Physiology chapters
Renal clearance
What clearance means and how it is calculated, why inulin and creatinine measure GFR, how PAH measures renal plasma flow, the clearance of glucose, urea and sodium, and free water clearance.
- Clearance is the volume of plasma completely cleared of a substance per minute: C = (U × V) ÷ P.
- Inulin is filtered and neither reabsorbed nor secreted, so its clearance equals GFR (about 125 mL/min); creatinine is the practical bedside marker.
- PAH is filtered and almost completely secreted, so its clearance measures renal plasma flow (about 650 mL/min); glucose clearance is normally zero until the transport maximum is exceeded.
On this page
Overview
Clearance tells us how efficiently the kidneys remove a substance from plasma. It is the volume of plasma that would be completely cleared of the substance each minute.
Clearance is used to measure GFR and renal plasma flow, and to understand how the kidney handles each substance.
The clearance formula
C = (U × V) ÷ P
- C: clearance (mL/min).
- U: concentration in urine.
- V: urine flow rate (mL/min).
- P: concentration in plasma.
Example: urine inulin 100 mg/mL, urine flow 1.25 mL/min, plasma inulin 1 mg/mL. Clearance = (100 × 1.25) ÷ 1 = 125 mL/min.
Comparing clearance with GFR
| Clearance compared with GFR | Meaning | Example |
|---|---|---|
| Equal | Filtered only; not reabsorbed or secreted | Inulin |
| Less than GFR | Net reabsorption | Glucose, amino acids, sodium, urea |
| Greater than GFR | Net secretion | PAH, many drugs, creatinine (slightly) |
If a substance's clearance is higher than inulin clearance, it must be secreted by the tubules.
Inulin: the gold standard for GFR
Inulin (a plant polysaccharide) is ideal because it is:
- Freely filtered.
- Not reabsorbed and not secreted.
- Not made, broken down or stored by the kidney.
- Not toxic, and easy to measure.
So inulin clearance = GFR (about 125 mL/min). It needs a continuous infusion, so it is used mainly in research.
Creatinine
Creatinine comes from muscle creatine at a fairly steady rate.
- It is filtered freely and slightly secreted, so creatinine clearance slightly overestimates GFR (by about 10–20%).
- It is convenient: no infusion is needed; a 24-hour urine collection and a blood sample are enough.
- In practice, estimated GFR (eGFR) is calculated from plasma creatinine, age and sex.
Plasma creatinine rises as GFR falls, but not in a straight line: GFR must fall by about half before plasma creatinine clearly rises above normal. Creatinine also depends on muscle mass.
A "normal" creatinine in a small, elderly woman with low muscle mass can hide a low GFR.
PAH: measuring renal plasma flow
Para-aminohippuric acid (PAH) is filtered and then almost completely secreted by the proximal tubule in one pass (about 90%). Nearly all PAH entering the kidney leaves in the urine.
So PAH clearance ≈ effective renal plasma flow (ERPF), about 650 mL/min.
- Renal blood flow = renal plasma flow ÷ (1 − haematocrit). With a haematocrit of 0.45: about 650 ÷ 0.55 ≈ 1,200 mL/min.
- Filtration fraction = GFR ÷ RPF = 125 ÷ 650 ≈ 0.2.
Inulin clearance = GFR. PAH clearance = renal plasma flow.
Glucose
Glucose is filtered and normally completely reabsorbed in the proximal tubule by sodium-glucose cotransporters (SGLT2 mainly, SGLT1). So normal glucose clearance is zero.
The transporters can carry only so much: the transport maximum (Tm) for glucose is about 375 mg/min.
- The renal threshold is the plasma glucose at which glucose first appears in the urine: about 180–200 mg/dL (about 10–11 mmol/L).
- The threshold is reached before the full Tm because nephrons differ in their capacity (splay).
Glucose appears in urine (glycosuria) when plasma glucose exceeds about 180–200 mg/dL, as in uncontrolled diabetes. SGLT2 inhibitor drugs (such as empagliflozin) lower blood glucose by causing glycosuria.
Renal glycosuria (an inherited low threshold) and pregnancy (higher GFR, lower threshold) can cause glucose in urine with normal blood glucose.
Urea
Urea is filtered and about 40–50% reabsorbed, so its clearance is about half of GFR.
Urea reabsorption increases when urine flow is low (dehydration), because water reabsorption concentrates urea in the tubule. So blood urea rises more than creatinine in dehydration.
Urea also helps the kidney concentrate urine: it is recycled in the inner medulla, adding to the medullary osmotic gradient (see tubular transport).
Sodium
About 99% of filtered sodium is reabsorbed, so sodium clearance is very small (about 1 mL/min or less). The fractional excretion of sodium (FENa) is normally under 1%.
FENa helps tell pre-renal kidney injury (low FENa, kidney holding on to sodium) from intrinsic tubular injury (higher FENa).
Free water clearance
Free water clearance shows whether the kidney is excreting water without solute (dilute urine) or keeping water (concentrated urine).
Free water clearance = urine flow − osmolar clearance (Cosm = Uosm × V ÷ Posm).
| Value | Urine | Situation |
|---|---|---|
| Positive | Dilute (hypotonic) | Low ADH: drinking a lot of water, diabetes insipidus |
| Zero | Isotonic | Loop diuretics (no gradient) |
| Negative | Concentrated (hypertonic) | High ADH: dehydration, SIADH |
ADH makes free water clearance negative (water is kept). No ADH makes it positive (water is lost).
Expect: the clearance formula and simple calculations, why inulin measures GFR, why creatinine overestimates it and how plasma creatinine relates to GFR, PAH and renal plasma flow, glucose Tm and renal threshold, urea handling in dehydration, and the meaning of positive and negative free water clearance.
Quick revision
- C = U × V ÷ P.
- Inulin clearance = GFR (125 mL/min). Creatinine: slight overestimate.
- PAH clearance = renal plasma flow (650 mL/min).
- Clearance > GFR: secretion. < GFR: reabsorption.
- Glucose: clearance 0; renal threshold 180–200 mg/dL; Tm about 375 mg/min.
- Urea: about half reabsorbed; more in dehydration.
- Free water clearance: positive in diabetes insipidus, negative with ADH.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What is renal clearance?
The volume of plasma completely cleared of a substance by the kidneys per minute, calculated as urine concentration × urine flow ÷ plasma concentration.
Why is inulin clearance equal to GFR?
Inulin is freely filtered and is neither reabsorbed nor secreted, so all of it in the filtrate appears in the urine.
What does PAH clearance measure?
Effective renal plasma flow, because PAH is almost completely removed from plasma in one pass through the kidney.
What is the renal threshold for glucose?
The plasma glucose at which glucose first appears in urine, about 180–200 mg/dL.