What Are Biomarkers?
Biomarkers are other biological molecules that are found in blood, other fluids in the body, or tissues. It is a sign of normal functioning, an abnormal process, or a condition or disease. It is used as a marker for diagnosis and further screening of the disease. Biological markers can be used to see how the body responds to certain treatments. Every biological system, such as the cardiovascular, metabolic, or immune systems, has its own specific biomarker. Many of these biomarkers can be easily measured and can be found in routine medical examinations.
The characteristics of a biomarker must include-easy and safe to measure, cost-efficient can be modified with treatment, and should be consistent among gender and ethnic groups. Biomarkers predict health conditions and provide a detailed picture of the health status of a person and whether a diagnosis needs to be made. The assessment of a typical biomarker helps in the development of therapies that can target the biomarker. Examples of biomarkers may include assessment of the blood pressure, heart rate, fasting glucose levels, postprandial glucose levels, triglycerides, cholesterol levels, creatinine, and kidney injury molecule-1.
What Are the Biomarkers of Kidney Function?
Chronic kidney disease involves a long latent period, making diagnosing, evaluating, and treating the disease difficult. Therefore, the diagnosis and treatment are based mainly on the biomarkers that assess kidney function. The markers for assessment of kidney function include -
-
Glomerular Filtration Rate (GFR ) - GFR is the ideal marker of kidney function. It is time-consuming, so GFR is usually measured from equations containing biological markers such as serum creatinine and cystatin.
-
Serum Creatinine - Creatinine is a chemical compound that is produced in the muscles from energy-producing processes. Healthy kidneys filter out creatinine from the blood. However, kidney function impairment prevents the excretion of creatinine, which leads to an increase in levels of serum creatinine and can be used as a biomarker of kidney function.
-
Cystatin - Cystatin is a protein present inside the blood produced by the cells of the body. The level of cystatin is maintained well by the kidneys. The level of cystatin in the blood increases only when there is a moderate to a severe reduction in glomerular filtration rate (GFR). Increased levels of cystatin in serum indicate the improper functioning of the kidneys.
-
Albuminuria - Albumin is a protein that is found in the blood. Healthy kidneys do not let any albumin pass through it into the urine. Albuminuria occurs when the kidneys are unable to reabsorb the albumin back into the blood. This leads to albuminuria, the presence of albumin in the urine. It is hence used to test kidney functioning.
-
Urine Albumin to Creatinine Ratio - It is also known as the urine microalbumin ratio. It helps to identify kidney disease that occurs as a complication of diabetes mellitus. A slightly raised albumin creatinine ratio indicates early-stage kidney disease, a high level indicates more severe kidney disease, and a low albumin creatinine ratio indicates normal functioning of the kidneys. Therefore it becomes very necessary for a person suffering from diabetes to measure the albumin creatinine ratio more frequently, once or twice a year.
-
Kidney Injury Molecule-1- Kidney injury molecule-1 is a novel marker of the proximal tubule injury of the kidney. It is a transformer in protein that is regulated in the proximal tubule of the kidneys and is used to evaluate acute renal failure or acute renal tubular injury. The presence of kidney injury molecule-1 in urine can be detected by immunoassay. The KIM-1 urine soluble molecule can be detected in patients with acute tubular necrosis and serves as a useful biomarker for proximal tubule injury and helps in the diagnosis of the disease.
-
Neutrophil Gelatinase-Associated Lipocalin (NGAL) - Neutrophil gelatinase-associated lipocalin is a protein produced by the injured epithelium of the nephron. A nephron is the filtering unit of the kidney. NGAL is specially produced in the damaged nephron and is released into the blood and urine. Unlike creatinine, which measures kidney function, NGAL is a biomarker responsive to tissue stress, damage, and nephron injury. NGAL is an earlier marker for kidney injury compared to serum creatinine.
-
Blood Urea Nitrogen (BUN) - Blood urea nitrogen increases as the GFR decreases. It is less valuable than the serum creatinine levels as the BUN changes independently of the GFR. The urea production is not stable. It increases with a protein-rich diet or tissue damage such as hemorrhage, muscle trauma, or steroid administration and decreases with a low protein diet and liver failure without affecting the GFR.
When Are Biomarkers of the Kidney Function Needs to Be Assessed?
-
Estimation of the Kidney Function - Measurement of the kidney function is done using serum creatinine concentration, blood urea nitrogen level, and analysis of the urine. However, recent studies have shown that these biomarkers are not suitable for detecting kidney disease at an early stage. Therefore the diagnosis, classification, and staging of chronic kidney disease can be made by the GFR along with the serum creatinine, blood urea nitrogen, and other biomarkers. Different equations such as the creatinine clearance equation, chronic kidney disease-epidemiology collaboration equation, cystatin C and combined cystatin C and creatinine equation, blood urea nitrogen, and beta2-microglobulin estimation are used in the assessment of kidney function.
-
Estimation of Kidney Damage - Kidney damage or improper functioning of the kidneys can be assessed by using biomarkers. The biomarkers in kidney damage include albuminuria, estimated glomerular filtration rate (eGFR), cystatin C, serum creatinine, and urine albumin to creatinine ratio. The combination of biomarkers such as combining albuminuria with eGFR, eGFR creatinine, cystatin C, and urine albumin to creatinine ratio improves the risk reduction compared to the eGFR alone. Although these biomarkers appear after the damage has occurred or not be present in other types of kidney damage such as interstitial disease and hypertensive kidney disease. New biomarkers such as NGAL (Neutrophil gelatinase-associated lipocalin) and KIM1 (Kidney injury molecule-1) are specific to certain types of kidney injury. Serum creatinine is widely used to screen and diagnose kidney disease; however, it has certain limitations and should be used only in estimating calculations.
Conclusion :
Biomarkers play a very important role in improving the diagnosis of the disease, biomedical research, and drug development. Clinical assessment of conditions such as blood pressure or cholesterol level can be made using biomarkers to predict the health status and plan therapeutic intervention. Health prediction, disease conditions, cancer detection, and drug development can be made using biomarkers. For example, certain biomarkers such as kidney molecule-1 and neutrophil gelatinase-associated lipocalin are the specific markers of acute kidney injury, including the proximal tubule and the damage to the epithelium of the nephron, respectively.
