Glomerular filtration

9 min read Last updated April 8, 2026

Clinical relevance (anaesthesia/ICU)

  • GFR determines clearance of many drugs/metabolites and influences fluid, electrolyte and acid–base homeostasis.
    • Falling GFR → reduced drug clearance (e.g. morphine metabolites, many antibiotics), hyperkalaemia risk, metabolic acidosis, fluid overload.
  • Renal hypoperfusion (hypotension, hypovolaemia, raised intra-abdominal pressure) can reduce GFR even if urine output is initially preserved by tubular handling.
    • Oliguria is not synonymous with low GFR; early AKI can be non-oliguric.
  • Anaesthetic drugs and techniques alter renal haemodynamics indirectly via MAP, sympathetic tone, CO2, and neurohormonal responses.
    • Volatile agents: generally preserve renal autoregulation at clinical doses; reductions in GFR usually due to reduced MAP/CO.
    • Neuraxial anaesthesia: sympathetic blockade → reduced renal perfusion pressure if MAP falls; treat hypotension promptly.
  • Perioperative factors that reduce GFR: hypovolaemia, sepsis, heart failure, increased renal venous pressure, abdominal compartment syndrome, nephrotoxins (NSAIDs, ACEi/ARB in certain contexts, contrast, aminoglycosides).
    • NSAIDs reduce prostaglandin-mediated afferent dilation → fall in GFR (especially in hypovolaemia/CKD).
    • ACEi/ARB reduce angiotensin II-mediated efferent constriction → fall in GFR (especially renal artery stenosis, hypovolaemia).

How to interpret common bedside data

  • Creatinine: rises late; depends on muscle mass and volume of distribution; not a direct real-time measure of GFR.
    • A small absolute rise may reflect a large fall in GFR when baseline creatinine is low.
  • Urine output: influenced by ADH, aldosterone, osmotic load, diuretics; interpret with haemodynamics and trend.
    • Diuretics increase urine output without improving GFR.
  • eGFR equations (CKD-EPI): estimate steady-state GFR; unreliable in acute changes, extremes of body habitus, pregnancy.
    • Use measured creatinine clearance or timed urine collections when accuracy is critical (still has limitations).

Definition and normal values

  • Glomerular filtration rate (GFR) = volume of plasma ultrafiltrate formed by all glomeruli per unit time.
  • Normal adult GFR: ~120 mL/min/1.73 m² (varies with age, sex, body size).
  • Renal plasma flow (RPF) ~600 mL/min; renal blood flow (RBF) ~1.2 L/min (~20–25% CO).
  • Filtration fraction (FF) = GFR/RPF ≈ 0.20 (20%).

Glomerular filtration barrier and selectivity

  • Barrier layers: fenestrated endothelium + glomerular basement membrane + podocyte slit diaphragm.
  • Selectivity is based on size and charge: negatively charged basement membrane restricts albumin and other anions.
    • Proteinuria suggests barrier damage or altered permselectivity (e.g. minimal change disease: loss of charge selectivity).
  • Cells are normally excluded; small solutes (Na+, glucose, urea) are freely filtered (sieving coefficient ~1).

Starling forces and the filtration equation

  • Net filtration pressure (NFP) across glomerular capillary = (Pgc − Pbs) − (πgc − πbs).
    • Pgc: glomerular capillary hydrostatic pressure (promotes filtration).
    • Pbs: Bowman’s space hydrostatic pressure (opposes filtration).
    • πgc: glomerular capillary oncotic pressure (opposes filtration; rises along capillary as proteins concentrate).
    • πbs: Bowman’s space oncotic pressure (normally ~0; increases if protein leaks into filtrate).
  • GFR = Kf × NFP, where Kf (filtration coefficient) = permeability × surface area.
    • Kf decreases with glomerular disease (reduced surface area/permeability) → reduced GFR.
  • Typical values (approx.): Pgc ~55 mmHg; Pbs ~15 mmHg; πgc ~30 mmHg → NFP ~10 mmHg.

Determinants of GFR: arteriolar tone and haemodynamics

  • Afferent arteriolar constriction ↓Pgc → ↓GFR and ↓RPF.
    • Causes: sympathetic stimulation (α1), adenosine (tubuloglomerular feedback), NSAIDs (loss of prostaglandin dilation).
  • Afferent arteriolar dilation ↑Pgc → ↑GFR and ↑RPF.
    • Mediators: prostaglandins (PGE2/PGI2), nitric oxide; low-dose dopamine is not recommended for renal protection.
  • Efferent arteriolar constriction: tends to ↑Pgc and ↑GFR initially but ↓RPF and ↑FF; if severe, πgc rises markedly and GFR may fall.
    • Angiotensin II preferentially constricts efferent arteriole (especially at low/moderate levels).
  • Efferent arteriolar dilation ↓Pgc → ↓GFR and ↑RPF (↓FF).
    • ACEi/ARB reduce efferent tone → may precipitate fall in GFR in renal artery stenosis or hypovolaemia.
  • Renal venous pressure and intra-abdominal pressure: increased values raise Pbs and reduce renal perfusion gradient → ↓GFR.
    • Seen in right heart failure, high PEEP with venous congestion, abdominal compartment syndrome.

Autoregulation of renal blood flow and GFR

  • Autoregulation maintains relatively constant RBF and GFR over a MAP range ~80–180 mmHg (shifted right in chronic hypertension).
  • Myogenic response: afferent arteriole constricts when stretched (↑MAP) and dilates when pressure falls.
  • Tubuloglomerular feedback: macula densa senses distal tubular NaCl delivery (via NKCC2) and adjusts afferent tone and renin release.
    • High NaCl delivery → adenosine/ATP → afferent constriction → ↓GFR.
    • Low NaCl delivery → renin release → angiotensin II (efferent constriction) + afferent dilation → support GFR.
  • Sympathetic activation (stress, hypovolaemia): constricts afferent and efferent arterioles, reduces RBF; GFR may be preserved initially by efferent constriction but falls if severe.

Measurement of GFR and related concepts

  • Clearance principle: Cx = (Ux × V) / Px (mL/min).
  • Ideal GFR marker: freely filtered, not reabsorbed/secreted/metabolised, not protein-bound, inert.
  • Inulin clearance: gold standard (measures GFR) but impractical clinically.
  • Creatinine clearance: approximates GFR but overestimates due to tubular secretion (more in CKD).
    • Cimetidine/trimethoprim inhibit creatinine secretion → serum creatinine rises without true fall in GFR.
  • Urea: filtered and reabsorbed; clearance underestimates GFR and varies with hydration/ADH.
  • PAH clearance estimates effective renal plasma flow (ERPF) because PAH is filtered and strongly secreted (near-complete extraction at low plasma concentrations).
    • ERPF < true RPF because extraction ratio <1 and not all renal blood flow perfuses secreting tubules.

Factors altering GFR (common exam list)

  • Increase GFR: afferent dilation, mild efferent constriction, increased Kf (rare physiologically), reduced πgc (hypoproteinaemia), pregnancy (↑RPF and Kf).
  • Decrease GFR: afferent constriction, efferent dilation, reduced Kf (glomerular disease), increased Pbs (obstruction), increased πgc (dehydration/high plasma proteins), reduced MAP below autoregulatory range.
    • Post-renal obstruction increases Pbs rapidly → reduced GFR; bilateral obstruction or solitary kidney obstruction is clinically significant.
  • Effect of plasma proteins: higher plasma oncotic pressure (πgc) opposes filtration → lower GFR; lower proteins can increase GFR but may reduce effective circulating volume and renal perfusion in disease states.
Define GFR and give normal values. How does it relate to renal blood flow and filtration fraction?

A common opening renal physiology viva: definitions, normal numbers, and relationships.

  • GFR = volume of ultrafiltrate formed per unit time by all glomeruli.
  • Normal: ~120 mL/min/1.73 m² in a healthy young adult (declines with age).
  • RBF ~1.2 L/min (~20–25% CO); RPF ~600 mL/min.
  • Filtration fraction FF = GFR/RPF ≈ 0.20 (20%).
Write the Starling equation for net filtration pressure across the glomerulus and explain each term.

Examiners often want the equation and physiological meaning, not just the words.

  • NFP = (Pgc − Pbs) − (πgc − πbs).
  • Pgc promotes filtration; Pbs opposes filtration; πgc opposes filtration; πbs is normally ~0 (increases if protein leaks).
  • GFR = Kf × NFP; Kf reflects permeability and surface area.
How do changes in afferent and efferent arteriolar resistance affect GFR, RPF and filtration fraction?

This is frequently examined: directional changes and the concept of severe efferent constriction.

  • Afferent constriction: ↓Pgc → ↓GFR, ↓RPF, FF often ~unchanged or may fall slightly.
  • Afferent dilation: ↑Pgc → ↑GFR, ↑RPF, FF variable (often little change).
  • Efferent constriction (mild/moderate): ↑Pgc → ↑GFR, ↓RPF → ↑FF.
  • Efferent constriction (severe): marked ↓RPF → large rise in πgc along capillary; GFR may fall despite high Pgc.
  • Efferent dilation: ↓Pgc → ↓GFR, ↑RPF → ↓FF.
Describe renal autoregulation and the mechanisms involved. What happens in chronic hypertension?

Expect MAP range plus myogenic and tubuloglomerular feedback; then the rightward shift concept.

  • Autoregulation maintains near-constant RBF and GFR over MAP ~80–180 mmHg (approximate).
  • Myogenic: afferent arteriole constricts with stretch (↑MAP) and dilates when pressure falls.
  • Tubuloglomerular feedback: macula densa senses distal NaCl; high NaCl → adenosine/ATP → afferent constriction; low NaCl → renin release → angiotensin II supports GFR.
  • Chronic hypertension: autoregulatory curve shifts right; kidneys tolerate higher pressures but are more vulnerable to 'normal' MAPs intraoperatively (relative hypotension).
How do NSAIDs and ACE inhibitors/ARBs reduce GFR? In which patients is this most clinically important?

A classic applied physiology question linking arteriolar tone to drugs.

  • NSAIDs inhibit prostaglandins → loss of afferent arteriolar dilation → afferent constriction → ↓Pgc and ↓GFR.
  • ACEi/ARB reduce angiotensin II → efferent arteriolar dilation → ↓Pgc and ↓GFR (especially when renal perfusion is pressure-dependent).
  • High-risk contexts: hypovolaemia, sepsis, heart failure, CKD, renal artery stenosis (bilateral or solitary kidney).
Explain how urinary tract obstruction reduces GFR using the filtration equation.

Examiners look for Pbs and the downstream effect on NFP.

  • Obstruction increases hydrostatic pressure in Bowman’s space (Pbs).
  • NFP = (Pgc − Pbs) − (πgc − πbs): increasing Pbs reduces NFP → reduces GFR.
  • Clinically significant when bilateral obstruction or obstruction of a solitary functioning kidney.
Describe how GFR is measured using clearance. What properties should an ideal marker have?

Often asked as a structured answer: formula then ideal marker criteria.

  • Clearance of substance X: Cx = (Ux × V) / Px.
  • Ideal GFR marker: freely filtered; not reabsorbed; not secreted; not metabolised/synthesised by kidney; not protein-bound; inert and non-toxic.
  • Inulin fits best (gold standard) but is impractical; creatinine clearance is used clinically but overestimates GFR due to secretion.
Why does creatinine clearance overestimate GFR? Name drugs/conditions that alter serum creatinine without changing true GFR.

This tests understanding of tubular secretion and assay/handling confounders.

  • Creatinine is filtered and also secreted by proximal tubule → urinary excretion exceeds filtered load → clearance slightly > true GFR (more so in CKD).
  • Trimethoprim and cimetidine inhibit creatinine secretion → serum creatinine rises without true fall in GFR.
  • Creatinine depends on muscle mass, diet, and volume status; eGFR is unreliable in acute kidney injury (non-steady state).
What is filtration fraction? How does it change with efferent arteriolar constriction and why does that matter physiologically?

Links haemodynamics to peritubular capillary forces and proximal reabsorption.

  • FF = GFR/RPF (normally ~0.20).
  • Efferent constriction reduces RPF and tends to increase GFR initially → FF increases.
  • Higher FF concentrates plasma proteins in efferent/peritubular capillaries → increases peritubular oncotic pressure, promoting proximal tubular reabsorption of Na+ and water.
Describe tubuloglomerular feedback in detail: what is sensed, where, and what mediators are involved?

A detailed mechanism question that commonly appears in written/viva formats.

  • Sensor: macula densa cells in the distal tubule (juxtaglomerular apparatus) sense luminal NaCl via NKCC2 transporter.
  • High NaCl delivery (high flow/high GFR) → release of ATP/adenosine → afferent arteriolar constriction → reduces GFR.
  • Low NaCl delivery → stimulates renin release from JG cells → angiotensin II (preferential efferent constriction) and supports GFR; also promotes Na+ retention.
Previous FRCA-style question: 'Describe the factors that determine glomerular filtration rate and how it is regulated.' Provide a structured answer.

A typical long-form physiology question: definition, equation, determinants, regulation, and measurement/clinical links.

  • Start with definition and normal value; then state GFR = Kf × [(Pgc − Pbs) − (πgc − πbs)].
  • Determinants: Kf (surface area/permeability), Pgc (arteriolar tone/MAP), Pbs (obstruction/venous pressure), πgc (plasma proteins, rises along capillary), πbs (normally ~0).
  • Regulation: autoregulation (myogenic + tubuloglomerular feedback), sympathetic nervous system, RAAS, prostaglandins/NO; explain afferent vs efferent effects.
  • Clinical modifiers: NSAIDs (afferent), ACEi/ARB (efferent), hypovolaemia/sepsis, raised intra-abdominal pressure, renal venous congestion; link to perioperative AKI risk.

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