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MICROALBUMIN TESTING IN THE TREATMENT AND MANAGEMENT OF DIABETES
| Author: Robert Janetschek - MS, MT (ASCP) |
| Article Date: 10/1/2007 |
Diabetes is widely recognized as one of the leading causes of death and disability in the United States. Just five years ago, diabetes cost the United States in excess of $132 billion Ð indirect costs, including disability payments, time lost from work and premature death, totaled more than $40 billion; direct medical costs for diabetes care, including hospitalizations, medical care and treatment supplies, totaled greater than $92 billion. From 1980 through 2004, the number of Americans diagnosed with diabetes more than doubled from 5.8 million to 14.7 million, with people aged 65 years or older accounting for almost 40% of the population with diabetes. Diabetes is associated with long-term complications that affect almost every part of the body. Uncontrolled diabetes leads to, among others, kidney failure, blindness, amputations, nerve damage, pregnancy complications (including birth defects), and cardiovascular disease.1
Regarding the latter, cardiovascular disease affects millions of adults with diabetes and is a major cause of morbidity and mortality among persons with diabetes, but surprisingly, diabetes is likely to be underreported as the underlying cause of death on death certificates. In 2003, 5.2 million persons aged 35 years and older with diabetes reported being diagnosed with a cardiovascular disease condition (i.e., coronary heart disease, stroke, or other heart condition). Among this group of 5.2 million adults, 3.5 million reported being diagnosed with coronary heart disease (self-reported coronary heart disease, angina, or heart attack) and 1.5 million reported being diagnosed with stroke. Heart disease affects more Americans than any other illness and is the number one cause of mortality among women.2
Alarming numbers, with the most obvious questions being what can, or is being done to curtail this? Fortunately, much is already in the works, especially in the clinical laboratory testing environment. The American Diabetes Association has made great strides with its frequent publication of Standards of Medical Care in Diabetes, which specifically lists and advocates the use of particular diagnostic laboratory tests to aid in the prevention and management of diabetes complications, as well as being vital components of a comprehensive diabetes evaluation. These tests include:
Hemoglobin A1c.
Fasting lipid profile (includes Total Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides).
Serum Creatinine and calculated glomerular filtration rate (GFR) in adults; with an additional check with children if proteinuria is present.
Thyroid-stimulating hormone (TSH) in all Type I diabetic patients and in Type II if clinically indicated.
Urinalysis for ketones, protein, sediment, etc.
Liver function tests, with further evaluation for fatty liver, or hepatitis, if abnormal.
Annual test for microalbuminuria in Type I diabetic patients who have had diabetes for at least 5 years and in all patients with Type II diabetes; with strong advocacy of screening of pubertal children with a known family history of diabetes, or disposition toward the disease, prior to onset of diabetes and before five years of initial diagnosis.3
For those unfamiliar with microalbuminuria, the presence of protein in urine has long been recognized as an indicator of disease. With the diabetic patient however, progressive proteinuria is a strong indicator of future evident nephropathy. Proteinuria associated with nephrotic syndromes may be tubular or glomerular in origin. Tubular proteinuria results in excretions of the lower molecular weight proteins, which are normally filtered and reabsorbed, such as transferrin and α1-microglobulin. In glomerular proteinuria, albumin becomes the predominant protein, while other macromolecules, such as IgA and IgG and their light chains, may appear in normal concentrations.
Diabetic nephropathy is a clinical syndrome characterized by hypertension and developing renal insufficiency, which results in albuminuria. With the onset of diabetic nephropathy, renal function rapidly deteriorates and renal insufficiency progresses. Prior to end-state renal failure, there is a period of increased urinary albumin excretion which can not be detected by the standard, traditional urine dipstick methods. Unfortunately, these conventional urine dipsticks are insensitive to the subclinical increases in urinary albumin excretion, as a range of 20 to 200 µg/minute (30 to 300 mg/24 hours) of increased urinary albumin excretion defines microalbuminuria. The degree of microalbuminuria is also predictive of the progression to clinical proteinuria in both Type I and II diabetes. Moreover, patients with microalbuminuria also display increased risk for developing proliferative retinopathy than patients with normal urinary albumin excretion. 4-7
In response to this critical clinical requirement, Diagnostic Chemicals Limited (PEI, Canada) has introduced the ImmunoDip¨ assay for the detection of microalbumin, a significantly improved urine dip-stick method (Figure 1). ImmunoDip measures the concentration of urinary albumin using an immunochromatographic test device containing specific monoclonal antibody against human albumin. Contained within the device are labeled antibody conjugate, immobilized antigens and immobilized antibody. During testing, albumin present in the urine sample binds with blue colored latex beads present in the test device and are carried up the test device by lateral flow.
The test strip has human albumin fixed in the lower of two bands on the strip and at low levels of albumin in the sample, the latex beads bind to the band of albumin, producing a blue colored band in the lower half of the test window. The test window also has a second band that can also bind the blue colored latex beads, even if they have reacted with albumin in the urine. When there is a low concentration of albumin in the urine, the majority of beads will bind to the lower band. However, some of the beads will react with the small amount of albumin present and these beads will pass through the lower band, but will be bound at the upper, producing a second blue colored band. As the concentration of albumin in the urine increases, more beads pass through the first band and are bound by the second band. After the completion of the test, the darkness, or intensity, of the two blue bands in the test window is compared. If the band in the upper portion of the test window is lighter than, or equal to the lower band, the test is negative, meaning there is a normal level of albumin (less than18 mg/L) in the test sample. If the band in the upper half of the test window is darker than the lower band, the test is positive, meaning there is higher concentration of albumin in the test urine sample than normal (greater than 18 mg/L).
Aside from the many technical advancements associated with ImmunoDip, the assay also offers testing facilities several other important benefits. For example, the assay is a self-contained testing device, with a built-in control, that utilizes a very simple and easy-to-use four (4) step test procedure which generates test results in only three (3) minutes. This simplicity and versatility allows the assay to be used in virtually any clinical setting Ð 24 hours a day, 7 days a week. Second, and depending on the format used (either the CLIA waived, or moderately complex rated), the assay allows generation of either qualitative or semi-quantitative test results, with no significant cross-reactivity interference from common medications and other human proteins. Third, the assay is extremely cost-effective, generating accurate, reliable test results without the need for expensive instrumentation, biochemical reagents and ancillary supporting products. Last, ImmunoDip has displayed a documented history of testing performance in some of the most demanding clinical environments. In published reports from independent evaluations, test reviewerÕs comments have included ÒImmunoDip is an excellent screening tool for microalbuminuria.Ó8; Òthe device is simple to use and the results easy to interpret.Ó9; and that the test itself Òmay be a useful and valid method for the screening of albuminuria.'10
In conclusion, the early detection of microalbuminuria is critical to initiate the necessary treatment to slow, or even prevent, the development of diabetic nephropathy. With sufficient warning, physicians can easily intervene in the progression of renal damage through such available testing options as ImmunoDip assay for the detection of urinary albumin. DCLÕs ImmunoDip microalbumin assay benefits the needs of medical laboratory professionals, physicians and, most importantly, diabetic patients alike.
____________________________________
REFERENCES
American Diabetes Association; www.diabetes.org
American Heart Association; www.americanheart.org
American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care, Vol. 29, Sup. 1; January 2006, S4-S42
Viberti GC, Hill RD, et al. Microalbuminuria as a Predictor of Clinical Nephropathy in Insulin Dependent Diabetes Mellitus. Lancet 1982; i:1430-1432.
Mathiesen ER, Ronn B, et al. Relationship Between Blood Pressure and Urinary Albumin Excretion in Development of Microalbuminuria. Diabetes 1990; 39:245-249.
Beckman Instruments Technical Bulletin 9010-IDf, Renal Disease, 1995.
Mogensen, C. E. & Christensen, C. K. Predicting Diabetic Nephropathy in Insulin-Dependent Patients. N Engl J Med; 1984, 311:89-93.
HYPERLINK 'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15087587&query_hl=1&itool=pubmed_DocSum' Davidson MB, Bazargan M, et. al.; ImmunoDip: An Improved Screening Method for Microalbuminuria. Am J Nephrol; 2004 May-Jun, 24(3):284-8.
Burtonwood C, Piggott C, Halloran S; Point of Care Devices for Detection and Semi-Quantitation of Microalbuminuria. Medicines and Healthcare Products Regulatory Agency (MHRA) Report 04898; October 2004, 35-42.
Pfab T, Franz U, et al. Rapid Immunochromatographic Strip Test for the Detection of Albuminuria and Brief Literature Review on Albuminuria Screening. Eur J Med Res (2006); 11: 3-6.
Figure 1 - ImmunoDip¨ Urinary Albumin Assay from Diagnostic Chemicals Limited
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Regarding the latter, cardiovascular disease affects millions of adults with diabetes and is a major cause of morbidity and mortality among persons with diabetes, but surprisingly, diabetes is likely to be underreported as the underlying cause of death on death certificates. In 2003, 5.2 million persons aged 35 years and older with diabetes reported being diagnosed with a cardiovascular disease condition (i.e., coronary heart disease, stroke, or other heart condition). Among this group of 5.2 million adults, 3.5 million reported being diagnosed with coronary heart disease (self-reported coronary heart disease, angina, or heart attack) and 1.5 million reported being diagnosed with stroke. Heart disease affects more Americans than any other illness and is the number one cause of mortality among women.2
Alarming numbers, with the most obvious questions being what can, or is being done to curtail this? Fortunately, much is already in the works, especially in the clinical laboratory testing environment. The American Diabetes Association has made great strides with its frequent publication of Standards of Medical Care in Diabetes, which specifically lists and advocates the use of particular diagnostic laboratory tests to aid in the prevention and management of diabetes complications, as well as being vital components of a comprehensive diabetes evaluation. These tests include:
Hemoglobin A1c.
Fasting lipid profile (includes Total Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides).
Serum Creatinine and calculated glomerular filtration rate (GFR) in adults; with an additional check with children if proteinuria is present.
Thyroid-stimulating hormone (TSH) in all Type I diabetic patients and in Type II if clinically indicated.
Urinalysis for ketones, protein, sediment, etc.
Liver function tests, with further evaluation for fatty liver, or hepatitis, if abnormal.
Annual test for microalbuminuria in Type I diabetic patients who have had diabetes for at least 5 years and in all patients with Type II diabetes; with strong advocacy of screening of pubertal children with a known family history of diabetes, or disposition toward the disease, prior to onset of diabetes and before five years of initial diagnosis.3
For those unfamiliar with microalbuminuria, the presence of protein in urine has long been recognized as an indicator of disease. With the diabetic patient however, progressive proteinuria is a strong indicator of future evident nephropathy. Proteinuria associated with nephrotic syndromes may be tubular or glomerular in origin. Tubular proteinuria results in excretions of the lower molecular weight proteins, which are normally filtered and reabsorbed, such as transferrin and α1-microglobulin. In glomerular proteinuria, albumin becomes the predominant protein, while other macromolecules, such as IgA and IgG and their light chains, may appear in normal concentrations.
Diabetic nephropathy is a clinical syndrome characterized by hypertension and developing renal insufficiency, which results in albuminuria. With the onset of diabetic nephropathy, renal function rapidly deteriorates and renal insufficiency progresses. Prior to end-state renal failure, there is a period of increased urinary albumin excretion which can not be detected by the standard, traditional urine dipstick methods. Unfortunately, these conventional urine dipsticks are insensitive to the subclinical increases in urinary albumin excretion, as a range of 20 to 200 µg/minute (30 to 300 mg/24 hours) of increased urinary albumin excretion defines microalbuminuria. The degree of microalbuminuria is also predictive of the progression to clinical proteinuria in both Type I and II diabetes. Moreover, patients with microalbuminuria also display increased risk for developing proliferative retinopathy than patients with normal urinary albumin excretion. 4-7
In response to this critical clinical requirement, Diagnostic Chemicals Limited (PEI, Canada) has introduced the ImmunoDip¨ assay for the detection of microalbumin, a significantly improved urine dip-stick method (Figure 1). ImmunoDip measures the concentration of urinary albumin using an immunochromatographic test device containing specific monoclonal antibody against human albumin. Contained within the device are labeled antibody conjugate, immobilized antigens and immobilized antibody. During testing, albumin present in the urine sample binds with blue colored latex beads present in the test device and are carried up the test device by lateral flow.
The test strip has human albumin fixed in the lower of two bands on the strip and at low levels of albumin in the sample, the latex beads bind to the band of albumin, producing a blue colored band in the lower half of the test window. The test window also has a second band that can also bind the blue colored latex beads, even if they have reacted with albumin in the urine. When there is a low concentration of albumin in the urine, the majority of beads will bind to the lower band. However, some of the beads will react with the small amount of albumin present and these beads will pass through the lower band, but will be bound at the upper, producing a second blue colored band. As the concentration of albumin in the urine increases, more beads pass through the first band and are bound by the second band. After the completion of the test, the darkness, or intensity, of the two blue bands in the test window is compared. If the band in the upper portion of the test window is lighter than, or equal to the lower band, the test is negative, meaning there is a normal level of albumin (less than18 mg/L) in the test sample. If the band in the upper half of the test window is darker than the lower band, the test is positive, meaning there is higher concentration of albumin in the test urine sample than normal (greater than 18 mg/L).
Aside from the many technical advancements associated with ImmunoDip, the assay also offers testing facilities several other important benefits. For example, the assay is a self-contained testing device, with a built-in control, that utilizes a very simple and easy-to-use four (4) step test procedure which generates test results in only three (3) minutes. This simplicity and versatility allows the assay to be used in virtually any clinical setting Ð 24 hours a day, 7 days a week. Second, and depending on the format used (either the CLIA waived, or moderately complex rated), the assay allows generation of either qualitative or semi-quantitative test results, with no significant cross-reactivity interference from common medications and other human proteins. Third, the assay is extremely cost-effective, generating accurate, reliable test results without the need for expensive instrumentation, biochemical reagents and ancillary supporting products. Last, ImmunoDip has displayed a documented history of testing performance in some of the most demanding clinical environments. In published reports from independent evaluations, test reviewerÕs comments have included ÒImmunoDip is an excellent screening tool for microalbuminuria.Ó8; Òthe device is simple to use and the results easy to interpret.Ó9; and that the test itself Òmay be a useful and valid method for the screening of albuminuria.'10
In conclusion, the early detection of microalbuminuria is critical to initiate the necessary treatment to slow, or even prevent, the development of diabetic nephropathy. With sufficient warning, physicians can easily intervene in the progression of renal damage through such available testing options as ImmunoDip assay for the detection of urinary albumin. DCLÕs ImmunoDip microalbumin assay benefits the needs of medical laboratory professionals, physicians and, most importantly, diabetic patients alike.
____________________________________
REFERENCES
American Diabetes Association; www.diabetes.org
American Heart Association; www.americanheart.org
American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care, Vol. 29, Sup. 1; January 2006, S4-S42
Viberti GC, Hill RD, et al. Microalbuminuria as a Predictor of Clinical Nephropathy in Insulin Dependent Diabetes Mellitus. Lancet 1982; i:1430-1432.
Mathiesen ER, Ronn B, et al. Relationship Between Blood Pressure and Urinary Albumin Excretion in Development of Microalbuminuria. Diabetes 1990; 39:245-249.
Beckman Instruments Technical Bulletin 9010-IDf, Renal Disease, 1995.
Mogensen, C. E. & Christensen, C. K. Predicting Diabetic Nephropathy in Insulin-Dependent Patients. N Engl J Med; 1984, 311:89-93.
HYPERLINK 'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15087587&query_hl=1&itool=pubmed_DocSum' Davidson MB, Bazargan M, et. al.; ImmunoDip: An Improved Screening Method for Microalbuminuria. Am J Nephrol; 2004 May-Jun, 24(3):284-8.
Burtonwood C, Piggott C, Halloran S; Point of Care Devices for Detection and Semi-Quantitation of Microalbuminuria. Medicines and Healthcare Products Regulatory Agency (MHRA) Report 04898; October 2004, 35-42.
Pfab T, Franz U, et al. Rapid Immunochromatographic Strip Test for the Detection of Albuminuria and Brief Literature Review on Albuminuria Screening. Eur J Med Res (2006); 11: 3-6.
Figure 1 - ImmunoDip¨ Urinary Albumin Assay from Diagnostic Chemicals Limited
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