The presence of increased amounts of protein (albumin) in urine, or microalbuminuria, is a key indicator of kidney function and is routinely used to monitor the health of patients with diabetes mellitus. This article stresses the importance of routine testing for urine albumin to assess kidney function as an aspect of overall patient health. It also highlights the significance of performing automated complementary urinalysis tests when kidney damage is detected.
The albumin-to-creatinine ratio
Albumin circulates throughout the body at high concentrations and is normally filtered by the kidney; however, in some disease states the kidney allows the protein to pass and be excreted into urine. The amount of albumin in a urine sample can be easily measured both quantitatively and qualitatively with a number of point-of-care techniques. Urine strips can be used to estimate both total protein and specifically albumin. Quantitative immunoassays are able to give accurate and specific measures of the protein.
Historically, albumin secretion was monitored over a 24-hour time period to allow calculation of albumin excretion rates (AER). This would account for fluctuations in urine concentration throughout the day. The introduction of a simultaneous creatinine measurement permits normalization of albumin concentration and requires only a single spot test to give the albumin-creatinine ratio (ACR). Creatinine is a degradation product that also circulates throughout the body, but is not filtered by the kidney and is normally excreted as waste.
There are a number of tests available for urine creatinine estimation, the majority of which involve chemical or enzymatic reactions. An ACR measurement is reported in mg albumin/g creatinine and is widely accepted as an indicator of kidney function. Currently the National Kidney Foundation defines an ACR range from 30 to 300 mg/g as above normal, and multiple tests in this range over a three-month period suggest a problem.1
Estimation of glomerular filtration rate
Another key measurement in the identification of microalbuminuria is the estimated glomerular filtration rate (eGFR). The number is estimated from a measure of serum creatinine and other factors including age, weight, and sex. Healthy kidney function is marked by the ability to excrete creatinine into the urine; therefore, a typical eGFR of 60 or more is considered healthy, while a value below 60 may be a sign of decreased function and will require further prolonged testing.2
Typically, both ACR and eGFR numbers are collected; however, eGFR has a few drawbacks. Primarily, the need for measurement of a whole blood creatinine as well as the choice of an appropriate equation to generate the final estimate makes this a somewhat more complicated test. Therefore, for routine screening in a point-of-care setting, urine ACR may be the most beneficial.
Kidney disease and population health management
Yearly urine ACR tests are recommended for patients with diabetes to identify progression of kidney failure (Figure 1).3 More than 30 million Americans have diabetes, with 1.5 million new cases diagnosed every year.4 The prevalence of diabetes is increasing worldwide, with 422 million cases as of 2014.5
It is estimated that 10 percent of the global population is affected by chronic kidney disease (CKD).6 Between 1990 and 2010, kidney disease became one of the fastest-growing causes of death in the world, second only to HIV/AIDS.6 Prompt detection is crucial in the early stages of kidney disease, since there are typically no overt signs or symptoms. If CKD is detected early and managed appropriately, the deterioration in kidney function can be slowed and the risk of associated cardiovascular complications reduced.7
The impact of chronic kidney disease extends beyond just a diminished quality of life for those affected by the disease; it also represents more than $1 trillion in healthcare costs over the next decade.8 In this context, it is safe to assume that urine ACR tests will remain an essential resource for healthcare providers and that detection of microalbuminuria is critical for assessing potential complications of the disease.
Complementing ACR with automated urinalysis
Managing chronic diseases such as diabetes will be a major ongoing concern for healthcare providers worldwide. There is a need for tests to allow efficient and accurate diagnoses. As described above, urine ACR is a great predictor of kidney function, and poor kidney function is an indicator of significant disease. Poor kidney function values will very likely lead to more tests needing to be performed. Urine dipstick analysis allows for a number of tests to be run at once on one sample. For example, complementary urine tests can aid in assessing carbohydrate metabolism (urine glucose or ketone) or potential infections (leuckocytes).
Additionally, urine sediment analysis provides information not available from urine ACR or urine dipstick testing. In one study that analyzed urinalysis results from patients at multiple institutions, manual sediment examination (usually triggered by an abnormal dipstick test result) provided new information 66 percent of the time.9 Urine sediment analysis allows the identification of pathological casts that are not identified by other urinalysis methods, in some cases allowing earlier diagnosis and treatment of kidney disease.10
Urine sediment analysis has historically been performed manually, but manual analysis is time-consuming and difficult to standardize. Urine dipstick testing has been automated, removing user variation and allowing high-throughput testing that allows more efficient use of laboratory personnel. In recent years, automated methods of sediment analysis have also become available and are likely to be of increasing importance in the future.
Urinalysis is one of the oldest and most established methods of medical diagnostics and remains a simple and rapid means of monitoring patient health. The ability to assess kidney function through urine ACR tests is critical as it may indicate serious complications that require further investigation. It can also potentially be cost-saving as it can be used to screen for good kidney function, thus avoiding other unnecessary tests. Certainly the continuing burden of chronic disease and rising healthcare costs give every reason to think that urinalysis will continue to be critical in the future.
- The National Kidney Foundation. ACR. https://www.kidney.org/kidneydisease/siemens_hcp_acr .
- The National Kidney Foundation. Glomerular filtration rate (GFR). https://www.kidney.org/atoz/content/gfr.
- The National Kidney Foundation. Diabetes and kidney disease (Stages 1-4). https://www.kidney.org/atoz/content/Diabetes-and-Kidney-Disease-Stages1-4.
- American Diabetes Association. Statistics. http://www.diabetes.org/diabetes-basics/statistics/.
- World Health Organization. Factsheets. http://www.who.int/mediacentre/factsheets/fs312/en/.
- The Nation Kidney Foundation. Global facts about kidney disease. https://www.kidney.org/kidneydisease/global-facts-about-kidney-disease.
- World Kidney Day: Chronic kidney disease. http://www.worldkidneyday.org/faqs/chronic-kidney-disease/.
- Scottish Kidney Federation. Chronic kidney disease. http://scotskidneyfederation.org/ckd-information.html.
- Tworek JA, Wilkinson DS, Walsh MK. The rate of manual microscopic examination of urine sediment: a College of American Pathologists Q-Probes study of 11,243 urinalysis tests from 88 institutions, Arch Pathol Lab Med. 2008:132(12):1868-1873.
- Verdesca S, Brambilla C, Garigali G, Croci MD, Messa P, Fogazzi G. How a skillful and motivated urinary sediment examination can save the kidneys. Nephrol Dial Transplant. 2007;22(6):1778-1781.
Julie Chaney, PhD, and Jeffrey Mayfield, PhD, both serve as Senior Scientists for