Clearance Methods (EDTA)

7.9.1 Radiopharmaceutical

• [⁵¹Cr]Cr-ethylenediamine tetraacetic acid, also known as
  • chromium-51 edetate
  • [⁵¹Cr]Cr-EDTA

7.9.2 Uptake mechanism / biology of the tracer

[⁵¹Cr]Cr-EDTA is a non-imaging radiopharmaceutical used to measure the glomerular filtration rate (GFR) through plasma sample techniques.

The gold standard for the measurement of GFR is inulin, an inert fructose polysaccharide which is freely filtered at the glomerulus and is neither reabsorbed nor secreted by the renal tubules or an extrarenal route. Nevertheless, its usefulness for the measurement of GFR has been reduced due mainly to its high cost, and because it is a time-consuming and complex technique requiring constant infusion, bladder catheterization, and significant blood sample volume [125,126]. [⁵¹Cr]Cr-EDTA has a biochemical behaviour similar to inulin, a clearance ratio ranging from 0.85 to 1.01, and offers a more economical and practical alternative for the measurement of GFR. The binding of [⁵¹Cr]Cr-EDTA to plasma proteins is less than 0.5%, and less than 1% has been found dissociated in vivo [127]. It was approved by the European Medicines Agency in 1975.

7.9.3 Indications

The serum creatinine concentration is not very sensitive to mild kidney impairment. The level of GFR is the best marker of the functional status of the kidney, and thus, its measurement may be useful in the following situations:

• To monitor nephrotoxicity associated with drugs;
• To calculate dose in chemotherapy;
• To detect renal failure when:
  • Accuracy is needed in conditions in which missing a decline in renal function can be misleading, such as single kidney, renovascular disease or renal transplant,
  • A 24 h clearance measurement, for estimation of GFR, is difficult to be performed;
• To assess potential live donors for kidney transplantation;
• To evaluate and perform the follow-up of renal function in chronic glomerulonephropathies, e.g. haemolytic uremic syndrome and diabetes mellitus;
• To define the need for dialysis or transplantation;
• To determine single kidney absolute function, in conjunction with relative renal function measurement from static or dynamic kidney scintigraphy;
• For clinical research, in studies which have the GFR as primary outcome.

7.9.4 Contra-indications

The plasma sample techniques for calculation of GFR should not be performed in the following situations:

• Patients receiving hyperhydration therapy with intravenous fluids;
• Presence of ascites, oedema, or other expanded body space;
• Expected GFR < 30mL/min.
• In these two latter conditions, urine collection techniques are generally recommended [114,128].
• It is not recommended to interrupt breast feeding [3].

7.9.5 Clinical performances

The use of [⁵¹Cr]Cr-EDTA for the calculation of GFR was validated almost 50 years ago [129].

7.9.6 Activities to administer

The suggested activities to administer are

• ⁵¹Cr-EDTA: 0.074 MBq / kg with a maximum of 3.7 MBq (children)

7.9.7 Dosimetry

The effective dose for [⁵¹Cr]Cr-EDTA is 20 µSv/MBq in patients with normal renal function and the ED is 47 µSv/MBq in patients with abnormal renal function [3]. The organ with the highest absorbed dose is the urinary bladder: 24 µGy/MBq

The effective dose for [⁵¹Cr]Cr-EDTA is: 0.74-1.7 mSv per procedure.

Caveat:
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

7.9.8 Interpretation criteria/major pitfalls

In terms of clinical report, the following data should be included: the date of the study, the patient GFR (in mL/min), the GFR corrected for body surface area (mL/min/1.73m2), and the reference range appropriate for the patient’s age.

If the measurement of GFR with [⁵¹Cr]Cr-EDTA is carried out simultaneously with the administration of technetium-99m radiopharmaceuticals for scintigraphic studies, e.g.[^99mTc]Tc-MAG3 or [^99mTc]Tc-DMSA, samples should be left to decay for 48 h before counting. In case a dynamic study with [^99mTc]Tc-MAG3 is performed on the same day and administration of furosemide is anticipated, then [⁵¹Cr]Cr-EDTA should not be administered simultaneously, but preferably before, and the tests performed sequentially, since there is a possibility that the diuretic influences the value of the GFR.

The following main precautions should be taken:

• For the administration of the activity, a central or peripheral line, or a winged needle infusion set should be used, to assure injection into the blood stream and avoid extravasation;
• Blood sampling should not be taken from the site of injection, and preferably from the contralateral arm, to avoid contamination with the administered activity;
• All patient medications should be registered, since some drugs may affect renal function. Of course, if the medication is regular and routine, the GFR measurement will reflect the true condition of the patient.

7.9.9 Patient preparation

Regarding patient preparation before the measurement of GFR with [⁵¹Cr]Cr-EDTA, special attention should be regarding the following:

• No specific hydration is necessary, but it is recommended a steady intake of fluids over the duration of the study;
• Caffeine ingestion (including tea, coffee and coke) should be avoided after 10 pm the night before the test due to their diuretic effect;
• High protein meals should be avoided before and during the study, since a protein load could increase GFR;
• Some restriction of physical activity should be kept, since exercise has a variable effect in GFR.

The GFR investigation uses very low levels of activity, and it is not necessary to interrupt breast feeding after administration of [⁵¹Cr]Cr-EDTA for this purpose [2].  Nevertheless, previous to initiating the examination, the presence of pregnancy and breast-feeding should be questioned, and the benefit-risk balance should be evaluated.

7.9.10 Methods

The “slope-intercept method using 2 to 4 blood samples, or the single-sample method can be used to measure GFR with [⁵¹Cr]Cr-EDTA [114,130,131].

Detailed recommendations regarding the paediatric procedures are available in the https://eanm.org/publications/guidelines/overview/paediatric/ [131].