Step 1 · Renal

Glomerular Filtration & Clearance

Name: Glomerular Filtration & Clearance
Creator: Veli Bakalov, MD

Inulin, PAH, and the filtration fraction, plus how arterioles and drugs move GFR

Renal·Physiology·4 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Clearance = (U × V) / P; inulin (freely filtered, not reabsorbed or secreted) clearance equals GFR, the gold standard (~100–120 mL/min).
Creatinine clearance slightly overestimates GFR because creatinine is mildly secreted; serum creatinine rises as GFR falls.
PAH is filtered and secreted (cleared in one pass), so its clearance equals effective RPF (~600 mL/min); RBF = RPF / (1 − Hct).
Filtration fraction = GFR / RPF ≈ 20%; angiotensin II raises it and ACE inhibitors lower it.
Clearance below GFR = net reabsorption (glucose ~0, Na⁺, HCO₃⁻); above GFR = net secretion (PAH); equal to GFR = filtered only (inulin).
GFR = Kf × [(PGC − PBS) − (πGC − πBS)] with πBS ≈ 0; ureteral obstruction (↑ PBS) and high plasma protein (↑ πGC) lower GFR.
Afferent constriction (NSAIDs) lowers GFR and RPF with FF unchanged; efferent constriction (angiotensin II) raises GFR and FF while lowering RPF.
ACE inhibitors/ARBs dilate the efferent (↓ GFR, ↑ RPF, ↓ FF): AKI in bilateral renal artery stenosis, renoprotection in diabetic nephropathy; NSAID + ACE inhibitor + diuretic is the "triple whammy."
Autoregulation (MAP ~80–180 mmHg) uses the myogenic reflex and tubuloglomerular feedback (macula densa senses ↑ NaCl → adenosine constricts the afferent arteriole).

Clearance and its markers

The clearance equation. Clearance is the volume of plasma completely cleared of a substance per unit time (mL/min): C = (U × V) / P, where U is the urine concentration, V the urine flow rate, and P the plasma concentration. Filtered load is GFR × plasma concentration; comparing it with the amount excreted (U × V) shows whether the tubule removed or added the substance.

Inulin measures GFR. Inulin is freely filtered and neither reabsorbed nor secreted, so its clearance equals GFR (the gold standard; normal ~100–120 mL/min). Creatinine clearance is the clinical estimate but slightly overestimates GFR because a little creatinine is secreted. At steady state serum creatinine varies inversely with GFR, so halving GFR roughly doubles creatinine.

PAH measures renal plasma flow. Para-aminohippurate is filtered AND actively secreted by the proximal tubule, so nearly all of it is removed in one pass; its clearance approximates effective renal plasma flow (RPF, ~600 mL/min). Renal blood flow follows from the hematocrit, RBF = RPF / (1 − Hct), about 1 L/min or roughly 20–25% of cardiac output.

Filtration fraction. FF = GFR / RPF, normally about 20%: the fraction of plasma entering the glomerulus that is filtered. Angiotensin II raises it; ACE inhibitors lower it.

~20%Filtration fraction (GFR/RPF)

~600 mL/minEffective RPF (PAH clearance)

~100–120 mL/minNormal GFR (inulin clearance)

Reading a clearance. Compare any substance's clearance with inulin clearance (= GFR).

Clearance compared with GFR

Clearance vs GFR	Meaning	Examples
Equal	Filtered only	Inulin
Less	Net reabsorption	Glucose (~0, fully reabsorbed), Na⁺, HCO₃⁻
Greater	Net secretion	PAH (highest clearance); creatinine slightly

The filtration barrier and Starling forces

Three-layer barrier. Fenestrated capillary endothelium, the glomerular basement membrane, and the podocyte slit diaphragm (built on nephrin) restrict filtration by size and by charge. Negatively charged components such as heparan sulfate repel anionic albumin; loss of that negative charge, as in nephrotic syndrome, lets albumin through.

Starling forces. GFR = Kf × [(P_GC − P_BS) − (π_GC − π_BS)]. Glomerular capillary hydrostatic pressure (P_GC) favors filtration; Bowman space hydrostatic pressure (P_BS) and glomerular capillary oncotic pressure (π_GC) oppose it. Bowman space oncotic pressure (π_BS) is normally ~0 because protein is not filtered, and π_GC rises along the capillary as protein-free fluid leaves.

What shifts each term. Arteriolar tone sets P_GC. Ureteral obstruction raises P_BS, and a high plasma protein concentration raises π_GC; both lower GFR, while hypoproteinemia does the reverse.

Arteriolar tone, drugs, and filtration fraction

Afferent arteriole. Afferent constriction reduces both inflow and P_GC, so RPF and GFR fall together and FF stays roughly unchanged; afferent dilation raises both. Prostaglandins dilate the afferent arteriole to keep the glomerulus perfused.

Efferent arteriole. Angiotensin II constricts the efferent arteriole, backing pressure up into the glomerulus: GFR rises while RPF falls, so FF rises. This preserves GFR in low-perfusion states; very severe or prolonged constriction eventually lowers GFR too, as flow falls and π_GC climbs.

Effects on glomerular dynamics

Change	GFR	RPF	FF
Afferent constriction (NSAIDs)	↓	↓	≈
Afferent dilation (prostaglandins)	↑	↑	≈
Efferent constriction (angiotensin II)	↑	↓	↑
Efferent dilation (ACE inhibitors, ARBs)	↓	↑	↓
↑ Plasma protein	↓	≈	↓
Ureteral obstruction	↓	≈	↓
Dehydration	↓	↓↓	↑

ACE inhibitors and ARBs. Removing angiotensin II tone dilates the efferent arteriole: GFR falls, RPF rises, FF falls. In bilateral renal artery stenosis (or stenosis to a solitary kidney), GFR depended on that efferent tone, so starting the drug precipitates AKI with a rising creatinine. The same fall in intraglomerular pressure is renoprotective in diabetic nephropathy, reducing hyperfiltration injury and proteinuria.

NSAIDs. Blocking prostaglandin synthesis removes afferent dilation, so the afferent arteriole constricts and RPF and GFR fall. Healthy kidneys barely notice, but AKI follows in volume depletion, heart failure, cirrhosis, or CKD, and especially with the "triple whammy" of NSAID + ACE inhibitor + diuretic, which disables both arteriolar defenses while shrinking volume.

ACE inhibitor: efferent dilation, ↓ GFR, ↑ RPF, ↓ FF. NSAID: afferent constriction, ↓ GFR, ↓ RPF. Both hurt most when renal perfusion is already marginal.

Autoregulation

Stable GFR across pressures. RBF and GFR stay nearly constant over a MAP of ~80–180 mmHg through two mechanisms acting on the afferent arteriole. In the myogenic reflex, a rise in pressure stretches the afferent arteriole, which contracts and holds flow constant. Tubuloglomerular feedback works through the macula densa:

GFR risesMore NaCl reaches the macula densa
Macula densa senses NaClReleases adenosine
Afferent arteriole constrictsP_GC falls
GFR returns toward normalLow NaCl does the reverse and stimulates renin

Tubuloglomerular feedback

Below the autoregulatory range, GFR falls with pressure, which is why prolonged hypotension causes prerenal azotemia and, eventually, ischemic tubular injury.