Measured GFR (Iohexol or Isotope)
Measured glomerular filtration rate (mGFR) is a direct measure of how fast the kidneys filter blood. A substance that is filtered freely at the glomerulus and is not secreted, reabsorbed or made by the kidney is injected, and its clearance from the plasma, or its appearance in the urine, gives the GFR. It is the reference test for kidney function.
The usual markers are iohexol (an iodinated contrast agent that is not metabolised), and radioactive isotopes such as chromium-51 EDTA, technetium-99m DTPA, and iodine-125 iothalamate. Inulin is the historical reference marker but it is difficult to use.
A plasma clearance method is the most used: after an intravenous injection, blood samples are taken at set times, usually 2 to 4 hours and, in low GFR, up to 24 hours later, and the fall of the marker in plasma over time gives the clearance. A urinary clearance method needs a timed urine collection with bladder catheterisation, and is less often used.
The result is expressed in mL per minute, usually adjusted to a body surface area of 1.73 m², and sometimes reported without adjustment. The test takes 3 to 5 hours, and plasma clearance gives results that agree within about 5 to 10% with inulin. Estimating equations based on creatinine or cystatin C have errors of 20 to 30% in the general population, and larger in muscle disease, extremes of body size and pregnancy.
Indications.
- Precise kidney function when estimated GFR is unreliable: extremes of muscle mass or body size (amputation, cachexia, obesity, bodybuilders), liver disease, severe malnutrition, and muscle wasting diseases.
- Dosing of drugs with narrow therapeutic ranges and renal elimination, such as carboplatin and other chemotherapy, and certain antimicrobials.
- Assessment of living kidney donors, before donation.
- Monitoring of kidney function during treatment with nephrotoxic drugs.
- Staging of chronic kidney disease when the estimated value is near a decision threshold, for example, before transplantation or dialysis.
- Research studies, and children with kidney disease in selected cases.
- Disagreement between creatinine based and cystatin C-based estimates.
Not indicated in routine care, since estimating equations are adequate for most patients.
Contraindications and precautions.
- Allergy to iodinated contrast agents (for iohexol) in a patient with a previous serious reaction, though the amount used is very small and reactions are rare.
- Pregnancy and breastfeeding for radioisotope methods: the test is avoided or delayed, and iohexol is used if a test is essential.
- Gross oedema, ascites, or pleural effusions, where the marker distributes into the third space and delays clearance, so later samples are needed.
- Dehydration or recent contrast: fluids and timing are checked.
- Severe renal failure: the sampling time is extended, since clearance is slow.
- Patients who cannot give samples at the set times.
- Staff handling radioisotopes need appropriate radiation safety.
Preparation and technique.
The patient is well hydrated, and is asked to avoid heavy meat meals and strenuous exercise on the day, though they eat and drink normally. Height and weight are recorded to calculate body surface area. A cannula is placed in one arm, and a baseline blood sample may be taken.
A precisely measured dose of the marker is injected by the other arm, and the syringe is weighed or checked for the exact dose. The time of injection is noted exactly. Blood samples are taken from the opposite arm at set times, for example, at 2, 3 and 4 hours (later, up to 24 hours, in low GFR or oedema).
The laboratory measures the marker in each plasma sample, plots the fall, and calculates the clearance with a correction for the slow phase (a slow phase correction).
