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GFR Analysis
Paige Bennett, MD
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KEY FACTS

  • Terminology

    • Radiopharmaceuticals 

      TERMINOLOGY

      • Definitions

        • Glomerular filtration rate (GFR) analysis
          • Commonly performed in patients considering kidney donation for transplant
          • More accurate than estimated GFR
          • GFR: Plasma volume presented to nephrons per unit time (mL/min)
          • Normal GFR: Young adults ~ 120 mL/min/1.73 m², decreases normally with age
      • Nuclear Medicine GFR Analysis 

        • Radionuclide administered IV to patient 
        • Counts obtained on plasma samples over time counted in gamma counter and compared to standard sample
        • Utilizes radionuclides that are cleared by glomerular filtration 
        • Use same clock for entire procedure day 
        • Ideal characteristics of GFR analysis radiopharmaceutical
          • Only glomerular filtration, where plasma = urinary clearance
          • Low molecular weight and small molecular size allows free glomerular membrane filtration
          • Inert otherwise: No protein binding, no cellular metabolism, no traveling across cells, not renal toxic, no excretion besides by kidneys, no tubular excretion/absorption
          • Inulin is gold standard for GFR measurement; not used because expensive, time-consuming, technically difficult: Multiple urine samples required; difficult in people with urologic disease, children
          • Needs to not dissociate from radioactive moiety
        • Usually lab-based procedure but can also be performed through gamma camera imaging
      • Lab Procedure 

        • Confirm patient has not had another nuclear medicine study or therapy recently (confirm 4 half-lives since study/therapy)
        • Reliable for patients > 3 months old; however, may be spurious in patients up until ~ 2 years due to continual maturation of renal parenchyma from 0-2 years 
        • Tracer preparation
          • Patient dose and standard dose drawn from radiopharmacy supply (2 doses total needed)
          • Record
            • Quantity of patient dose and standard dose (volume, activity or weight)
            • Time of measurement 
            • Patient weight 
          • Radiopharmaceuticals 
            • Tc-99m diethylenetriaminepentaacetic acid (DTPA): Confirm purity (> 98%), may dissociate 
              • Adult dose: 2-10 mCi (74-370 MBq); higher end used if imaging in addition to GFR analysis 
              • Pediatric dose: 1 mCi (37 MBq) max 
              • t1/2: 6 hours (count samples within 24 hours of blood draw)
            • Cr-51 ethylenediamine tetraacetic acid (EDTA): Tight binding, minimal dissociation 
              • Adult dose: 80 uCi (3 MBq)
              • Pediatric dose: 80 uCi (3 MBq) max
              • Not available in United States 
              • t1/2: 27.7 days (can count samples at later time due to long t1/2; waste storage requires long time)
            • Reliable for GFR > 30 mL/min
        • Administration
          • Administer patient dose IV
            • Confirm no extravasation using gamma camera
            • If extravasation, study is not valid and needs to be repeated
            • Flush with normal saline 
          • Record
            • Time of administration 
            • Residual volume, activity or weight of administration syringe
        • Sample
          • Obtain venous blood sample on limb opposite that of administration (10 mL in adults, 7 mL in children)
            • 2 samples at 2-hour interval: 1 and 3 hours or 2 and 4 hours
              • Record time samples obtained 
            • Isolate plasma through centrifugation of sample
            • Prepare ~ 1 mL plasma (two 1-mL samples can be prepared for each time point; helps to detect errors)
          • Standard sample drawn from standard solution then diluted 
            • Prepare ~ 1 mL standard (two 1-mL samples can be prepared; helps to detect errors)
          • Background sample 
            • Prepare ~ 1 mL water 
        • Counting
          • Standard, background, plasma
          • Count each sample for > 10K counts 
            • May dilute samples to avoid dead-time errors; dilute all samples similarly
          • Apply decay correction for plasma and standard samples 
          • Usually use well counter, but counts can also be obtained with gamma camera
          • Each sample should be counted twice
        • GFR calculation 
          • To reduce errors, check input count values, calculations, times, as well as agreement between 2 samples of same type at same time
          • 2-sample method (slope-intercept)
            • Clearance is expressed as injected dose divided by area under plasma curve
          • Normalize to 1.73 m² using formula: BSA (cm) = [wt (kg)] ⁰·⁴²⁵ x [ht (cm)] ⁰·⁷²⁵ x 71.84

      Selected References

      1. Bibbo G et al: Comparison of glomerular filtration rates determined using two- and single-blood sample methods with a three-blood sample technique for 2922 paediatric studies. Nucl Med Commun. 40(12):1204-10, 2019
      2. McMeekin H et al: 99mTc DTPA vs. 51Cr EDTA for glomerular filtration rate measurement: is there a systematic difference? Nucl Med Commun. 40(12):1224-9, 2019
      3. Lam NN et al: Renal and cardiac assessment of living kidney donor candidates. Nat Rev Nephrol. 13(7):420-8, 2017
      4. Murray AW et al: Assessment of glomerular filtration rate measurement with plasma sampling: a technical review. J Nucl Med Technol. 41(2):67-75, 2013
      Related Anatomy
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      References
      Tables

      Tables

      KEY FACTS

      • Terminology

        • Radiopharmaceuticals 

          TERMINOLOGY

          • Definitions

            • Glomerular filtration rate (GFR) analysis
              • Commonly performed in patients considering kidney donation for transplant
              • More accurate than estimated GFR
              • GFR: Plasma volume presented to nephrons per unit time (mL/min)
              • Normal GFR: Young adults ~ 120 mL/min/1.73 m², decreases normally with age
          • Nuclear Medicine GFR Analysis 

            • Radionuclide administered IV to patient 
            • Counts obtained on plasma samples over time counted in gamma counter and compared to standard sample
            • Utilizes radionuclides that are cleared by glomerular filtration 
            • Use same clock for entire procedure day 
            • Ideal characteristics of GFR analysis radiopharmaceutical
              • Only glomerular filtration, where plasma = urinary clearance
              • Low molecular weight and small molecular size allows free glomerular membrane filtration
              • Inert otherwise: No protein binding, no cellular metabolism, no traveling across cells, not renal toxic, no excretion besides by kidneys, no tubular excretion/absorption
              • Inulin is gold standard for GFR measurement; not used because expensive, time-consuming, technically difficult: Multiple urine samples required; difficult in people with urologic disease, children
              • Needs to not dissociate from radioactive moiety
            • Usually lab-based procedure but can also be performed through gamma camera imaging
          • Lab Procedure 

            • Confirm patient has not had another nuclear medicine study or therapy recently (confirm 4 half-lives since study/therapy)
            • Reliable for patients > 3 months old; however, may be spurious in patients up until ~ 2 years due to continual maturation of renal parenchyma from 0-2 years 
            • Tracer preparation
              • Patient dose and standard dose drawn from radiopharmacy supply (2 doses total needed)
              • Record
                • Quantity of patient dose and standard dose (volume, activity or weight)
                • Time of measurement 
                • Patient weight 
              • Radiopharmaceuticals 
                • Tc-99m diethylenetriaminepentaacetic acid (DTPA): Confirm purity (> 98%), may dissociate 
                  • Adult dose: 2-10 mCi (74-370 MBq); higher end used if imaging in addition to GFR analysis 
                  • Pediatric dose: 1 mCi (37 MBq) max 
                  • t1/2: 6 hours (count samples within 24 hours of blood draw)
                • Cr-51 ethylenediamine tetraacetic acid (EDTA): Tight binding, minimal dissociation 
                  • Adult dose: 80 uCi (3 MBq)
                  • Pediatric dose: 80 uCi (3 MBq) max
                  • Not available in United States 
                  • t1/2: 27.7 days (can count samples at later time due to long t1/2; waste storage requires long time)
                • Reliable for GFR > 30 mL/min
            • Administration
              • Administer patient dose IV
                • Confirm no extravasation using gamma camera
                • If extravasation, study is not valid and needs to be repeated
                • Flush with normal saline 
              • Record
                • Time of administration 
                • Residual volume, activity or weight of administration syringe
            • Sample
              • Obtain venous blood sample on limb opposite that of administration (10 mL in adults, 7 mL in children)
                • 2 samples at 2-hour interval: 1 and 3 hours or 2 and 4 hours
                  • Record time samples obtained 
                • Isolate plasma through centrifugation of sample
                • Prepare ~ 1 mL plasma (two 1-mL samples can be prepared for each time point; helps to detect errors)
              • Standard sample drawn from standard solution then diluted 
                • Prepare ~ 1 mL standard (two 1-mL samples can be prepared; helps to detect errors)
              • Background sample 
                • Prepare ~ 1 mL water 
            • Counting
              • Standard, background, plasma
              • Count each sample for > 10K counts 
                • May dilute samples to avoid dead-time errors; dilute all samples similarly
              • Apply decay correction for plasma and standard samples 
              • Usually use well counter, but counts can also be obtained with gamma camera
              • Each sample should be counted twice
            • GFR calculation 
              • To reduce errors, check input count values, calculations, times, as well as agreement between 2 samples of same type at same time
              • 2-sample method (slope-intercept)
                • Clearance is expressed as injected dose divided by area under plasma curve
              • Normalize to 1.73 m² using formula: BSA (cm) = [wt (kg)] ⁰·⁴²⁵ x [ht (cm)] ⁰·⁷²⁵ x 71.84

          Selected References

          1. Bibbo G et al: Comparison of glomerular filtration rates determined using two- and single-blood sample methods with a three-blood sample technique for 2922 paediatric studies. Nucl Med Commun. 40(12):1204-10, 2019
          2. McMeekin H et al: 99mTc DTPA vs. 51Cr EDTA for glomerular filtration rate measurement: is there a systematic difference? Nucl Med Commun. 40(12):1224-9, 2019
          3. Lam NN et al: Renal and cardiac assessment of living kidney donor candidates. Nat Rev Nephrol. 13(7):420-8, 2017
          4. Murray AW et al: Assessment of glomerular filtration rate measurement with plasma sampling: a technical review. J Nucl Med Technol. 41(2):67-75, 2013