The Kidneys Filtering System – Including Hypertension

This page has all the details below the summary, this is a fundamental aspect of health that is not usually understood as the drug industry usually only addresses reducing the symptoms, for example with hypertension and T2DM.

The Summary:

Your kidneys filter 180 litres of fluid every day through tiny filters. This filtrate contains all your body’s sodium, glucose, and nutrients mixed with waste products. The tubules are recovery tubes that reclaim 99% of the good stuff and send it back into your blood. Only 1-2 litres of concentrated waste becomes urine.
Insulin normally helps the tubules hold onto sodium after meals (so you don’t urinate excessively after eating). But when you have insulin resistance, insulin is high ALL THE TIME, so your tubules ALWAYS hold onto sodium. This extra sodium pulls water into your blood, expanding blood volume and raising blood pressure.
When we reverse insulin resistance and lower your insulin levels, your tubules finally START LETTING GO of the excess sodium. Within 2-4 weeks, you’ll pee out litres of retained fluid, blood pressure drops, and many people come off medications entirely.

THE KIDNEY’S FILTRATION & RECOVERY SYSTEM

PART 1: WHY TUBULES EXIST – THE KIDNEY’S DILEMMA

The Problem:
Your kidneys face a massive challenge every day:
– They filter 180 litres (47 gallons) of blood plasma through tiny filters called glomeruli
– This creates 180 litres of “filtrate” (pre-urine) that contains:
ALL the waste products (urea, creatinine, toxins) ✓ (want to  excrete)
But ALSO all the good stuff: sodium, potassium, glucose, amino acids, water ✗ (want to keep!)
If kidneys just dumped all 180 litres:
– You’d urinate 180 litres/day (death by dehydration in hours)
– You’d lose ALL your sodium (death)
– You’d lose ALL your glucose (death)
– You’d lose ALL your amino acids (death)
The Solution: TUBULES
The tubules are recovery tubes that:
– Start with 180 litres of filtrate containing everything (waste + – good stuff)
– Selectively reabsorb 99%+ of the good stuff back into the blood
– Leave waste products behind
End with only ~1-2 litres of urine containing concentrated waste
Think of it like a recycling centre:
Filtration = Dump everything in the bin
Tubules = Sort through and rescue what’s valuable
Urine = What’s left (actual rubbish)

PART 2: WHAT THE TUBULES REABSORB (AND WHERE)
The tubules are divided into segments, each specialised for recovering specific substances:

PROXIMAL CONVOLUTED TUBULE (PCT) – The Workhorse
Location: First segment, right after the filter
Length: ~15mm
Job: Recover 65-70% of EVERYTHING
What it reabsorbs:
– 65% of filtered sodium (~25,000 mmol/day filtered, recovers ~16,250 mmol)
– 65% of filtered water (drives osmotically with sodium)
– 100% of glucose (via sodium-glucose cotransporters – SGLT2)
– 100% of amino acids
85-90% of bicarbonate (keeps blood pH stable)
– Calcium, magnesium, phosphate, potassium
How it works:
– Sodium is the DRIVING FORCE for everything else
– Na+/K+-ATPase pumps on the cell wall create a sodium gradient
– This gradient pulls sodium IN from the filtrate
– Sodium drags water, glucose, amino acids with it (co-transport)
– Everything goes back into the blood
Result: Filtrate volume drops from 180L → 60L

LOOP OF HENLE – The Concentrator
Location: U-shaped loop diving deep into kidney
Job: Create concentration gradient for water recovery
What it reabsorbs:
– 25% of filtered sodium (thick ascending limb via NKCC2 transporter)
– 20% of filtered water (descending limb only – water follows salt)
– Special feature:
– Creates hyperosmotic environment in kidney medulla
– This allows collecting duct to concentrate urine later
Result: Filtrate volume drops from 60L → 20L

DISTAL CONVOLUTED TUBULE (DCT) – The Fine-Tuner
Location: After loop of Henle, before collecting duct
Length: ~5mm
Job: Precision control of sodium, potassium, calcium
What it reabsorbs:
– 5-10% of filtered sodium (via NCC transporter – thiazide drug target)
– Calcium (vitamin D regulated)
– Magnesium
– What it secretes:
– Potassium (exchanged for sodium)
Result: Filtrate volume drops from 20L → 10L

COLLECTING DUCT (CD) – The Final Regulator
Location: Final segment before urine exits
Job: Last chance to save/dump water and sodium based on body needs
What it reabsorbs:
– 2-5% of filtered sodium (via ENaC channels – amiloride drug target)
– 5-24% of remaining water (depends on vasopressin/ADH hormone)
CRITICAL FEATURE:
– This is the FINAL CONTROL POINT for body sodium
– Once sodium leaves here, it’s gone forever (into bladder)
– Heavily regulated by:
– Aldosterone (increases sodium recovery, dumps potassium)
– Vasopressin/ADH (increases water recovery)
INSULIN (increases sodium recovery) ← KEY FOR HYPERTENSION
Result: Final urine = 1-2 litres/day

SUMMARY OF REABSORPTION ALONG THE NEPHRON:

PART 3: WHY INSULIN AFFECTS THE TUBULES
Insulin Receptors Are Present Throughout the Entire Nephron
Where insulin receptors are found:
– Proximal convoluted tubule ✓
– Loop of Henle (thick ascending limb) ✓
– Distal convoluted tubule ✓
– Collecting duct ✓
Why kidneys have insulin receptors:
EVOLUTIONARY REASON:
– After eating, insulin rises (fed state)
– Body wants to CONSERVE sodium and water (prevent excess urination after meals)
– Insulin signals: “We just ate, hold onto sodium/water, don’t waste it”
– This is PROTECTIVE when insulin is pulsatile (spikes after meals, drops between meals)
THE PROBLEM IN INSULIN RESISTANCE:
– Insulin is chronically elevated 24/7 (not just after meals)
– Kidneys think you’re in a perpetual fed state
– They retain sodium ALL THE TIME (not just post-meal)
– Result: Chronic sodium retention → Fluid overload → Hypertension

PART 4: HOW INSULIN INCREASES SODIUM RETENTION
Insulin Acts on Multiple Tubule Segments:

1. PROXIMAL TUBULE (65% of sodium reabsorption)
Insulin activates:
NHE3 (Na+/H+ exchanger) – increases sodium reabsorption
Na+/K+-ATPase – increases basolateral sodium pumping
SGLT2 (sodium-glucose cotransporter) – pulls sodium + glucose together
Mechanism:
Insulin binds to insulin receptor (INSR)
Activates IRS2 (insulin receptor substrate 2) pathway
Stimulates mTORC2/SGK1 signaling
Result: MORE sodium reabsorbed, LESS sodium delivered to distal tubule
Net effect: Keeps extra 2-5% of filtered sodium (~500-1,250 mmol)

2. LOOP OF HENLE (25% of sodium reabsorption)
Insulin activates:
NKCC2 (Na+/K+/2Cl− cotransporter) – thick ascending limb
Na+/K+-ATPase – increases basolateral pumping
Mechanism:
Insulin (and C-peptide) stimulates protein kinase C (PKC) pathway
Phosphorylates Na+/K+-ATPase α-subunit
Increases NKCC2 expression and activity
Net effect: Keeps extra 1-2% of filtered sodium (~250-500 mmol)

3. DISTAL CONVOLUTED TUBULE (5-10% of sodium reabsorption)
Insulin activates:
NCC (Na+/Cl− cotransporter) – phosphorylation increases activity
WNK kinases – master regulators of NCC and ENaC
Mechanism:
Insulin activates WNK1, WNK3, WNK4 kinases
These phosphorylate NCC (increases activity)
More sodium reabsorbed from passing filtrate
Net effect: Keeps extra 0.5-1% of filtered sodium (~125-250 mmol)

4. COLLECTING DUCT (2-5% of sodium reabsorption) – MOST IMPORTANT
Insulin activates:
ENaC (epithelial sodium channels) – final control point
Na+/K+-ATPase – basolateral pump
Mechanism:
Insulin binds to insulin receptor on principal cells
Activates PI3-kinase → mTOR pathway
Increases ENaC channel open probability (Po) (channels open more frequently)
Does NOT increase number of channels, just makes existing ones work harder
CRITICAL EXPERIMENTAL EVIDENCE:
Mice with collecting duct insulin receptor knockout:
Have LOWER blood pressure than normal mice
Excrete MORE sodium in urine
Cannot respond to insulin with sodium retention
THIS PROVES insulin directly causes sodium retention via kidney insulin receptors
Net effect: This is the FINAL regulatory step – keeps extra 0.5-2% of filtered sodium

TOTAL EFFECT OF HIGH INSULIN:
When insulin is chronically elevated (insulin resistance):
NORMAL sodium excretion: 1-3% of filtered (~250-750 mmol/day)
WITH HYPERINSULINEMIA:
– Proximal tubule: +500-1,250 mmol retained
– Loop of Henle: +250-500 mmol retained
– Distal tubule: +125-250 mmol retained
– Collecting duct: +125-500 mmol retained
TOTAL EXTRA SODIUM RETAINED: 1,000-2,500 mmol
– 1,000 mmol sodium = 23,000mg = 58g table salt
– Where does this sodium go?
– Into extracellular fluid
– Draws water osmotically (each mmol Na+ pulls ~10ml water)
– 1,000 mmol sodium → +10 litres of fluid retention
– More fluid volume → Higher blood pressure

PART 5: THE “SELECTIVE INSULIN RESISTANCE” PARADOX
Why This Matters:
In insulin-resistant patients:
❌ Muscles are insulin resistant (can’t take up glucose)

❌ Liver is insulin resistant (keeps making glucose despite high insulin)

❌ Fat cells are insulin resistant (can’t store fat properly)
✅ KIDNEYS REMAIN INSULIN SENSITIVE (still respond to insulin’s sodium-retaining signals)
THIS IS THE MECHANISM OF HYPERTENSION IN INSULIN RESISTANCE
The research shows:
– Kidney IRS2 expression (sodium reabsorption pathway) is PRESERVED in insulin resistance
– Muscle/liver IRS1 expression (glucose metabolism pathway) is IMPAIRED in insulin resistance
– Kidneys use IRS2 for sodium transport (not affected by insulin resistance)
– Muscles use IRS1 for glucose uptake (destroyed by insulin resistance)
Result:
– High insulin → Kidneys still respond → Retain sodium → Hypertension
High insulin → Muscles don’t respond → Can’t store glucose → High blood sugar
THIS IS WHY:
– You can have Type 2 diabetes (muscle insulin resistance) AND hypertension (kidney insulin sensitivity) simultaneously
– Lowering insulin fixes BOTH problems at once

THE BOTTOM LINE:

1. Why does insulin affect the tubules?
Tubules have insulin receptors throughout (evolutionary design for post-meal sodium conservation)
Insulin signals “fed state” → “conserve sodium”
Problem: Chronic high insulin = chronic “fed state” signal
2. Why do tubules collect things?
Kidneys filter 180L/day (would die if you peed it all out)
Tubules recover 99% of everything valuable (sodium, water, glucose, amino acids)
Only 1% becomes urine (concentrated waste)
3. What do they collect?
65% sodium (proximal tubule)
25% sodium (loop of Henle)
5-10% sodium (distal tubule)
2-5% sodium (collecting duct)
TOTAL: 97-99% of filtered sodium is reabsorbed
100% glucose (proximal tubule – explains why diabetics pee sugar when overwhelmed)
100% amino acids
99% water
Bicarbonate, calcium, magnesium, potassium