Kidney Markers/Urinalysis
What Are The Kidney Function?
Kidneys are an organ that serves many important functions to keep you healthy.
Filtration of Blood: One of the major roles of kidneys is to filter the blood to avoid contamination and excess fluids. The excretion of all this fluid and waste is called urine.
Regulation of Electrolytes: Kidneys regulate electrolytes including sodium, potassium, and phosphate which are necessary for nerve and muscle activity.
Acid-Base Balance: They help regulate the body's pH level by excreting hydrogen ions and reabsorbing bicarbonate from urine.
Blood Pressure Regulation: The kidneys secrete an enzyme called renin that regulates blood pressure.
Erythropoiesis: Kidneys produce erythropoietin, a hormone that stimulates the production of red blood cells in the bone marrow.
Metabolism of Vitamin D: They are involved in converting vitamin D into its active form, which is essential for healthy bones and calcium balance.
How the Kidney Works?
The kidneys function by filtering blood through nephrons, which are the functional units of the kidneys consisting of a glomerulus and a tubule. Blood enters the kidneys via the renal artery, eventually reaching the nephrons through branching smaller blood vessels. During glomerular filtration, blood is pushed through the glomerulus, a tiny network of blood vessels that acts as a filter, permitting the passage of water and small molecules while retaining larger molecules like proteins and cells. As the filtered fluid, or filtrate, travels through the tubule, useful substances are reabsorbed into the bloodstream, while waste products and excess ions are secreted into the filtrate. The end product, urine, moves from the kidneys through the ureters to the bladder, where it is stored before being excreted from the body.
What are the kidney diseases?
Kidney diseases are disorders that affect the structure and function of the kidneys.
Chronic Kidney Disease (CKD): A gradual kidney failure over time, usually caused by diabetes and high blood pressure.
Acute Kidney Injury (AKI): A sudden loss of kidney function due to an injury, illness, or certain medications.
Glomerulonephritis: Inflammation of the glomeruli, leading to damage to the kidney's blood-filtration function.
Polycystic Kidney Disease: A genetic disease that results in the formation of multiple cysts in the kidneys.
Kidney Stones: Hard mineral deposits that form inside the kidneys, causing pain and urinary problems.
Urinary Tract Infections (UTIs): Infections that can affect the kidneys if not properly treated.
Kidney Disease is typically diagnosed and treated with urine examination, blood tests, scans, and medication.
Biomarkers for Kidney Diagnostic
Serum Creatinine: A byproduct of muscle metabolism, high concentrations can reflect kidney failure.
Glomerular Filtration Rate (GFR): The measure of how much blood is passed through the glomeruli per minute. It's a crucial marker for kidney health.
Blood Urea Nitrogen (BUN): A waste product from protein metabolism, which the kidneys usually eliminate from the blood. Elevated levels may indicate kidney dysfunction.
Urinalysis: Examination of urine for substances such as proteins, glucose, or blood that can indicate kidney damage.
Albuminuria (Urine Albumin-to-Creatinine Ratio - UACR): The presence of albumin (a type of protein) in the urine can signal kidney damage.
Cystatin C: A kidney filtered protein that can be used to measure kidney function.
Electrolytes and Minerals: Levels of potassium, sodium, calcium, and phosphorus in the blood can reflect kidney function.
Imaging Tests: Though not biomarkers, tests like ultrasound or CT scans can identify structural changes in the kidneys.
These biomarkers are typically combined to measure kidney function as a whole.
How Urinalysis is used for Kidney Function Diagnostics
Assessment of Urine Appearance:
Color and Clarity: Abnormal urine color and cloudiness can indicate different types of kidney problems. For instance, red or dark brown urine could suggest the presence of blood, which may occur in kidney disease.
Chemical Analysis:
Protein Level: Proteinuria (excess protein in urine) can be an early sign of kidney damage.
Glucose: The presence of glucose can indicate diabetes, which is a leading cause of kidney dysfunction.
pH Level: Abnormal pH levels might indicate a kidney or urinary tract dysfunction.
Ketones: Ketones in urine can indicate severe diabetes or other conditions affecting kidney function.
Microscopic Examination:
Cells: The presence of white or red blood cells indicates infection or kidney inflammation.
Casts: These tube-shaped particles can be a sign of kidney disease.
Crystals: Crystals are a sign of kidney stones and this can impair kidney function.
What Are the Benefits of Urinalysis
- Early Detection: Urinalysis can identify kidney related disorders even before symptoms are present.
- Non-Invasive: It is a simple, non-invasive test that only requires a urine sample.
- Comprehensive Health Indicator: Apart from kidney function, Urinalysis can tell us more about health like infection level and metabolic disorders.
- Convenient and Quick: The results can often be obtained quickly, allowing for rapid assessment and management of conditions.
- Cost-Effective: It is generally less expensive compared to more invasive tests or imaging studies.
Case Study
Case 1: Schulz CA, Engström G, Nilsson J, Almgren P, Petkovic M, Christensson A, Nilsson PM, Melander O, Orho-Melander M. Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years. Nephrol Dial Transplant. 2020 Feb 1;35(2):265-273. doi: 10.1093/ndt/gfy382. PMID: 30629206; PMCID: PMC7049260.
Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012).
Fig2. Association between baseline p-KIM-1 and decreased longitudinal kidney function and incidence of CKD in MDCS-CC. (a) Annual change in eGFR through quartiles of fasting p-KIM-1 at baseline among 2799 participants in the MDCS-CC during a mean follow-up time of 16.6 ±1.5 years. Data are shown as mean (SE). The GLM was adjusted for age, sex and baseline eGFR.Case 2: Payasi A, Yadav MK, Chaudhary S, Aggarwal A. Evaluating nephrotoxicity reduction in a novel polymyxin B formulation: insights from a 3D kidney-on-a-chip model. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0021924. doi: 10.1128/aac.00219-24. Epub 2024 Sep 3. PMID: 39225483; PMCID: PMC11459911.
This study aimed to assess the nephrotoxicity associated with VRP-034 (novel formulation of polymyxin B [PMB]) compared to marketed PMB in a three-dimensional (3D) kidney-on-a-chip model. A suite of novel kidney injury biomarkers, cell health, and inflammatory markers were quantitatively assessed in the effluent.
Fig3. Biomarker levels after 12-, 24-, and 48-h exposures with marketed PMB and VRP-034. (A–G) Levels of KIM-1, cystatin-C, clusterin, NAG, NGAL, and osteopontin in the effluent of human RPTEC/hTERT1 cells after 12, 24, and 48 h of exposure with different concentrations of marketed PMB and VRP-034.