Glomerular Filtration

The kidneys are two reddish-brown, bean-shaped organs found in vertebrates. They are located on the left and right sides of the retroperitoneal space in adults and are about 12 centimeters long. They have paired renal arteries and veins that carry blood into and out of them. Each kidney has a ureter, a tube that carries urine from the kidneys to the bladder.

The kidney takes involved in the regulation of toxin elimination, fluid osmolality, acid-base balance, various electrolyte concentrations, and volume of various body fluids. One-fifth of the blood volume that enters the kidneys is filtered in the glomerulus, where filtering takes place. Amino acids, salt, bicarbonate, glucose, and solute-free water are a few examples of compounds that are reabsorbed. Hydrogen, ammonium, potassium, and uric acid are a few examples of chemicals that are released. The structural and operational unit of the kidney is the nephron. A mouse kidney only has about 12,500 nephrons, compared to the roughly 1 million seen in an adult human kidney. Additionally, the kidneys perform tasks that are not dependent on the nephrons. For instance, they produce the hormones erythropoietin and renin, as well as the conversion of a precursor of vitamin D into its active form, calcitriol.

Glomerular Filtration

Glomerular filtration precedes the generation of urine. It is the process through which your kidneys filter surplus fluid and waste from your blood into the kidney’s urine-collecting tubules, enabling your body to dispose of them.

Why we make urine?

Most people don’t give much thought to the process of urinating unless something goes wrong, but your kidneys and urinary system are actually very impressive. Together, they receive more than a liter of blood every minute and excrete around 1.5 liters of urine each day, effectively eliminating extra water and waste that would otherwise cause you major difficulties. 

Your body metabolizes (processes) the food and liquids you consume to create energy as well as the many building blocks required to maintain the health of your tissues and organs. As a result, numerous more compounds are created, many of which must be removed to avoid hazardous buildup because they cannot be used immediately or stored for later. In addition to waste products, our diets frequently include compounds in quantities substantially greater than what we require on a daily basis (such as carbohydrates and fats). You eliminate both water-soluble and non-water-soluble waste materials in your urine and feces, such as bacteria and undigested fiber (e.g., urea and electrolytes – sodium and potassium). Beets, blackberries, and rhubarb, for example, can turn urine red or pink. Certain foods and medications can also alter the color of your urine. This is proof that the vibrant soluble pigments are being excreted from your body through your kidneys.

Urine primarily excretes the following substances:

• Metabolic byproducts, such as urea and creatinine
• Your body employs electrolytes, which are inorganic substances such as sodium, potassium, calcium, chloride, and bicarbonate, to regulate the fluid content of your body fluids.
• Water

Working of Glomerular Filtration

The initial stage in producing urine is to separate your blood cells from your plasma, which contains all of the dissolved solutes. Your glomeruli, which are small filters found in each nephron of your kidneys, are constantly filtering your blood.

Blood that is about to be filtered enters a glomerulus, which is a group of blood capillaries (the smallest of blood vessels). The glomerulus is housed within a cup-shaped sac at the end of each nephron, known as the glomerular capsule. Similar to a sieve with an extremely fine mesh, glomerular capillaries have tiny pores in their walls. The majority of capillary beds are surrounded by venules and arterioles, which are the tiny blood arteries that transport blood to and collect blood from capillary beds. As blood passes through the capillary bed and into the venules and veins, the hydrostatic pressure decreases. Afferent arterioles provide blood to the glomerulus, whereas efferent arterioles remove it. The glomerulus, on the other hand, is positioned between two arterioles. As blood leaves the glomerulus, efferent arterioles contract, creating resistance to blood flow and avoiding a pressure decrease that would not be possible if blood were to pass into venules, which do not actually constrict. The two arterioles enlarge or contract to alter glomerular blood pressure. Efferent arterioles also have a reduced diameter compared to afferent arterioles. As a result, pressured blood is forced to escape the glomerulus through a narrower tube after entering through a relatively wide tube. Together, these special characteristics and the fact that your heart pumps over a liter of blood (or 20% of its total output) to your kidneys every minute help to maintain a high glomerular capillary pressure and the kidney’s ability to filter blood independent of changes in blood flow. The efferent arteriole, for instance, can be stimulated to constrict during exercise when the blood supply to the kidney is lowered by the sympathetic nervous system.

The glomerular capillary wall’s physical characteristics determine what is filtered and how much is filtered into the glomerular capsule. The capillary walls are composed of three layers, which are arranged from the inside out:

• Endothelium – This possesses relatively wide pores (70–100 nanometers in diameter), but blood cells cannot flow through them. Instead, solutes, plasma proteins, and fluid can.
• Basement membrane – This membrane is connected to the endothelial layer and has three layers as well. Its function is to stop the circulation from being filtered by plasma proteins.
• Epithelium – Podocytes, specialized cells, make up this layer. These cells have foot processes that anchor them to the basement membrane (pedicels). They leave filtering gaps between them as they wrap around the capillaries. Before the fluid enters the glomerular region, a narrow diaphragm in between the slits serves as a final filtration barrier.

A renal corpuscle is a collective name for the glomerulus and glomerular capsule filtering unit.

The peritubular capillaries, which are tiny blood vessels that run parallel to and surround the proximal and distal tubules of the nephron as well as the loop of Henle, where they are known as the vasa recta, are additional specialized capillaries found in the kidneys in addition to the distinct glomerular capillary bed. For countercurrent exchange, which concentrates urine, the vasa recta are crucial.

Glomerular Filtration Rate (GFR)

The glomerular filtration rate is the term used to describe how quickly the kidneys filter blood. The blood pressure that enters the glomerulus serves as the primary driving force for the filtering procedure or outward pressure. The hydrostatic pressure of the fluid in the urinary space and the pressure produced by the proteins left in the capillaries, which have the tendency to draw water back into the circulatory system, partially offset this (colloidal osmotic pressure). The difference between the internal and the outside pressures is the net filtration pressure.

How is the glomerular filtration rate regulated?

While it may come as a surprise to you, it is totally common for your blood pressure to change throughout the course of the day; nonetheless, this has no bearing on your glomerular filtration rate. This is due to the fact that your body can precisely control it in normal circumstances:

Intrinsic mechanisms

• Renal autoregulation: The afferent arterioles can be made to dilate or constrict by the kidney itself, counteracting changes in blood pressure. This intrinsic system functions properly throughout a wide range of blood pressure, but kidney illness can cause it to malfunction.

Extrinsic mechanisms

• Neural (nervous system) control and hormonal control – When necessary, these extrinsic mechanisms can suppress the glomerular filtration rate and override renal autoregulation. For instance, your nervous system will promote the afferent arteriole’s contraction if your blood pressure significantly drops, which might happen if you lose a lot of blood. This will cause you to produce less pee. Your nervous system can also activate the renin-angiotensin-aldosterone system, a hormone system that controls blood pressure and fluid balance if additional action is required.
• Hormonal control – A hormone that can raise the glomerular filtration rate is an atrial natriuretic peptide. Your heart produces this hormone, which is released when your plasma volume rises and urine production rises.

Measurement of GFR 

GFR is calculated as the clearance of exogenous filtration indicators, such as inulin, iohexol, iothalamate, technetium 99m diethylenetriamine pentaacetic acid, and chromium 51-ethylenediamine tetraacetic acid, which are exclusively removed via glomerular filtration. In order to accurately calculate the clearance curve using plasma clearance techniques, patients must stay inpatient or in the clinic for several hours. As a result, GFR measurements using these techniques remain impractical and expensive with common methodologies (e.g., iohexol or inulin by plasma clearance or nuclear renal scans), and are not frequently carried out in clinical practice or large-scale clinical research.

Consequently, endogenous filtration indicators are frequently used to determine GFR. Patients at risk of developing early renal disease when GFR is normal to raised would benefit from having their GFR evaluated using more exact and precise methods, even though estimated GFR is often sufficient for clinical decision making, especially when GFR is < 60 ml/min/1.73m². Due to the possibility of early therapies intended to stop the progression of kidney disease, the early detection of diminishing renal function may be crucial. Early intervention is one justification for the Preventing Early Renal Loss (PERL) Study, whose endpoint changes in GFR as determined by iohexol. Therefore, precise and accurate diagnostic methods used in a clinical environment are required to identify kidney disease in its early stages.

Inulin, which has been used for decades as the gold-standard measure of GFR, is one of many ways to measure GFR. To achieve the optimum outcomes, inulin must be collected through urine collection or continuously infused, both of which provide substantial challenges for its widespread use. There are a number of radioisotopes, including ⁹⁹mTc-DTPA, ⁵¹Cr-EDTA, and ¹²⁵Iothalamate, but their application outside of research investigations is difficult due to logistics, expense, and radiation exposure, especially in asymptomatic young adults and/or adolescents. The kidney does not absorb, metabolize, or produce iohexol or non-radioactive iothalamate, which are nonionic, low osmolar contrast agents. Low toxicity for iohexol has been observed in radiology practice (contrast x-rays), where dosages 10–50 times larger than those required for GFR assessment are employed. In the Prevent Early Renal Loss (PERL) project, our institutions have safely measured GFR by iohexol clearance over 1000 times without any problems. In fact, for more than 20 years, publications have asserted that the gold-standard GFR measurement is iohexol. In 2226 research participants between 2011 and 2016, the Advanced Research and Diagnostic Laboratory at the University of Minnesota effectively assessed iohexol to evaluate GFR.

Decreased GFR

A low GFR indicates that your kidneys aren’t properly filtering your blood.

You have renal disease if your GFR is less than 60. You have renal failure and will need dialysis or a kidney transplant if the number is less than 15.

Chronic Kidney Disease (CKD)

The function of your kidneys is described by the five phases of CKD. With time, kidney disease can worsen. Your kidneys are still able to filter waste out of your blood throughout the early stages (Stages 1-3). Your kidneys may stop functioning entirely and must work harder to filter your blood in the latter stages (Stages 4-5).

At every stage of CKD, you should take action to slow down kidney damage and prolong the time that your kidneys are able to function.

• Stage 1 of CKD: If your eGFR is normal or over 90, you have stage 1 CKD, which means your kidneys have just minor damage. It’s possible that you are symptom-free because your kidneys are still functioning properly. In addition to protein in your urine, you might exhibit other kidney disease symptoms.
• Stage 2 of CKD: If you have stage 2 CKD, your eGFR has decreased to between 60 and 89 and you have modest renal damage. Since your kidneys often function normally, you might not experience any symptoms. Other symptoms of kidney impairment could include bodily harm or protein in your urine.
• Stage 3 of CKD: If you have stage 3 CKD, your eGFR is between 30 and 59 and your kidney damage is modest to moderate. Your kidneys do not filter trash and extra fluid from your blood as effectively as they should. The accumulation of this waste in your body can lead to various health issues like high blood pressure and bone damage. Your hands or feet could swell, and you could start to feel weak and exhausted.
  Depending on your eGFR, stage 3 CKD is divided into two substages:
  • You are in stage 3a if your eGFR is between 45 and 59.
  • You are in stage 3b if your eGFR is between 30 and 44.

Many Stage 3 patients who receive therapy and make healthy lifestyle adjustments do not go to Stage 4 or Stage 5.

• Stage 4 of CKD: If you have stage 4 CKD, your eGFR is between 15 and 29, and your kidneys have suffered moderate to severe damage. Your kidneys’ ability to filter waste from your blood is not as good as it could be. Your body may accumulate this waste, which could lead to heart disease, high blood pressure, and other health issues like bone and heart disease. You’ll probably have symptoms including lower back ache and hand and foot swelling.  This is the last stage before kidney failure. To prevent kidney deterioration and prepare for potential therapies for kidney failure, it is crucial to schedule regular appointments with a nephrologist (kidney specialist).
• Stage 5 of CKD: If you have stage 5 CKD, your eGFR is less than 15 and your kidneys have suffered significant damage. Your kidneys are either already failing or are very near to failing (stopped working). Waste products accumulate in your body as a result of your kidneys’ inability to filter waste from your blood, which can make you very ill and result in various health issues. Dialysis or a kidney transplant are two possibilities for treatment when your kidneys fail.

FAQs on Glomerular Filtration Rate

Question 1: What is the filtration membrane, how does it work, and what materials does it consist of?

Answer:

A filter is a  barrier between the blood and the glomerular capsule’s interior.

Consists of 3 layers:

1. Endothelium with fenestration.
2. The capsule of the glomerulus’ visceral membrane.
3. The basement membrane, which is made up of the basal laminae of the other two layers fused together.

Question 2: What is a glomerular filtration rate (GFR) test?

Answer:

A blood test called a glomerular filtration rate (GFR) measures how well your kidneys are functioning. Glomeruli are little filters found in your kidneys. These filters aid in clearing the blood of waste and extra fluid. How much blood flows through these filters each minute is determined by a GFR test.

A GFR can be directly assessed, however, it is a challenging procedure that needs skilled experts. As a result, the most common method for estimating GFR is the estimated GFR test or eGFR. Your provider will employ a technique called a GFR calculator to obtain an estimate. A formula that calculates the rate of filtration is known as a GFR calculator.

Question 3: What is the use of the GFR test?

Answer:

When kidney illness is most easily treated, an early diagnosis is made with the aid of a GFR test. A person with chronic kidney disease (CKD) or another disorder that damages the kidneys may also be monitored using GFR. These include hypertension and diabetes.

Question 4: What is impermeable to the glomerular filter?

Answer:

Due to the effects of the glomerular capillary filtration membrane’s size barrier and charge barrier, heavy molecular weight proteins in the plasma (such as albumin and globulin) cannot normally pass through the filtration membrane.

Question 5: What kind of filtration does the glomerulus employ?

Answer:

Renal ultrafiltration is the method by which glomerular filtration takes place. The filtrate is pushed out of the capillaries and into the slits in the nephron by the force of hydrostatic pressure in the glomerulus, which is the force of pressure produced from the pressure of the blood artery itself.

Question 6: What is necessary for glomerular filtration?

Answer:

Glomerular filtration is dependent on the same opposing forces—hydrostatic pressure and oncotic pressure, together known as Starling’s forces—that cause the fluid exchange in every capillary in our body.