IN THIS ISSUECatch the wave

Thermo Elia™

We are controls

Say Hello to our new website

Estimate your GFR

SAY HELLO TO OUR NEW WEBSITE!

Somagen’s new website launched June 4th 2012 is a just a few months old—we hope you have had an opportunity to browse around and see our new look.

Our Inspired by you home page helps makes your visit more inter-active and much more informa-tive. Our products page is packed with useful product information along with a complete library of past Somagen Quarterly articles. Get to know members of the Somagen team sign up for a sub-scription to Somagen Quarterly or learn about our latest products. We welcome your comments. Please visit us often—there is always something new and exciting at Somagen Diagnostics!

www.somagen.com

CATCH THE WAVE! TOTALLY AUTOMATED RAPID IMMUNOHISTO- CHEMISTRY SYSTEM

Wave technology revolutionizes Immunohistochemistry – results in 75 minutes!Somagen Diagnostics is excited to announce our new partner, Celerus Diag-nostics. Celerus Diagnostics has designed the revolutionary Wave® RPD System that performs totally automated Rapid Immuno-histochemistry (IHC) on formalin-fixed, par-affin-embedded (FFPE) tissue specimens in about an hour.

Fast…Using advanced Aerospace Designed pro-prietary technology, the Celerus Wave® RPD System can produce FFPE results in 75 minutes and frozen tissue sample results in 15 minutes.

Green…Green in its design and construction using RoHS Guidelines (Restriction of Use of Hazardous Substances)the Wave RPD also remains the greenest IHC stainer on the market with respect to daily operation. There is no liquid waste to manage, requiring no external bottles or tubing—the Wave® RPD System uses a wicking cassette absorbing system. This novel approach transforms the little liquid waste generated to a solid state for safe, ergonomic & eco-friendly handling.

Easy to Use…The Wave® RPD System is equipped with a large integrated tactile screen & intuitive software. Ready-to-use cartridge-based reagents and detection chemistries in plug and play format with no offline reagent preparation required.

Quality Staining with Standardized Results…The cartridge based Linear Reagent Magazine (LRM) includes all pre-treatment and detection reagents, hematoxylin and wash buffer. The Wave Primary Antibody Cartridge (PAC) are available in ready-to-use and user fillable format. Both LRM and PAC work together to perform standardized & fully automated Rapid IHC®. Proprietary parallel processing combined with Wave mixing Kinetics insures precise, identical staining and processing for all slides on board.

Limitless Flexibility…Large volume laboratories or high-volume applications can take advantage of the ad-ditional capacity capability of the Wave® RPD System—additional instruments can be added as independent work stations or connected to a central unit.

Lean FriendlyDesigned to process small batches with a much faster TAT(Turnaround time), the Wave RDP adapts well to a lean environ-ment. This allows the option to handle the lab workload in a case by case fashion with less slide sorting from one work station to the next.

Please contact Somagen Diagnostics to learn the many benefits of the Celerus Wave® RPD.

Q2 - WINTER 2012 VOLUME 14, NUMBER 4

2

EliA™ Calprotectin—early diagnostic treatment course in a fast automated cost efficient systemFecal calprotectin is a highly sensitive and specific marker for inflammation of the intestinal tract. A negative result will help rule out an inflammatory process—a positive result may guide the clinician to consider endoscopy.1

Fecal calprotectin is an efficient marker for therapeutic effectiveness and mucosal healing—its levels correlate very well with histological findings in IBD2 3. Recent studies have shown that it is possible to predict relapse of Crohn’s disease and ulcerative colitis.

Calprotectin is a calcium and zinc binding protein found mainly in the cytoplasm of neutro-phils and granulocytes, monocytes and macrophages—pathogen defense cells. Calprotectin demonstrates bacteriostatic and fungistatic properties in vitro. In neutrophil granulocytes it accounts for 60% of cytoplasmic protein.

PERFORMANCE

EliA™ Calprotectin demonstrates outstanding sensitivity and specificity as shown below in table 1. Importantly these high predictive values and likelihood ratios offer excellent values ensuring high clinical utility in routine practice.

High clinical value ELIATM Supplier 1 Supplier 2

Sensitivity 97.7% 96.7% 99.2%

Specificity 89.8% 89.8% 76.3%

Positive Predictive Value 0.96 0.96 0.90

Negative Predictive Value 0.95 0.93 0.98

Positive Likelihood Ratio* 9.58 9.48 4.19

Negative Likelihood Ratio* 0.03 0.04 0.01

Table 1: Performance data of Elia™ Calprotectin and tests from two other suppliers (internal study)

* LIKELIHOOD RATIOS – DIAGNOSTIC EVIDENCE OR NOT

Likelihood ratios use the sensitivity and specificity of a test to determine if the positive or negative result of a diagnostic test changes the probability of the patient actually being af-flicted with the disease.

THERMO ELIA™ CALPROTECTIN... IS IT INFLAMMATION?

EliA™ Calprotectin – fast, fully automated testingRoutine stool extraction samples are pro-cessed automatically by the Phadia® Labo-ratory Systems by reducing the workload for the lab personnel. The Phadia® 250 is designed to meet the specific needs of the laboratory. EliATM Calprotectin can easily be performed together with EliATM serum tests for celiac disease or food allergy, even simultaneously. This provides flexibility, saves costs, and assures a quick delivery of results for improved service quality.

Fecal Calprotectin – a precise marker for intestinal inflammation: non-invasive, specific, and sensitiveInflammation is characterized by an in-creased activity of “pathogen fighting cells” such as neutrophils which release sub-stances such as Calprotectin. In intestinal inflammation the intestinal wall barrier is compromised allowing neutrophil granulo-cytes to migrate into the intestinal lumen. This leads to an elevated level of calprotec-tin in stool.4 The level of fecal calprotectin correlates directly to the number of neutro-phils in the intestinal lumen. Therefore it is specifically elevated in inflammatory bowel diseases (IBD) such as Crohn’s disease and Ulcerative Colitis and to a lesser extent with neoplasia and polyps. This correlation makes stool calprotectin a very sensitive and specific marker as an indicator of intes-tinal inflammation.4

The level of calprotectin in feces is approximately 6 times higher than in serum. This makes stool testing more sensitive in addition to its higher specificity for intestinal diseases.1

RECOMMENDED AS A FIRST LINE TEST

In addition to CRP, ESR and stool culture, stool calprotectin measurement is useful as a screening test for patients reporting GI problems.1 Complaints such as abdominal pain, diarrhea and bloating are common and require various therapeutic approach-es—it is important to differentiate between inflammatory and non-inflammatory i.e. IBD and irritable bowel syndrome (IBS). A negative calprotectin result in a patient without symptoms is reason to avoid en-doscopy while a positive result will triage endoscopy and or intestinal biopsy. Mea-surement of fecal calprotectin helps guide the course of treatment for the physician in the diagnosis of GI patients.

Diagnostic evidence:

LR+ 0 - 2 none LR- > 0.5 none LR+ 2 - 5 weak LR- 0.2 - 0.5 weak LR+ 5 - 10 moderate LR- 0.1 - 0.2 moderate LR+ > 10 high LR- < 0.1 high

LR+ = Sensitivity / (1-Specificity)

LR - = (1-Sensitivity) / Specificity

The high LR+ value of Calprotectin mea-surement shows the conclusive power of a positive test result for inflammation in the intestine.

TF 1 800 661 9993 T 780 702 9500 F 780 438 6595 W somagen.com

THERMO ELIA™ CALPROTECTIN... IS IT INFLAMMATION?

Somagen Diagnostics is your QC partner. Our products include toxicology controls from Utak Laboratories Inc., infectious disease controls from Seracare and Streck Hematology, Chemistry and Immunology controls.

WE ARE CONTROLS

EliA™ Calprotectin—clear IBD and IBS differentiationStool calprotectin measurement is an easy non-invasive first line test which clearly differentiates IBD from IBS and other functional disorders. It has shown to be the most sensitive and specific test and outperforms CRP and ESR.5 The high positive and negative predictive value offers assis-tance in the diagnostic process.5 Moreover, stool calprotectin correlates with disease activity and allows for the prediction of relapses in IBD.6

Advantages with EliA™ Calprotectin:• Clear differentiation

between IBD and IBS

• Early diagnostic guidance

• Completely automated and efficient testing

• Reduces laboratory workload

• Adds to the EliATM gastro panel on Phadia® Laboratory Systems

1. Summerton CB et al (2002). Fecal Calpro-tectin: a marker of inflammation through-out the intestinal tract. Eur J Gastroenterol Hepatol 14: 841-845

2. Roseth AG et al (2004). Normalization of faecal Calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol 39: 1017-1020

3. Roseth AG et al (1997). Assessment of disease activity in ulcerative colitis by faecal Calprotectin, a novel granulocyte marker protein. Digestion 58: 176-80.

4. Vermeire S et al (2006). Laboratory markers in IBD: useful, magic or unneces-sary toys? Gut 55: 426-431

5. Tibble J et al (2000). A simple method for assessing intestinal inflammation in Crohn‘s disease. Gut 47: 506-513

6. Sutherland AD et al (2008). Review of fecal biomarkers in inflammatory bowel disease. Dis Colon Rectum 51: 1283–1291

Utak

UTAK – 100% REAL.

UTAK uses only 100% real human material exclusively for their serum, urine, and whole blood controls. Only UTAK controls will closely and consistently mimic patients’ specimens. UTAK 100% human matrices yield predictable, consistent results. UTAK is renown for their custom toxicology products - If you cannot find a stock product to meet your needs, UTAK will partner with you to manufacture custom controls ac-cording to your exact specifications. You make the choices that fit your needs, UTAK works closely with you through Somagen Diagnostic’s representatives, to produce the controls you require. A 100% real human matrix control from UTAK offers un-rivaled consistency, total flexibility, absolute neutrality important in a 3rd party control and no matrix effect.

SeraCare

WHEN YOU BELIEVE BETTER SCIENCE BEGINS WITH QUALITY BIOLOGICAL MATERIALS. THAT’S SERACARE.

SeraCare has served the global life sciences community, with distinction, for 25 years. They develop and manufacture the highest quality, biologically-based products and offer a broad range of related services, backed by expertise in virology, serology, immunology, and molecular biology. SeraCare develops and manufactures ACCURUN controls, panels, and charac-terized disease state materials for method validation, monitoring, training, trouble-shooting and meeting regulatory require-ments. ACCURUN positive controls target

close to the assay cut-off and are available in multiple series – formulated at a specific concentration for a specific instrument platform.

Streck

CLINICAL LABORATORY PRODUCTS YOU CAN COUNT ON.

Streck manufactures hematology, chemis-try, and immunology products for the clinical laboratory. Recognized worldwide as the leader in cell stabilization, Streck focuses on the development of quality control and diagnostic products to help meet the fast-paced needs of clinical laboratories, with a continued commitment to innovation. Streck’s core technology is cell stabiliza-tion in addition to Hematology controls. Streck also offers immunology, flow cy-tometry, and urinalysis controls. Streck control products test the performance and limits of instruments and reagents. An im-portant characteristic of Streck controls are their stability and physical similarities to real patient samples. Closely resembling patient blood makes it easier for laborato-ries to detect changes in their processes or instruments. Controls are available for most brands of hematology analyzers and come in multiple levels to test the accuracy and sensitivity.

SOMAGEN – YOUR QC PARTNER

Look for exciting new quality control products from Somagen in the coming months.

CONTINUED FROM PAGE 2

SOMAGEN Q2 - WINTER 2012

ESTIMATE GFR WITH GREATER ACCURACY

Past issues of the Somagen Quarterly are available on our website.

VISIT OUR WEBSITE AT SOMAGEN.COM

SOMAGEN QUARTERLY - WINTER 2012

TF 1 800 661 9993 T 780 702 9500 F 780 438 6595 W somagen.com

Since 1997 the National Kidney Foundation (US) has provided evidence-based clinical practice guidelines for all stages of chronic kidney disease (CKD) known as the National Kidney Foundation Kidney Outcome Quality Initiative (NKF KDOQI)™. The KDOQ guide-lines have improved diagnosis and treat-ment of kidney disease throughout the world and are published in the American Journal of Kidney Diseases (AJKD).

Some facts about CKD1:• Chronic kidney disease (CKD) is a major

health concern in Canada, believed to affect more than 2 million Canadians. There are almost 22,000 Canadians on dialysis and ~15,000 living with a functioning renal transplant.

• Manitoba has the highest incidence and prevalence of end-stage renal disease (ESRD) in Canada

• CKD is defined as kidney damage for ≥ 3 months, defined by structural or functional abnormalities, with or without a reduction in glomerular filtration rate (GFR). The National Kidney Foundation has classified CKD into 5 stages for better detection and management of CKD.

• CKD commonly coexists with other diseases such as hypertension, diabetes, and cardiovascular disease (CVD). Early detection of CKD and subsequent management of risk factors for disease progression is paramount.

• In later stages of CKD, patients may develop complications of renal disease. These include anemia, mineral metabolism disorders, malnutrition, cardiomyopathy and chronic fluid overload.

Who should be tested?The NKDEP recommends regular testing of individuals at risk such as those with, diabetes, hypertension, cardiovascular disease and those with a family history.

How is kidney function determined?In order to determine kidney function, the glomerular filtration rate (GFR) is measured. GFR is the rate at which water and dissolved substances are filtered from the blood. Since there is no direct way to measure GFR, it is estimated. To estimate GFR, a sub-stance in the blood that is cleared by the kidney is measured.

Measurement of GFR:The renal marker of choice has been serum Creatinine. Creatinine is a naturally occur-ring substance that is freely filtered by the glomerulus and as relatively minor absorp-tion and secretion by renal tubules. There are however disadvantages to Creatinine as a marker for GFR. Creatinine is affected by multiple non-renal factors including diet, gender, muscle mass and tubular secre-tion which can result in an overstatement of GFR up to 20%. Creatinine has demon-strated poor sensitivity for CKD “creatinine blind range”. Estimation of GFR (eGFR) using the Cockroft-Gault, and the MDRD equation (from the Modification of Diet in Renal Disease clinical study) lack precision. As a result other markers such as Cystatin C are being used to estimate GFR that are freely filtered by the glomerulus and are not affected by age, body mass, gender or race.

Cystatin CCystatin C is a small (13kDa) non-glycosyl-ated protein that is produced at a constant rate by all nucleated cells. Given its small size Cystatin C is freely filtered by the glom-erulus. Cystatin C is not secreted but fully reabsorbed by the renal tubules.

Measurement of GFR using Cystatin C is more sensitive than creatinine. Cystatin C measurements are unaffected by age (>1 year), muscle mass, gender and race—Cystatin C may be used reliably when testing children. Cystatin C is not secreted but is fully absorbed and broken down by renal tubules. As there is no tubular secre-tion of Cystatin C, it is extremely sensitive to small changes in GFR in the earliest stages of CKD. Cystatin C is sensitive to changes in the so-called creatinine blind GFR range (40-70 ml/min/1.73 m2). This enables early detection and treatment of CKD. Cystatin based equations unlike creatinine based

equations are not biased according to GFR. Finally Cystatin C testing enables early de-tection and treatment of CKD in both Type 1 and Type 2 diabetes.

New research has found including Cystatin C and urine albumin-to-creatinine ratio could improve the predictive accuracy of eGFR by creatinine2. A recent study reported that combining a relatively new assay, Cystatin C, with the established creatinine and albumin markers, greatly improved detec-tion of occult CKD as well as assessment of risk for end-stage CKD and death.

Adding Cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease3.

Tosoh AIA The Tosoh Cystatin C assay provides con-sistent results on the AIA-360 and 600II systems. Tosoh AIA systems use reliable dry reagent formats and Unit Dose Test Cup Technology. Assays offer 90 day calibration stability with a time to first result of ~20 minutes.

Unit Dose Test Cup technologySingle, unitized cups use a dry reagent format that requires no pre-mixing, no pre-measuring, no on-board refrigeration and no waste. Dry reagent format ensures cali-bration stability of up to 90 days for most assays. Reagents have a one year shelf life from date of manufacture. The AIA test cups and trays are labeled with code and lot number for automated scheduling and inventory management. An extensive test menu provides a wide range of immunoas-say tests.

Please contact your Somagen Representa-tive for more information on Cystatin C and the Tosoh AIA instruments.

REFERENCES1. Excerpt from kidneyhealth.ca

2. Clinical Laboratory Strategies: May 26, 2011; Improving Detection Of Chronic Kidney Disease; Bill Malone

3. Detection Of Chronic Kidney Disease With Creatinine, Cystatin C, And Urine Albumin-to-creatinine Ratio And Association With Progression To End-stage Renal Disease And Mortality

JAMA, April 20, 2011—Vol 305, No. 15