Facilitating kidney function testing through the use of reagents applicable to a variety of automated systems

The kidneys play an important role in homeostasis, they regulate the amount of water and salts present in the body by filtering blood through the nephrons. Waste products are filtered out and eliminated from the body in the urine, which is made up of the excess water, salts and waste products.

When the kidneys are not functioning efficiently, waste products and fluids begin to accumulate instead of being excreted which can cause serious health problems. Furthermore, kidney disorders can often develop and advance over a period of time without showing any signs; alternatively, symptoms are not recognized as being associated with kidney problems. Kidney function testing is therefore relevant for diagnosing and monitoring disease and assists in the development of appropriate treatment plans. Laboratory automation facilitates the efficiency and productivity of clinical laboratories. The determination of parameters related to kidney function by using tests  incorporating reagents applicable to a variety of automated analysers facilitates clinical effectiveness and patient outcomes when managed by qualified laboratory professionals.

Kidney function assessment
Many conditions can affect the ability of the kidneys to carry out their vital functions. Some conditions can lead to a rapid (acute) decline in kidney function; other conditions lead to a gradual (chronic) decline. A number of clinical laboratory tests in blood and urine can be used to assess renal function. The unit measure of kidney function is the glomerular filtration rate (GFR), which can be defined as the volume of plasma cleared of an ideal substance –freely filtered at the glomerulus and neither secreted nor reabsorbed by the renal tubules- per unit of time. The normal range is 80-120 ml/min. Measuring this rate is a laborious process. Creatinine is the closest to an ideal endogenous substance for measuring GFR.[1,2] Creatinine is derived from creatine and creatine phosphate in muscle tissue and is defined as a nitrogenous waste product. Creatinine is not reutilized but is excreted from the body in the urine via the kidney. As a consequence of the way in which creatinine is excreted by the kidney, its measurement is used almost exclusively in the assessment of kidney function. 

Urea, a byproduct of protein metabolism, is produced in the liver and then is filtered from the blood and excreted in the urine by the kidneys. The blood urea nitrogen test (BUN) measures the amount of nitrogen contained in the urea, high levels can indicate kidney dysfunction. As these levels are also affected by protein intake and liver function, this test is usually done together with a blood creatinine test.
Cystatin C is a small cysteine proteinase inhibitor that is steadily produced by all nucleated cells. The small molecular weight of cystatin C allows it to be freely filtered by the glomerular membrane and therefore cystatin C levels in the blood are indicative of a normal or impaired GFR. Levels of cystatin C in serum/plasma are almost entirely dependent on GFR.[3]

Other tests for the measurement of other parameters regulated in part by the kidneys can also be useful for the evaluation of kidney function; these tests include electrolytes (sodium, potassium, chloride, bicarbonate), protein, uric acid and glucose:

• Electrolyte balance is essential for the normal function of cells and organs. Renal problems can be the cause of increased (hypernatremia) or decreased (hyponatremia) sodium concentration in blood. Potassium is normally excreted by the kidneys, elevated concentrations of potassium (hyperkalemia) can be an indicator of reduced renal function and potassium testing is also useful in the monitoring of patients receiving dialysis treatment. Increased (hyperchloremia) or decreased (hypochloremia) chloride concentrations can be a consequence of certain kidney diseases.  The bicarbonate test is performed to monitor the acidity of the blood and other body fluids. Disruptions in the normal level of bicarbonate may be seen in kidney diseases.

• The determination of total urinary protein is valuable in the evaluation of kidney function as healthy kidneys filter all the proteins and then return them to the bloodstream whereas damaged kidneys have diminished filtering ability and protein is therefore found in the urine.

• Albumin is one of the major plasma proteins and in normal circumstances, is too large to cross the renal glomerular basement membrane. When damage occurs, the permeability of this membrane can change and albumin is then able to enter the urine. Albumin excretion rate of 20-200 µg/min is defined as microalbuminuria.[4]

• Uric acid is a waste product excreted by the kidneys. Overproduction or reduced excretion of uric acid causes elevated concentrations of this molecule in the blood (hyperuricemia) or the urine (uricosuria). Increased concentrations of uric acid can form crystals in the joints (leading to joint inflammation and pain characteristic of gout) or in the  kidneys (kidney stones that can cause kidney damage).

• Abnormalities in glucose metabolism have been reported in patients with renal failure.[5]

Application of kidney function tests to automated systems
In clinical settings the application of tests for the determination of parameters related to kidney function to automated systems, facilitates clinical effectiveness and productivity. There are currently tests available for the determination of creatinine, BUN, cystatin C, electrolytes, protein, uric acid and glucose among others. If a variety of these tests could be applied to one system, the result output for each system would increase, which would maximize efficiency. The use of tests incorporating reagents applicable to a variety of automated analysers is beneficial as it increases the testing capacity of one system. This is further enhanced by the analyser’s capability to employ different methodologies with different reagents. The combination of automation and the use of stable, high performance  reagents, lead to optimal analytical performance, extensive measuring ranges to ensure detection of abnormal values and reduced interference to produce more accurate results. For instance, a study using a creatinine test reported no interference with bilirubin and metamizol.[6]
The application of other kidney function related tests to studies in patients with nephrotic syndrome, chronic liver diseases and diabetes have also been reported.[7-8]
The automation of laboratory testing still requires qualified laboratory professionals for the evaluation of the results but reduces errors, staffing concerns and safety issues. This facilitates the diagnosis and the monitoring of kidney function, which is of great importance in clinical practice and in research.

Conclusion
The kidneys are the body’s natural filtration system and perform many vital functions. Kidney function tests is a collective term for a variety of individual tests and procedures for the evaluation of how well kidneys are functioning. The determination of parameters related to kidney function (i.e.creatinine, BUN, cystatin C, electrolytes, protein, uric acid, glucose)  by using tests incorporating reagents applicable to a variety of automated analysers, increases the testing capacity of the systems and facilitates clinical effectiveness and patient outcomes when managed by qualified laboratory professionals.

References
1. Berger A. Renal function – and how to assess it.  BMJ. 2000; 321: 1444.
2. Traynor J, Mactier R, Geddes CC, Fox JG. How to measure renal function in clinical practice. BMJ. 2006; 333 (7571): 733-737.
3. Laterza OF, Price CP, Scott MG. Cystatin C: an improved estimator of glomerular filtration rate? Clin. Chem. 2002; 48(5): 699-707.
4. Kirby M. Screening for microalbuminuria. The British Journal of Diabetes and Vascular Disease. 2002; 2(2): 106-109.
5. Sechi LA, Catena C, Zingaro L., Melis A, De Marchi S. Abnormalities of glucose metabolism in patients with early renal failure. Diabetes. 2002; 51: 1226-1232.
6. Harmonien AP. Bilirubin and metamizol do not interfere with the Randox enzymatic creatinine test. An evaluation of a new enzymatic creatinine determination method. Eur. J. Clin. Chem. Clin. Biochem. 1996; 34(12): 975-976.
7. Mula-Abed W-AS and Hanna BE. Measurement of serum fructosamine as an index of glycated protein in patients with nephrotic syndrome and chronic liver diseases. Bahrain Medical Bulletin 2001; 23(4).
8. Hirnerova E, Krahulec B, Strbova L, Stecova A, Dekret J, Hajovska A, Ch A Dukat A. Effect of vitamin E supplementation on microalbuminuria, lipid peroxidation and blood prostaglandins in diabetic patients. Bratisl. Lek. Listy 2004; 105(12): 408-413.

Author
María Luz Rodríguez
Randox Laboratories Limited,
55 Diamond Road, Crumlin,
County Antrim, N. Ireland, BT29 4QY,
United Kingdom