The Kidneys as Chemical Filters

Every day your kidneys filter about 180 litres of fluid out of your blood — the entire plasma volume roughly 60 times over — and then put almost all of it back. Only about 1.5 litres leaves as urine. It sounds wasteful, but it’s a clever chemical strategy: throw nearly everything out, then selectively reclaim what’s valuable. Along the way the kidneys control water, salt, pH and blood pressure. This article explains that strategy with the chemistry that makes it work.

The nephron: a chemical processing line

Each kidney contains around a million nephrons, tiny tubes that each do the whole job in miniature. A nephron has four main stages:

1. Glomerulus and Bowman’s capsule — filtration.
2. Proximal convoluted tubule — bulk reabsorption.
3. Loop of Henle — creating a salt gradient to concentrate urine.
4. Distal tubule and collecting duct — fine-tuning under hormone control.

Step 1: filtration by size and charge

Blood arrives at the glomerulus, a knot of leaky capillaries, at relatively high pressure. Water and small dissolved particles are pushed through a three-layer filter into Bowman’s capsule. The filter sorts molecules by:

• Size: small molecules and ions (water, glucose, amino acids, urea, Na⁺, K⁺, Cl⁻) pass freely. Large proteins and blood cells stay in the blood.
• Charge: the filter carries negative charges, which repel negatively charged proteins. Albumin, the main plasma protein, is just about small enough to squeeze through by size, but its negative charge keeps it back.

This is why protein in urine is an early warning sign of kidney damage: the filter has lost its selectivity. The fluid that passes through, called the filtrate, is essentially plasma without the proteins.

The rate at which blood is filtered is the glomerular filtration rate (GFR), about 125 cm³ per minute in a healthy adult. Blood tests estimate it from creatinine (see blood chemistry).

Step 2: taking back the good stuff

The filtrate contains glucose, amino acids, vitamins and most of the body’s salt. Losing these would be disastrous, so the proximal tubule reclaims them:

• Glucose is reabsorbed by transporters that carry it together with sodium (SGLT2 and SGLT1). In a healthy person, virtually all filtered glucose is reclaimed.
• Amino acids are taken back by their own sodium-linked carriers.
• About two-thirds of the sodium and water are reabsorbed here.
• Hydrogencarbonate is reclaimed to keep the blood’s buffer stocked.

The driving force for much of this is the sodium–potassium pump on the blood side of the tubule cells, which keeps sodium low inside them. Sodium then flows into the cells from the filtrate, and other substances “hitch a ride” (see electrolytes in the body). Water follows by osmosis.

The transporters have a limit. When blood glucose is very high — above about 10 mmol dm⁻³ — the carriers are saturated and glucose spills into the urine. That’s why sweet-tasting urine was a diagnostic sign of diabetes for centuries. Some modern diabetes drugs (SGLT2 inhibitors) deliberately block the glucose transporter, so excess glucose is excreted in urine.

Step 3: the loop of Henle and concentrated urine

Humans can produce urine much more concentrated than blood when water is scarce. The loop of Henle makes this possible. Its descending limb is permeable to water; its ascending limb pumps out salt but is impermeable to water. Together they build up a steep salt concentration in the tissue deep in the kidney (the medulla), with urea adding to it. This arrangement is called a countercurrent multiplier.

Later, when urine flows through the collecting duct, which passes through this salty region, water can be drawn out by osmosis — if the duct walls let it through.

Step 4: hormone control

The collecting duct is where the body decides how much water and salt to keep:

• ADH (antidiuretic hormone) inserts water channels, called aquaporins, into the duct walls. With ADH, water leaves the urine and returns to the blood, producing small volumes of concentrated urine. Without it, urine is dilute and plentiful (see water in the human body).
• Aldosterone increases sodium reabsorption and potassium secretion. More sodium kept means more water kept, raising blood volume and blood pressure.

The kidneys also act as hormone makers. When blood pressure falls, they release an enzyme called renin, which starts a cascade leading to aldosterone release and narrowing of blood vessels. They produce erythropoietin, which tells bone marrow to make red blood cells, and they convert vitamin D into its active form (see vitamin D chemistry).

Getting rid of nitrogen: urea

When the body breaks down amino acids, the nitrogen is removed as ammonia (NH₃), which is toxic even at low concentrations. The liver converts it into much less toxic urea through a series of reactions called the urea cycle (or ornithine cycle), discovered by Hans Krebs and Kurt Henseleit in 1932:

2NH₃ + CO₂ → CO(NH₂)₂ + H₂O (overall; the real pathway uses ATP and several intermediates)

Urea is small, uncharged and very water-soluble, so it’s easy to filter and excrete. An adult typically excretes around 20–35 g of urea a day, depending on protein intake. Urea is historically famous too: in 1828 Friedrich Wöhler made it from ammonium cyanate, an inorganic salt, challenging the idea that organic compounds could only be made by living things.

Other waste products the kidneys excrete include creatinine from muscle and uric acid from the breakdown of purines (see nucleic acids).

Controlling blood pH

Metabolism produces acids constantly — carbon dioxide, and non-volatile acids such as sulfuric acid from the sulfur in amino acids. The lungs remove CO₂; the kidneys handle the rest. They:

1. Reclaim filtered hydrogencarbonate (HCO₃⁻).
2. Secrete H⁺ into the urine, generating new HCO₃⁻ for the blood.
3. Buffer the secreted acid in urine using phosphate (HPO₄²⁻ + H⁺ → H₂PO₄⁻) and ammonia (NH₃ + H⁺ → NH₄⁺), so urine pH doesn’t fall too low.

This is why urine pH varies widely — from about 4.5 to 8 — while blood pH stays near 7.4 (see the blood buffer system). It’s also why diets can change urine pH without changing blood pH (see biochemistry myths).

Why urine is yellow

Urine’s colour comes mainly from urobilin, a breakdown product of haem from old red blood cells. The more dilute the urine, the paler it looks — a quick guide to hydration.

When chemistry precipitates: kidney stones

Urine carries many dissolved ions. If their concentrations exceed their solubility, solids can crystallise — forming kidney stones. The most common type is calcium oxalate, a very poorly soluble salt. Others include calcium phosphate, uric acid and struvite (magnesium ammonium phosphate, linked to certain infections).

Risk rises when urine is concentrated (not drinking enough), when there’s a lot of calcium, oxalate or uric acid, and when there’s too little citrate, a natural inhibitor that binds calcium and stops crystals growing. Drinking plenty of water is the simplest prevention: dilute the ions and they stay dissolved. Uric acid stones are more likely in acidic urine, because uric acid is less soluble in its un-ionised form — so making urine more alkaline can help dissolve them.

Dialysis: an artificial kidney

When kidneys fail, waste and potassium build up, acids accumulate and fluid is retained. Haemodialysis replaces the filtering step using diffusion across a semi-permeable membrane. Blood flows on one side of a membrane; on the other flows dialysis fluid containing the right concentrations of glucose and ions but no urea or creatinine. Waste diffuses from high concentration (blood) to low (fluid), while useful substances don’t, because their concentrations are the same on both sides. Blood flows one way and fluid the other (countercurrent), keeping a concentration gradient along the whole membrane.

Key takeaways

• Kidneys filter about 180 L a day by size and charge, then reabsorb about 99 %.
• The proximal tubule reclaims glucose, amino acids, salt and water, driven by the Na⁺/K⁺ pump.
• The loop of Henle builds a salt gradient; ADH and aldosterone fine-tune water and salt.
• Nitrogen leaves as urea, made in the liver; the kidneys also secrete acid to keep blood pH steady.
• Stones form when ions exceed their solubility; dialysis uses diffusion to remove waste.