How Do the Kidneys Filter Blood? — A Sieve That Takes Almost Everything Back

The 160 Grams That Do Not Appear in Your Urine

A healthy person's kidneys filter about 160 grams of glucose a day. This is an amount equivalent to roughly 30 percent of the calories consumed in a day. Yet this glucose is not discarded in the urine, but is instead reabsorbed back into the blood inside the kidneys (PMID 27878313). There is a reason why an organ that filters blood pulls back what it has filtered, and this article follows that reason.

The kidneys are a pair of bean-shaped organs located in the upper back on either side of the waist, which filter the blood to send out waste products and excess water as urine. In Korean, they are also called sinjang.

If you picture a kitchen sieve, you can see the way the kidneys filter. When you pour boiled noodles into a sieve, the water drains out and only the noodles remain. The kidney's sieve works in reverse. It lets water and small substances pass broadly out of the blood, and then fishes almost all of the necessary substances back up from what fell through. What is left behind without being fished back up becomes urine.

Yet a kitchen sieve just sits still. The kidneys use energy to fish things back up (PMID 39025993), and they adapt to the body's condition from moment to moment, such as by adjusting the amount they excrete when the amount of potassium eaten changes (PMID 27756725). It is a sieve that decides every day what and how much to retrieve.

The sequence is as follows. We will first look at the path urine takes and the smallest unit that filters the blood, and see how the work of filtering and reclaiming balances water, salt, and blood pressure. Passing through the signals that go to red blood cells and bones, and the function that diminishes with age, we will arrive at why the breakdown of the kidneys leaves traces across many parts of the body.

From Kidney to Outside the Body — The Urinary Tract

Urine is made in the kidneys, but it collects and leaves from the lower abdomen. Tubes and a pouch connect the two.

The ureter is a thin tube that sends urine made in the kidney to the bladder. One comes down from each kidney, left and right.

The bladder is a muscular pouch that stores urine and lets it out. Even though urine is made without stopping in the kidneys, we only go to the bathroom a few times a day thanks to this pouch.

The urethra is the final tube through which urine from the bladder goes outside the body. From the kidneys, past the ureter and bladder, and all the way to the urethra, this entire path that urine travels is called the urinary tract in this article.

Kidney stones where stones get stuck in this path, urinary tract infections where bacteria crawl back up, and bladder and urethral urine problems are followed one by one by other parts of this series. This article goes inside the kidneys, the starting point of the path.

The Nephron — A Single Tangle of Thread and a Thin Tube

Inside the kidney, there are many tiny devices that filter the blood. The nephron is the smallest unit of the kidney that filters blood to make urine, consisting of a filtering part and a thin tube through which the filtered water passes. The total amount filtered by the entire kidney is the sum of the amounts filtered by each individual nephron (PMID 35365815).

The glomerulus is a tangle of fine blood vessels at the very front of the nephron that filters water and small substances from the blood. Blood passes through the walls of the glomerulus and is filtered, and the filtered water collects in a small pouch surrounding the glomerulus (PMID 35365815). Blood cells and large proteins cannot pass through this wall and remain inside the blood vessel.

The tubule is a thin tube through which the water filtered in the glomerulus passes, returning what the body needs back to the blood and adding what is left over to make urine. Compared to a sieve, the glomerulus is the side that lets everything pass broadly, while the tubule is the side that scoops things back up.

How hard the kidney works is measured by the amount it filters. The glomerular filtration rate is the amount of water in the blood filtered by the kidney's glomeruli per minute, representing the primary number that indicates how well the kidney is working. It is a value obtained by dividing the filtered amount by time, and the value for the entire kidney is the sum of the values from each nephron (PMID 35365815). Therefore, if the number of working nephrons decreases, even if the remaining nephrons each filter more, the overall number for the kidney may stay within the normal range or fall below it (PMID 35365815).

The numbers you see on a health checkup report are usually estimates of this. Creatinine is a waste product produced mainly by muscles, and because the kidney filters and excretes it, its concentration in the blood is used to gauge kidney function. eGFR is an estimated value of the glomerular filtration rate obtained by plugging information such as age and sex into a formula along with the blood creatinine concentration. Which formula is used to make the estimate, and what those numbers cannot tell you, is followed up in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through".

Because the amount filtered by the kidney is the sum of the amounts filtered by each individual nephron, the number of working nephrons drives that number.

Filtering, Reclaiming, and Sending Out

The plasma—that is, the liquid portion of the blood—filtered by both kidneys in a single day reaches 180 liters (PMID 21170887). This filtered water still contains a large amount of substances that the body cannot afford to discard, such as salt components and glucose. Reabsorption is the process by which the tubules take back what the body needs from the filtered water and return it to the blood. Taking just chlorine, which makes up salt, the kidneys must reclaim most of the filtered amount to maintain the body's balance (PMID 23798296).

Glucose can be followed with numbers. Because the tubules have the capacity to reclaim up to about 450 grams of glucose per day, they gather back without leaving any behind the roughly 160 grams that are filtered out in normal times (PMID 27878313). Reclaiming is not free. The kidneys are organs that consume a great deal of energy to perform the work of reclaiming and sending out carried out by the tubules (PMID 39025993).

The tubules also do work in the opposite direction. This is the work of sending more of what remained in the blood out into the inside of the tubes (PMID 39025993). After reclaiming what is useful from the filtered water and adding what is to be discarded, what remains becomes urine and flows into the ureter.

Now let us follow the case where the sieve overflows. When glucose in the blood becomes very high and exceeds the limit of about 450 grams per day for the filtered amount, the overflowing portion cannot be reclaimed and comes out in the urine. As long as the glomeruli continue to filter it out, this acts as a safety valve that prevents blood sugar from soaring to extremes (PMID 27878313). The condition where blood sugar remains high for a long time can be seen in What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read.

There are also drugs that intentionally reduce this reclamation. SGLT2 inhibitors, a class of diabetes drugs that block the transport pathways that reclaim glucose, lower that limit to about 80 grams a day, lowering blood sugar by sending excess glucose out in the urine. A 2017 review noted that this class is approved as a drug to lower blood sugar in people with type 2 diabetes and preserved kidney function (PMID 27878313).

This class is also intertwined with the kidneys themselves. Chronic kidney disease is a condition where the kidneys are damaged or kidney function has declined, lasting for three months or longer. The same review also introduces trial results showing that a drug of this class slows the progression of chronic kidney disease in a high-risk group with type 2 diabetes (PMID 27878313). The story of how this class is used to protect the kidneys is followed in "What Is Chronic Kidney Disease? — Lamps Going Out One by One, and the Load on Those Still Lit".

After broadly filtering water and small substances from the blood, the kidneys reclaim almost everything the body needs and send out only what remains as urine.

Water and Electrolytes — Matching Intake to Output

The amount of potassium consumed through food in a single day is roughly equal to the total amount of potassium dissolved in all the water outside our cells in the body (PMID 35727363). This means that if what comes in at once is simply left as it is, the level of potassium in the blood fluctuates greatly.

Electrolytes are components like sodium, potassium, and chloride that dissolve in the body's water and carry an electrical charge, and they are used to make nerves and muscles work. Potassium is one of the components with a particularly narrow range. Because the difference in potassium between the inside and outside of cells governs nerve signals and muscle contraction, potassium outside cells must stay within a narrow range (PMID 35727363).

The body divides this job into two stages. Potassium that has been eaten is first moved inside cells such as muscles to prevent the concentration in the blood from spiking, and for the total amount of potassium in the body, the kidneys change the amount they excrete to match the amount consumed (PMID 27756725; PMID 35727363). In an analysis pooling trials that increased potassium intake, the blood pressure of adults with high blood pressure went down (the effect was not seen in people without high blood pressure), and no adverse effects on adult kidney function were seen. The authors wrote that this result may be beneficial for most people who have no trouble with their kidneys handling potassium (PMID 23558164). Why this condition is attached is revisited in the final section.

Water is also sent out as much as it comes in. Antidiuretic hormone is a hormone released from the brain that tells the kidneys, "Keep water in the body." When the brain senses that the blood has become more concentrated, this hormone is released, and the end of the renal tubule that receives this signal reclaims more water. Thirst is the next line of defense (PMID 39435642). There are several types of channels through which water passes in the kidneys, and these are used to balance the body's water and the concentration of urine (PMID 31682170).

In studies comparing people who usually drink about 1 to 2 L less water a day with those who drink more, the blood test values of the two groups were similar, and both were within the normal range for healthy adults. What was different was the urine. The group drinking less had a smaller volume of urine that was more concentrated, and antidiuretic hormone in the blood was also higher (PMID 32210168). Both groups maintained the balance of water and electrolytes in the body, and what absorbed that difference was the urine. Based on these studies, the authors of the same review proposed a theory that the habit of drinking less and high antidiuretic hormone may be involved in the onset and progression of chronic diseases such as kidney disease, high blood pressure, and diabetes (PMID 32210168). Because this is a theory put forward by a narrative review, the weight of the evidence differs from the preceding observation that blood test values were the same. The relationship between water and kidney stones is followed by "What Is a Kidney Stone? — A Grain of Sand Caught in the Waterway".

This balancing act does not run individually piece by piece. The work of the kidneys transporting chloride is interlocked with transporting sodium, potassium, hydrogen ions (acid), calcium, and water, so adjusting one makes the others move together, and thanks to that, very precise regulation is possible (PMID 23798296).

The balance of acid and base works in the same way. Bicarbonate, a representative substance that absorbs the tilting of blood toward acidity, is also filtered together at the glomerulus, and the renal tubule reclaims most of it while sending hydrogen ions (acid) into the tubule lumen, creating new bicarbonate with that acid and returning it to the blood. A large share of the work of balancing acid and base in the blood lies in the renal tubule in this way (PMID 21170887). How the blood tips toward acid or base, and how to read those results, is traced in "The Balance of Acid and Base — Two Hands on a Seesaw, the Quick Lungs and the Slow Kidneys".

Even when the amounts eaten and drunk vary from day to day, the kidneys keep the water and electrolytes in the blood within a narrow range, and the urine absorbs the difference.

The Kidneys That Move Blood Pressure — A Chain Reaction Starting With Renin

There is a type of high blood pressure where the artery leading to the kidneys narrows or becomes blocked, reducing the blood reaching the kidneys and raising blood pressure. Called renovascular hypertension, it is a form of high blood pressure caused by an underlying factor and is often correctable (PMID 37455034). This condition reveals the kidneys' everyday job. When the kidneys notice that pressure has dropped, they send a signal that raises blood pressure (PMID 37455034).

Renin is an enzyme released into the blood by cells in the wall of the blood vessel entering the glomerulus, opening the first step of a chain reaction that guards blood pressure and salt. The site where renin comes out is right before the thin blood vessel leading to the glomerulus splits into a tangle of threads (PMID 17928544). Renin cuts a protein that the liver has made and floated into the blood, and the cut piece is trimmed one more time to reach the end of the chain (PMID 37455034). Angiotensin II is a substance made at the end of the chain started by renin, which tightens blood vessels and makes the kidneys hold onto salt and water.

One more hormone attaches to this chain. The adrenal glands are small samples perched on top of the kidneys, and their outer layer is called the adrenal cortex. Aldosterone is a hormone that comes out of the adrenal cortex and tells the kidneys, "Keep salt and water in the body." Angiotensin II tightens the thin arteries, makes the tubules reclaim more salt and water, causes aldosterone and antidiuretic hormone to be released, and also triggers thirst. These all converge on increasing the amount of blood inside the blood vessels and narrowing the vessels to raise blood pressure (PMID 37455034).

There is also a loop that goes backward. If blood pressure is high or the amounts of salt and blood are ample, less renin comes out (PMID 17928544). Eating salty food reduces the activity of renin in the blood, and eating less salt increases it, creating a feedback loop between the body's amount of salt and renin (PMID 25502115). However, the exact pathways by which salty food transmits the signal to reduce renin are still only incompletely understood, with several candidates nominated, such as the salt concentration in the tubules, blood pressure, hormones coming from the heart, and kidney nerves (PMID 25502115). The structure where a hormone receives a reply like "stop sending it" and stops is covered in "How Hormones Work — Letters Only the Addressee Reads, Replies That Say Stop".

The kidneys also sit at the center of holding blood pressure in place for a long time. When blood pressure rises, the kidneys send out more salt and water to return blood pressure back to normal, but in long-lasting high blood pressure, this response is misaligned in some form (PMID 23720252). High blood pressure is a state where high blood pressure continues, and guidelines draw the line on what value counts as high. The kidneys are involved in both how high blood pressure starts and how it continues (PMID 16810471). What the two numbers of blood pressure measure can be seen in "What Blood Pressure Measures — Two Numbers, and an Answer That Changes With Where You Measure".

Not everyone's blood pressure responds to salt with the same magnitude. Roughly 50 to 60 percent of people with high blood pressure are estimated to be on the salt-sensitive side (PMID 27757935). This sensitivity grows as people age even without kidney disease, and the reason is cited as the joint decline of the kidneys' ability to handle salt and kidney function (PMID 38545804). In analyses gathering trials that reduced salt intake, blood pressure dropped quite a bit, with the magnitude larger in people with high blood pressure and smaller in people with normal blood pressure (PMID 27757935).

Drugs that block this chain are also widely used. Renin-angiotensin system blockers are a class of blood pressure medications that block the hormone chain that raises blood pressure and traps salt in the body. They are used for treating high blood pressure, heart failure, and kidneys damaged by diabetes (PMID 19948673).

When pressure drops, the kidneys release renin to raise blood pressure; when blood pressure rises, they send out more salt and water to return it; and in long-lasting high blood pressure, this regulation is misaligned.

After a Salty Meal

Let us bring the facts we have seen together into a single scene. This is a day when you ate a salty stew for dinner and drank very little water. The first chain of events below depicts someone who is not sensitive to salt, and not everyone's kidneys move this way.

When a lot of salt enters, the activity of renin in the blood decreases, loosening the chain reaction that holds onto salt (PMID 25502115). The sieve turns its handle toward scooping up less salt.

The salt that has entered also raises the concentration of water in the blood. The brain's sensor detects this and releases antidiuretic hormone, and the end of the tubule reclaims more water (PMID 39435642). Because the kidney's water channels are used to adjust the concentration of urine (PMID 31682170), water is kept in the body and the urine becomes concentrated. If you are still thirsty, that means the next line of defense has moved (PMID 39435642).

Blood pressure moves differently for each person. When they eat more salt, some people's blood pressure rises noticeably, while for others it hardly changes. Part of this difference comes from genetic differences in the pathways that handle and excrete salt (PMID 33486988). In people sensitive to salt, after eating salty food, the renin chain reaction is instead misaligned, or the flow of blood to the kidneys increases less, leaving salt in the body (PMID 38545804). Even for the exact same bowl of stew, the way the kidneys handle salt differs from person to person.

Along with the pathways connecting salt and renin that we saw earlier, there are still unresolved parts to this picture. Textbooks teach that when you eat more salt, the salt in your body increases until the amount excreted matches the amount eaten, and then it stops there. However, when one research team fixed salt intake into three stages over several weeks and collected all the urine, the amount of salt in the body rose and fell in cycles lasting over a month, regardless of the amount eaten (PMID 24107854). This is a result measured precisely by a research team. The authors report that this finding matches ideas developed in animal studies, and they are trying to verify further in humans where and how the body stores salt (PMID 24107854).

The Signal to Make Blood, Vitamin D for the Bones

Anemia commonly follows people whose kidneys have been damaged for a long time. Anemia is a state where red blood cells are lacking in the blood, failing to sufficiently carry oxygen to every corner of the body. The main cause of anemia in someone whose kidney function has declined for a long time lies in a shortage of a single hormone made by the kidneys (PMID 7950169).

Erythropoietin is a hormone made mainly in the kidneys that tells the bone marrow to make more red blood cells. When oxygen is scarce, the amount of this hormone produced increases greatly (PMID 7950169). This is a loop that makes more red blood cells as a signal when the blood carries less oxygen.

Erythropoietin made through genetic engineering was approved as a treatment for anemia caused by kidney problems (PMID 7950169). This is what is contained in a 1994 review article. A 2013 review article evaluated that this treatment left a major impact on anemia management, noting that the concerns revealed alongside it became a strong motivation to find safer and more effective treatments (PMID 23457296).

There is also the matter of what goes toward the bones. Vitamin D made in sun-exposed skin or taken in through food cannot work as it is, and must be modified once in the liver and once again in the kidneys (PMID 20136904; PMID 38892599). Active vitamin D is the final, actually working form of the vitamin D obtained from sunlight and food, after passing through the liver and being transformed in the kidneys. Active vitamin D, which travels through the blood to the whole body, is made in the kidneys in this way.

Active vitamin D, together with other hormones, regulates the tasks of absorbing calcium in the gut, reclaiming calcium in the kidneys, and filling the bones with minerals, keeping blood calcium within a narrow range (PMID 38892599). Calcium enters solely through food, and its amount is regulated by three paths: the inflow and outflow of bones, absorption in the gut, and reclamation by the kidneys (PMID 34774235). Phosphorus, another material that hardens bones, has its concentration in the blood determined by the amount the kidneys excrete (PMID 37660247).

Beyond filtering blood, the kidneys send signals to the bone marrow to make red blood cells and transform vitamin D into its working form to support the bones.

What Shrinks with Age

Even in healthy people who underwent rigorous testing to donate a kidney, the glomerular filtration rate adjusted for body size decreased by 6.3 every 10 years (PMID 26709059). This is the number of milliliters filtered per minute, adjusted for a standard physique. This means the rate decreases with age even without disease.

You can understand why through the addition we saw earlier. The number of nephrons is fully set before birth and does not increase thereafter, remaining as they are until lost to age or disease (PMID 36646887). As people age, the number of working nephrons decreases, and the glomerular filtration rate of the entire kidney decreases roughly alongside it (PMID 34343996). In healthy older adults, the amount filtered by each remaining nephron is relatively unchanged (PMID 28790143). Every single mesh of the sieve works properly, but the number of meshes decreases.

The appearance changes as well. The volume of the outer layer of the kidney decreases, and the number and size of simple cysts increase with age (PMID 28790143). Quite a few people are told during health checkup ultrasounds that cysts were seen in their kidneys, and a doctor who looks at the images determines what kind of cysts they are.

Age itself does not damage the kidneys. However, age-related changes reduce the kidney's ability to recover from injury, tipping the balance toward vulnerability to both sudden and long-lasting kidney disease, and high blood pressure, diabetes, or pre-existing kidney disease amplify these changes (PMID 32835891). As people age, their ability to concentrate urine and retain salt decreases, and they feel less thirsty (PMID 24729151). The relationship between waking up at night due to urine and this change is explored in "Where Do Urinary Problems Come From? — A Narrowed Passage, an Alarm That Rings Too Early, a Tired Gatekeeper".

There is debate over what to call this decrease. It is a question of whether it falls under the chronic kidney disease we saw earlier. The studies reviewed in this review article counted an eGFR below 60 as chronic kidney disease based on current criteria (PMID 28790143). What those criteria look at alongside numbers is explored in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through". Albuminuria is when albumin, a protein that should not be filtered out, leaks into the urine in amounts greater than normal. In people without albuminuria, an eGFR drop below 60 with age was very slightly or almost not at all associated with the risk of death compared to people of the same age, or with the risk of end-stage kidney disease requiring dialysis or transplantation. Citing this, a 2017 review article questioned whether it is correct to give a disease name to the age-related decrease, and wrote that many older adults who fall under chronic kidney disease by current standards need a different management approach (PMID 28790143).

There is also evidence from the other side. While noting concerns that older adults are being misdiagnosed with chronic kidney disease, a 2016 review article concludes that age-related changes remain clinically meaningful. When older adults actually develop chronic kidney disease, they have less reserve function to lean on, and the risk of acute kidney injury is higher (PMID 26709059). Being older is also associated with chronic kidney disease being more common and progressing faster (PMID 34343996).

How to read a single number alongside age is explored in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through", and the definition and stages of chronic kidney disease are explored in "What Is Chronic Kidney Disease? — Lamps Going Out One by One, and the Load on Those Still Lit".

As people age, the glomerular filtration rate decreases along with the number of nephrons, and while whether to call that decrease a disease is under debate, older adults have less reserve to lean on when kidney disease develops and a higher risk of acute kidney injury.

The Traces Left When Kidneys Fail

When a person who produces almost no urine receives dialysis, they must rely on the dialysis machine to balance the salt and water in their body (PMID 28066913). The machine takes over the daily weighing and balancing that the kidneys used to do.

Each of the tasks we looked at earlier leaves a trace when the kidneys break down. When someone whose kidneys have suddenly suffered severe damage receives treatment to filter their blood with a machine, the balance of electrolytes, acid and base, and water can be brought back to normal until the kidneys recover (PMID 32854844). That means keeping that balance was the job of the kidneys. The future of someone whose kidneys have failed enough to need this kind of treatment is explored in "What Is Acute Kidney Injury? — A Tap That Suddenly Runs Dry, and Three Places to Look". When the kidneys fail to make enough erythropoietin, anemia sets in (PMID 7950169). Because the kidneys sit at the center of blood pressure control, changes in the kidneys such as a dwindling number of glomeruli and nephrons become intertwined with high blood pressure (PMID 16810471).

Potassium leaves its trace as well. Potassium staying high in the blood for a long time commonly comes from the kidneys losing their ability to flush potassium out, as seen in chronic kidney disease or with certain medications—and the renin-angiotensin system blockers we looked at earlier belong to those drugs (PMID 31800077). High potassium can lead to life-threatening complications like cardiac arrest (PMID 31800077). Because this family of drugs is widely used for kidneys damaged by high blood pressure, heart failure, and diabetes (PMID 19948673), deciding how to care for someone at risk of rising potassium involves a delicate balancing act (PMID 31800077). This is why the potassium study we saw earlier came with the condition "provided there is no problem with how the kidneys handle potassium." What and how much someone with kidney disease or someone taking these drugs should eat, how the medications should be used, and how potassium should be monitored are decided by a doctor who knows that person's test results and medical condition.

These traces are picked up one by one by other parts of this series. The numbers that measure how hard the kidneys are working are covered in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through", the disease where function slowly declines is covered in "What Is Chronic Kidney Disease? — Lamps Going Out One by One, and the Load on Those Still Lit", and sudden collapse over a few days is covered in "What Is Acute Kidney Injury? — A Tap That Suddenly Runs Dry, and Three Places to Look". The paths where a machine or another person's kidney takes over the work and the path where they do not are covered in "Dialysis and Kidney Transplantation — Three Sieves That Stand In, and the Path That Uses None", while stones, infections, and urinary problems that arise in the urinary tract are handled in their respective installments.

Because the kidneys handle water, electrolytes, blood pressure, and red blood cells alongside filtration, when the kidneys break down, their traces are left all over the body.

Where Else to Look

The two blood pressure numbers that the kidneys affect can be further explored in "What Blood Pressure Measures — Two Numbers, and an Answer That Changes With Where You Measure", and the general principles of hormones that renin, aldosterone, and antidiuretic hormone follow are in "How Hormones Work — Letters Only the Addressee Reads, Replies That Say Stop". High blood sugar, the baseline where glucose overflows into the urine, is covered by "What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read", the liver that supplies materials to the renin cascade by "What Does the Liver Do, and What Do Liver Tests Measure? — The Factory at the Gate, and the Signal That Leaks Through the Wall", and the heart that pumps blood to the kidneys by "How the Heart Moves Blood — Four Chambers, Four Doors, Two Loops".

Two questions also remain unanswered. Where and how the body stores and expels salt, and from what point on reduced kidney function with age should be called a disease.

Source Papers

• "Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition." (2017) — PMID 27878313 — A healthy kidney filters about 160g of glucose a day (roughly 30% of caloric intake) and reabsorbs up to roughly 450g, letting any excess spill into the urine as a safety valve. When SGLT2 is inhibited, this limit drops to about 80g, and it is approved as a blood-sugar-lowering agent for people with type 2 diabetes and maintained kidney function.
• "Pathological mechanisms of kidney disease in ageing." (2024) — PMID 39025993 — The kidney is a metabolically active organ that spends energy on tubular reabsorption and secretion, and its function declines with age.
• "Physiology and pathophysiology of potassium homeostasis." (2016) — PMID 27756725 — The kidney alters potassium excretion to match changes in intake, keeping total body potassium balanced, while insulin and beta-adrenoreceptors handle distribution inside and outside cells.
• "Glomerular hyperfiltration." (2022) — PMID 35365815 — Blood passes through the glomerular barrier to form filtrate in Bowman's space. GFR is the filtration volume per hour, total GFR is the sum of each nephron's GFR, and when the number of nephrons drops, GFR can remain normal or low even with hyperfiltration in the remaining individual nephrons.
• "Chloride transport." (2012) — PMID 23798296 — The kidney must reabsorb most of the filtered chloride, and chloride transport is intertwined with sodium, potassium, protons, calcium, and water to allow precise regulation.
• "Potassium homeostasis: sensors, mediators, and targets." (2022) — PMID 35727363 — Daily potassium intake rivals the potassium of the entire extracellular fluid, and because the potassium gradient dictates membrane potential and muscle contraction, it is held within a tight range, regulated by internal-external cellular distribution and renal excretion, with potassium influencing aldosterone production.
• "Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses." (2013) — PMID 23558164 — Increased potassium intake lowered blood pressure in adults with hypertension without harming kidney function, and can be beneficial for most people whose kidneys handle potassium normally.
• "The biology of water homeostasis." (2025) — PMID 39435642 — Water balance is maintained through the brain's osmosensors triggering antidiuretic hormone, which opens water channels in the collecting ducts to reabsorb water, with thirst acting as the second line of defense.
• "Aquaporins in the kidney: physiology and pathophysiology." (2020) — PMID 31682170 — The kidney is the central organ for water and sodium balance, and nine types of human renal aquaporins are crucial for body water balance and urine concentration.
• "Distinguishing Low and High Water Consumers-A Paradigm of Disease Risk." (2020) — PMID 32210168 — Low and high water consumers differ by 1 to 2L a day, with similar blood values that fall within the normal range, but differing urine volume, concentration, and antidiuretic hormones; the authors propose a theory that low consumption increases disease risk (narrative review).
• "Nonatherosclerotic Renovascular Hypertension." (2023) — PMID 37455034 — When renal blood flow drops, the pressure drop triggers renin release, converting hepatic angiotensinogen into angiotensin I and then II, raising blood pressure through vasoconstriction, tubular sodium and water reabsorption, aldosterone, antidiuretic hormone, thirst, and sympathetic nerve activity.
• "Renin release." (2007) — PMID 17928544 — Renin is secreted by wall cells of the afferent arteriole at the entrance of the glomerular capillary network, stimulated by sympathetic nerves and prostaglandins, and suppressed by angiotensin II, high blood pressure, salt, and volume overload.
• "Salt feedback on the renin-angiotensin-aldosterone system." (2015) — PMID 25502115 — A salt load or high-salt diet suppresses plasma renin activity while salt restriction stimulates it, forming a salt-renin feedback loop whose signaling pathways are still incompletely understood (four candidate regulators).
• "Hypertension: physiology and pathophysiology." (2012) — PMID 23720252 — The kidney is central to long-term blood pressure control, and the pressure-natriuresis response is abnormal in all chronic hypertension.
• "[Kidney and hypertension]." (2006) — PMID 16810471 — The kidney is involved in the initiation and maintenance of hypertension, and structural changes such as a reduced number of glomeruli and nephrons are one of the mechanisms.
• "Impact of Salt Intake on the Pathogenesis and Treatment of Hypertension." (2017) — PMID 27757935 — An estimated 50 to 60% of hypertension patients are salt-sensitive, and reducing salt lowers blood pressure, with a larger drop in the hypertensive group and a smaller one in the normotensive group (meta-analyses).
• "Salt-Sensitive Hypertension and the Kidney." (2024) — PMID 38545804 — Salt sensitivity increases with age, and impaired renal sodium handling and function are cited as causes even without kidney disease.
• "The renal renin-angiotensin system." (2009) — PMID 19948673 — RAS inhibition is widely used to treat hypertension, heart failure, and diabetic kidney disease.
• "Epithelial Sodium Channel and Salt-Sensitive Hypertension." (2021) — PMID 33486988 — There is a spectrum where some people experience a large rise in blood pressure with salt intake while others experience almost no change.
• "Spooky sodium balance." (2014) — PMID 24107854 — In an experiment where salt intake was fixed across three multi-week stages and all urine was collected, total body sodium fluctuated in cycles of over a month regardless of intake (one research team).
• "Biology of erythropoietin." (1994) — PMID 7950169 — Erythropoietin is a survival and growth factor for bone marrow red blood cell precursors, made primarily in the kidney and greatly increased by hypoxia, and its deficiency is the main cause of chronic renal failure anemia, with recombinant erythropoietin approved as a treatment for renal anemia.
• "Erythropoietin." (2013) — PMID 23457296 — Erythropoietin treatment left a major impact on anemia therapy, and the concerns that emerged alongside it motivated the development of safer treatments.
• "Vitamin D metabolism." (2010) — PMID 20136904 — Vitamin D3 made in the skin becomes the active form (calcitriol) through two successive hydroxylations in the liver and kidney.
• "Physiology of Vitamin D-Focusing on Disease Prevention." (2024) — PMID 38892599 — Vitamin D becomes 25(OH)D in the liver and calcitriol in the kidney, which, together with parathyroid hormone, regulates blood calcium through intestinal absorption, renal reabsorption, and bone mineralization (only the physiological description from this paper is cited).
• "Physiology of Calcium Homeostasis: An Overview." (2021) — PMID 34774235 — Calcium enters only through food and is regulated by hormones via bone turnover, intestinal absorption, and renal reabsorption.
• "The basics of phosphate metabolism." (2024) — PMID 37660247 — Phosphorus is essential for bone stability, and renal excretion determines whole-body phosphorus concentrations.
• "Structural and Functional Changes With the Aging Kidney." (2016) — PMID 26709059 — In healthy donors, GFR decreases by 6.3 mL/min/1.73㎡ per decade; while there is a risk that older adults might be misdiagnosed with CKD, it holds clinical significance because they have less functional reserve and a higher risk of acute kidney injury.
• "Structural and Functional Changes in Human Kidneys with Healthy Aging." (2017) — PMID 28790143 — With age, cortical volume decreases and simple cysts increase; overall GFR drops with the loss of nephrons while GFR per nephron remains relatively constant; age-related eGFR <60 without albuminuria raises the risk of death and end-stage kidney disease very little or not at all, raising the question of whether a disease label is appropriate.
• "Aging-Related Kidney Diseases." (2021) — PMID 34343996 — Older age is linked to increased prevalence and progression of CKD, with the loss of nephrons roughly paralleling the drop in GFR.
• "The ageing kidney: Molecular mechanisms and clinical implications." (2020) — PMID 32835891 — Aging itself does not cause kidney damage, but it diminishes resilience, making the kidneys vulnerable to acute and chronic kidney disease, while hypertension, diabetes, and pre-existing kidney disease amplify these changes.
• "Renal physiology of nocturia." (2014) — PMID 24729151 — As people age, urine-concentrating and sodium-conserving abilities decline, and the sensation of thirst also decreases.
• "Dialysate Sodium: Rationale for Evolution over Time." (2017) — PMID 28066913 — Hemodialysis patients who produce almost no urine rely on the dialysis machine for sodium and water balance.
• "Contemporary Management of Severe Acute Kidney Injury and Refractory Cardiorenal Syndrome: JACC Council Perspectives." (2020) — PMID 32854844 — Acute renal replacement therapy can restore electrolyte, acid-base, and fluid balance to normal until the kidneys recover.
• "Hyperkalemia and blood pressure regulation." (2019) — PMID 31800077 — Chronic hyperkalemia is often linked to impaired renal potassium excretion (such as from chronic kidney disease or certain medications like RAAS inhibitors) and can involve life-threatening complications like cardiac arrest.
• "Acid-base transport by the renal proximal tubule." (2010) — PMID 21170887 — The kidney filters 180L of plasma a day, and the proximal tubule reclaims most of the filtered bicarbonate coupled with hydrogen ion secretion while generating new bicarbonate, primarily governing plasma bicarbonate.
• "The impact of intrauterine growth restriction and prematurity on nephron endowment." (2023) — PMID 36646887 — The nephron count of a full-term infant reaches its maximum around 36 weeks of gestation, does not increase thereafter, and is maintained until lost through aging or disease.