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Human Physiology · Renal system

Glomerular Filtration and Renal Blood Flow

Every day your kidneys filter about 180 litres of plasma and return almost all of it. This page explains how the kidney is supplied with blood, how filtration works and is controlled, how kidney function is measured, and what this means for exercise and muscle injury.

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Part 5 · Renal System · Chapter 21 of 47

Learning objectives

By the end of this page you should be able to:

  • List the functions of the kidney and describe the nephron.
  • Describe renal blood flow and the glomerular filtration barrier.
  • Explain the forces that drive filtration and how GFR is controlled.
  • Explain clearance and how eGFR is estimated.
  • Describe how rhabdomyolysis injures the kidney.
  • Summarise the evidence for exercise in chronic kidney disease.

Why it matters

Kidney disease is common among the patients physiotherapists treat: people with diabetes, hypertension, heart failure and older adults. Many are deconditioned and benefit from exercise.

Physiotherapists also need to recognise exertional muscle breakdown, which can damage the kidneys after unaccustomed intense exercise, crush injury or prolonged lying after a fall.

What the kidneys do

FunctionExamples
ExcretionUrea, creatinine, uric acid, drugs
Water and salt balanceControl of blood volume and blood pressure
Electrolyte balancePotassium, calcium, phosphate
Acid–base balanceExcrete acid, regenerate bicarbonate
HormonesErythropoietin (red cells), renin, active vitamin D

The nephron and renal blood flow

Figure 1 · The nephron

Schematic nephron from glomerulus to collecting duct An afferent arteriole enters a glomerulus inside Bowman’s capsule and an efferent arteriole leaves. Filtrate passes through the proximal tubule, the loop of Henle dipping into the medulla, the distal tubule and the collecting duct, which delivers urine. afferentefferent arterioleGlomerulus in Bowman’s capsuleProximal tubulereabsorbs about two thirdsLoop ofHenleDistal tubuleCollectingductfinal wateradjustmenturinemedullacortexmedulla
About a million in each kidney. The glomerulus filters; the tubule decides what to keep. Schematic, not to scale.

The kidneys receive about 1.1 litres of blood per minute, roughly a fifth of cardiac output at rest, though they make up less than 1% of body weight. Each nephron begins at a glomerulus, a tuft of capillaries between two arterioles: the afferent arteriole in and the efferent arteriole out.

Having resistance on both sides of the glomerulus keeps glomerular capillary pressure high, which suits filtration. After the efferent arteriole, blood flows through a second capillary network around the tubules.

The filtration barrier

LayerStructureWhat it stops
EndotheliumFenestrated capillary cellsBlood cells
Basement membraneNegatively charged meshworkLarge and negatively charged proteins
PodocytesInterlocking foot processes with slit diaphragmsMedium-sized proteins such as albumin

Water, glucose, salts, urea and other small molecules pass freely. Albumin is largely held back by size and charge. Protein in the urine is therefore an early sign of glomerular damage, as in diabetes and hypertension.

Forces of filtration

Figure 2 · The forces that drive filtration

Starling forces across the glomerular capillary Four bars. Glomerular capillary pressure of about 55 millimetres of mercury pushes fluid out. Bowman’s capsule pressure of about 15 and plasma oncotic pressure of about 30 oppose it. The net filtration pressure is about 10. 55 mmHgGlomerular capillarypressurepushes out15 mmHgBowman’s capsulepressurepushes back30 mmHgPlasma oncoticpressureholds fluid in10 mmHgNet filtrationpressure= 55 − 15 − 30
A small net pressure over a huge, leaky surface. Glomerular capillary pressure is high because the efferent arteriole also offers resistance. Typical textbook values.

Filtration follows the same Starling forces met in Chapter 14, but the glomerulus is unusual. Its capillary pressure is high, its barrier is very permeable, and its surface area is large. A net pressure of only about 10 mmHg produces a filtration rate of about 125 mL/min.

That is about 180 litres a day. Since plasma volume is about 3 litres, the whole plasma is filtered roughly 60 times a day. About a fifth of the plasma reaching the glomerulus is filtered; this is the filtration fraction.

Control of GFR

ChangeEffect on glomerular pressureEffect on GFR
Afferent arteriole constrictsFallsFalls
Afferent arteriole dilatesRisesRises
Efferent arteriole constricts (moderate)RisesRises
Low plasma proteinLess opposing oncotic pressureRises
Ureter blockedCapsule pressure risesFalls

Figure 3 · Renal autoregulation

Renal blood flow and filtration rate against mean arterial pressure Renal blood flow and filtration rise with pressure below about 80 millimetres of mercury, stay nearly constant between about 80 and 180, and rise again above that. autoregulated range: about 80–180 mmHg4080120160200Mean arterial pressure (mmHg)Renal blood flow and GFRTwo mechanisms:myogenic responseof the afferentarterioletubuloglomerularfeedback (maculadensa)
Filtration is protected from everyday swings in blood pressure. Below the range, as in shock or severe dehydration, filtration falls. Schematic.

Two local mechanisms keep GFR steady. The myogenic response constricts the afferent arteriole when pressure stretches it. In tubuloglomerular feedback, cells of the macula densa sense salt delivery to the distal tubule and adjust afferent tone.

Sympathetic activity, for example in heavy exercise or haemorrhage, constricts renal arterioles and lowers renal blood flow. Angiotensin II constricts the efferent arteriole more than the afferent, which helps hold GFR when blood pressure is low.

Exercise, dehydration and anti-inflammatory drugs

Prostaglandins help keep the afferent arteriole open when renal blood flow is reduced. Non-steroidal anti-inflammatory drugs block them. Combining these drugs with dehydration and prolonged hard exercise increases the risk of kidney injury.

Measuring kidney function

The clearance of a substance is the volume of plasma completely cleared of it per minute. A substance that is freely filtered and neither reabsorbed nor secreted, such as inulin, has a clearance equal to GFR.

In practice, GFR is estimated from blood creatinine, a waste product of muscle. Levey and colleagues developed the CKD-EPI equation, which estimated GFR more accurately than the earlier MDRD equation, especially at higher values [1].

Figure 4 · Categories of kidney function

Estimated GFR categories from G1 to G5 A horizontal band divided into six categories of estimated filtration rate: G1 90 or more, G2 60 to 89, G3a 45 to 59, G3b 30 to 44, G4 15 to 29 and G5 under 15 millilitres per minute per 1.73 square metres. G190 or morenormal/high*G260–89mild*G3a45–59mild–modG3b30–44mod–severeG415–29severeG5under 15failureEstimated GFR (mL/min/1.73 m²)* G1 and G2 count as chronic kidney disease only with other markers of kidney damageEstimated from blood creatinine, age and sex by equation [1]
eGFR is an estimate. Equations convert a creatinine value into a filtration rate [1]. Muscle mass affects creatinine, so very muscular or very frail patients may be misclassified.

The equation’s developers noted limited data for older people and some population groups [1]. Because creatinine comes from muscle, estimates can be misleading in people with very large or very small muscle mass, such as amputees, bodybuilders or frail older adults. Equations have since been revised; use the one your laboratory reports.

Rhabdomyolysis and acute kidney injury

Rhabdomyolysis is the breakdown of skeletal muscle with release of its contents into the blood. Myoglobin damages the kidney tubules, especially when the patient is dehydrated and the urine is acidic [2]. Potassium release can cause dangerous heart rhythms [2].

Cause [2]Example relevant to physiotherapy
Unaccustomed intense exerciseFirst high-intensity class, eccentric overload, exercise in heat
Crush or prolonged immobilityLong lie after a fall, prolonged surgery
Drugs and toxinsStatins, alcohol, some recreational drugs
Heat illnessExertional heat stroke
Seizures and electrolyte disordersLow potassium or phosphate

Red flags after exercise

Muscle pain and swelling out of proportion to the session, marked weakness and dark, tea-coloured urine suggest rhabdomyolysis [2]. Stop exercise, encourage fluids if allowed, and arrange urgent medical assessment, including creatine kinase and kidney function.

Exercise in chronic kidney disease

People with chronic kidney disease are often very deconditioned. Heiwe and Jacobson reviewed 45 trials in 1,863 adults with CKD or kidney transplants [3].

Figure 5 · Exercise in chronic kidney disease

Pooled effects of regular exercise in adults with chronic kidney disease Five results: improved aerobic capacity and walking capacity, systolic blood pressure about 6.1 millimetres of mercury lower, resting heart rate about 6 beats per minute lower, and improved health-related quality of life. Aerobic capacityimproved (SMD 0.56)Walking capacityimproved (SMD 0.36)Resting systolic BP6.1 mmHg lowerResting heart rate6 beats/min lowerHealth-related quality of lifeimprovedRegular exercise versus control; 45 trials, 1,863 adults with CKD or kidney transplant [3]
Exercise is part of kidney care. Benefits were seen across aerobic, resistance and mixed programmes, though many trials had a high risk of bias [3].

Regular exercise improved aerobic and walking capacity, lowered resting blood pressure and heart rate, and improved quality of life [3]. Programmes included aerobic, resistance, mixed and yoga-based exercise, both supervised and home-based [3].

Practical skill · exercising patients on dialysis

Protect the arm with an arteriovenous fistula: no blood pressure cuff, tight straps or heavy loading on it. Exercise on non-dialysis days or early in a dialysis session, monitor blood pressure, and adjust for fluid shifts and fatigue.

Clinical relevance for the physiotherapist

  • Interpreting eGFR. Remember muscle mass affects creatinine-based estimates [1].
  • Exercise prescription. Exercise improves fitness, blood pressure and quality of life in CKD [3].
  • New intense programmes. Progress gradually, especially eccentric work and in heat, to avoid rhabdomyolysis [2].
  • Long lies and crush injury. Check for muscle breakdown before mobilising [2].
  • Drugs. Ask about anti-inflammatory use in dehydrated or older patients.

Assessment and application

SituationConcernAction
Dark urine and severe thigh pain two days after a first spin classRhabdomyolysis [2]Stop exercise; urgent medical review
eGFR 38 in a frail 85-year-oldCategory G3b, but creatinine may underestimate impairmentExercise with monitoring; review medications with team
Patient on haemodialysis, breathless and tiredDeconditioning, anaemia, fluid shiftsGraded aerobic and resistance training [3]
Older patient found on the floor after a nightCrush-related muscle breakdown [2]Medical check before mobilising

Common mistakes

  • Thinking GFR is controlled only by blood pressure; arteriolar tone matters.
  • Treating eGFR as a precise measurement [1].
  • Ignoring dark urine after an intense session [2].
  • Avoiding exercise in kidney disease [3].
  • Measuring blood pressure on a fistula arm.

Exam preparation

Long answer

Define glomerular filtration rate. Describe the factors that determine and regulate it.

  • Nephron and filtration barrier (Figure 1).
  • Starling forces and net filtration pressure (Figure 2).
  • Afferent and efferent arteriolar control (table).
  • Autoregulation: myogenic and tubuloglomerular feedback (Figure 3).
  • Measurement: clearance and eGFR [1].

Short notes

  • Filtration fraction.
  • Renal clearance.
  • Rhabdomyolysis [2].
  • Exercise in chronic kidney disease [3].

Viva and practical

  • “What is normal GFR?” — about 125 mL/min, 180 L/day.
  • “Why does efferent constriction raise GFR?” — it raises glomerular pressure.
  • “What does tea-coloured urine after exercise suggest?” — myoglobinuria [2].
  • OSCE: plan exercise for a patient on dialysis [3].

Current evidence

Exam and traditional teaching

Kidney patients are advised to rest; GFR is described mainly through inulin clearance.

What the evidence adds

eGFR equations such as CKD-EPI estimate function from creatinine with useful accuracy [1].

Regular exercise benefits adults with CKD [3], while sudden intense exercise can cause rhabdomyolysis [2].

What the student should understand

Protect the kidney from sudden insults, but do not protect it from exercise. Graded training is part of kidney care.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. The CKD-EPI equation estimates GFR from:
  1. (A) Urine colour
  2. (B) Serum creatinine with age and sex (and other variables)
  3. (C) Blood pressure
  4. (D) Haemoglobin

Answer: (B) The equation regresses measured GFR on standardised creatinine, sex, age and other variables [1].

Q2. Compared with the older MDRD equation, CKD-EPI was:
  1. (A) Less accurate
  2. (B) More accurate, especially at higher GFR
  3. (C) Identical
  4. (D) Only for children

Answer: (B) CKD-EPI showed less bias and greater accuracy, particularly at higher GFR [1].

Q3. The proportion of estimates within 30% of measured GFR with CKD-EPI was about:
  1. (A) 50%
  2. (B) 84%
  3. (C) 99%
  4. (D) 20%

Answer: (B) 84.1% of estimates fell within 30% of measured GFR [1].

Q4. Rhabdomyolysis can injure the kidney mainly through:
  1. (A) Release of myoglobin and other muscle contents
  2. (B) Excess vitamin D
  3. (C) Low blood glucose
  4. (D) Hair loss

Answer: (A) Muscle breakdown releases myoglobin that damages the kidney [2].

Q5. Which electrolyte disturbance is a dangerous early feature of rhabdomyolysis?
  1. (A) Hypokalaemia
  2. (B) Hyperkalaemia
  3. (C) Hypernatraemia
  4. (D) Hypercalcaemia only

Answer: (B) Potassium released from damaged muscle can cause hyperkalaemia [2].

Q6. A classic sign of significant rhabdomyolysis is:
  1. (A) Clear, pale urine
  2. (B) Dark, tea-coloured urine
  3. (C) Bradycardia
  4. (D) Increased muscle strength

Answer: (B) Myoglobinuria darkens the urine [2].

Q7. In adults with CKD, regular exercise improved aerobic capacity with a standardised mean difference of about:
  1. (A) 0.05
  2. (B) 0.56
  3. (C) 3.0
  4. (D) No effect

Answer: (B) Aerobic capacity improved, SMD about 0.56 [3].

Q8. Exercise in CKD lowered resting systolic blood pressure by about:
  1. (A) 0 mmHg
  2. (B) 6 mmHg
  3. (C) 30 mmHg
  4. (D) 60 mmHg

Answer: (B) Systolic pressure fell by about 6.08 mmHg [3].

Q9. How many trials did the Cochrane review of exercise in CKD include?
  1. (A) 5
  2. (B) 45
  3. (C) 450
  4. (D) 1

Answer: (B) Forty-five RCTs with 1,863 participants [3].

Q10. Because creatinine comes from muscle, eGFR may be misleading in:
  1. (A) Average adults
  2. (B) People with very high or very low muscle mass
  3. (C) Nobody
  4. (D) Only children under 1

Answer: (B) The equations assume typical creatinine generation; they had limited data in some groups, such as elderly people [1].

Quick review

Key takeaways

  • Kidneys get about 20% of cardiac output; GFR about 125 mL/min.
  • Net filtration pressure about 10 mmHg; filtration fraction about 20%.
  • Afferent and efferent arterioles control GFR; autoregulation 80–180 mmHg.
  • eGFR is estimated from creatinine by equation [1].
  • Rhabdomyolysis: muscle pain, weakness, dark urine; risk of kidney injury [2].
  • Exercise improves fitness and blood pressure in CKD [3].

Further reading

SourceWhy it earns its place
Levey AS et al. — Ann Intern Med, 2009The CKD-EPI equation [1]
Bosch X et al. — NEJM, 2009Rhabdomyolysis explained [2]
Heiwe S, Jacobson SH — Cochrane Review, 2011Exercise in CKD [3]
Eaton DC, Pooler JP — Vander’s Renal PhysiologyClear account of renal physiology

References

  1. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Annals of Internal Medicine. 2009;150(9):604–612. doi:10.7326/0003-4819-150-9-200905050-00006 PMID 19414839 Validation study
  2. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. New England Journal of Medicine. 2009;361(1):62–72. doi:10.1056/NEJMra0801327 PMID 19571284 Review
  3. Heiwe S, Jacobson SH. Exercise training for adults with chronic kidney disease. Cochrane Database of Systematic Reviews. 2011;(10):CD003236. doi:10.1002/14651858.CD003236.pub2 PMID 21975737 Cochrane review

Related topics

Reviewed by the Physiotherapist India Team. · Human Physiology contents