the Art Lecture: Eric D. Green 32 Journal View 22 fRIdAy 37 do Bundled Payments Affect Health Care Reform in America—Past, Present, and Future 28d SUn Ay Quality of care? State-of-the-Art Lecture: William L. Roper Where Kidney Disease Was and Where It Is Headed State-of-the-Art Lecture: Robert W. Schrier 39 Industry Spotlight Renal Glucose Transport from Man to Molecule Homer W. Smith Address: Ernest M. Wright Podocyte Biology: The Key to Understanding Glomerular Disease Young Investigator Award: Tobias B. Huber This is how we see the numbers. Unlike other labs, our kind of number crunching doesn’t compromise patient care. And that’s because we firmly believe that the best way to help you navigate the new CMS Bundle is to maintain the level of expertise, clinical support, and service you’ve come to rely on—including comprehensive laboratory testing with no hidden fees. And in our eyes, offering everything to you for one fair price isn’t just the right thing to do. It’s the right thing for your patients. ® www.spectra-labs.com © 2012 Fresenius Medical Care Holdings, Inc. All rights reserved. ACCREDITED Spectra ® and the Spectra logo are trademarks of Fresenius Medical Care Holdings, Inc. CalculatorAd-ASN.indd 1 12/9/11 2:31 PM October/November 2012 | ASN Kidney News | 3 Calcification- tored with a commercial nephelometer, properties to inhibit calcification. Blood plications are promising, “future experi- a photometer measuring scattered light. from healthy volunteers did not. mental and clinical studies are essential Prone Patients The test by Pasch and his team measures “The test by Pasch et al. could show in order to establish this calcification clear differences in calcification inhibi- test for clinical use. These data need Continued from page 1 the kinetics of CPP transformation by detecting the changes in light scatter in tory capacity of calcification-prone fe- to be confirmed in patient cohorts in these minerals critically influences the a sample of serum. In its current format, tuin-A knockout mice and dialysis pa- prospective studies, especially in con- development of calcification. Under the assay can measure approximately tients versus wild-type mice and healthy junction with outcome parameters,” physiologic conditions, calcium and 200 serum samples per day. volunteers, respectively,” said Georg Schlieper said. phosphate mineralize only in bones Schlieper, MD, an assistant professor Ketteler added that “in addition to and teeth, but pathologic states can Getting to the clinic at the RWTH Aachen University Hos- systemic or circulating calcification- lead to soft tissue and vascular calcifi- pital, in Germany. “This discrimination modifying factors, there are some potent To prove the test’s utility, the research- cations. appears as a very promising approach in locally expressed and active calcification ers showed that in the presence of arti- Intensive treatment, especially self- identifying patients at high risk for cal- inhibitory systems at work—including ficially elevated calcium and phosphate medication with calcium-containing cification and has the later potential to matrix Gla protein, or MGP, and py- concentrations, their new nanoparticle- antacids and over-the-counter oste- guide through decalcification therapy.” rophosphates—which may not be de- based assay detected the spontaneous oporosis drugs, has led to a resurgence In other words, the test may also be- tected here.” transformation of primary CPPs to sec- of the “milk alkali syndrome” associ- come an important tool for identifying The test in its current form requires ondary CPPs. Also, the test found that ated with soft tissue calcifications and and testing calcification inhibitors and strict temperature control and liquid both the sera of mice deficient in fetuin- kidney damage. Also, patients with may provide the basis for treatment handling. Further automation and sim- chronic kidney disease often have ab- A, a serum protein that inhibits calcifi- monitoring in patients who receive such plification could help make the test normally high blood calcium levels cation, and the sera of patients receiv- inhibitors. more useful for basic and clinical re- because of their compromised kidney ing hemodialysis had reduced intrinsic Whereas the findings and their im- search, the investigators said. function and metabolic insults of dia- betes, dyslipidemia, oxidative stress, uremia, and hyperphosphatemia. “Despite much progress in our molecular understanding of calcium homeostasis—particularly the role of the calcium-sensing receptor, renal phosphate handling, and epithelial cal- cium channels that are present in vari- ous tissues—the clinical determinants of pathologic calcifications are still incompletely understood,” said Pasch. “Individual calcification risk cannot be determined, and patients particularly [likely] to develop calcifications cannot be identified.” Given the major clinical problem of accelerated calcification in many patients with chronic kidney disease, Pasch and his team set out to develop the first potentially widely available blood test that functionally integrates ™ all the procalcification and anticalci- fication forces inherent in blood with one single measurement to obtain an estimate of the calcification propensity of individual serum samples. The researchers found that when se- Real-Time Dialysis Monitoring rum is artificially challenged with high Providing the only real-time dialysis adequacy monitoring software, Adimea is a amounts of calcium and phosphate, technologically advanced system that provides continuous and accurate Kt/V and URR so-called primary calciprotein particles monitoring throughout the patient’s dialysis treatment. Adimea simply requires the (CPPs) are formed. CPPs are protein- entry of the patient’s weight. mineral aggregates that consist mainly of calcium, phosphate, and the two Once activated, the Adimea user interface provides: calcification-inhibiting serum proteins Cumulative display of URR and Kt/V fetuin-A and albumin. Calcium and Selection and monitoring of target Kt/V value phosphate form an amorphous or col- Fast access to treatment parameters to influence outcome loidal state in primary CPPs, but with time, primary CPPs transform into secondary CPPs, which consist of a Adimea is: spectrum of proteins as well as crystal- Easy to use line (as opposed to colloidal) calcium Cost effective — no additional disposable cost or per treatment cost phosphate. “The speed of transforma- No blood sampling required tion is a measure of calcification in- hibition,”
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