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Title: Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake

Abstract

The finding of an enhanced excretion of (/sup 99m/Tc)dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of (/sup 99m/Tc)DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of (/sup 99m/Tc)DMSA in a human volunteer was 5.8%. Continuous infusion of (/sup 99m/Tc)DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of (/sup 99m/Tc)DMSA 34 +/- 4 ml/min, urinary clearance of (/sup 99m/Tc)DMSA 12 +/- 3 ml/min. The calculated filtered load of (/sup 99m/Tc)DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of (/sup 99m/Tc)DMSA.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
University Hospital, Groningen (Netherlands)
OSTI Identifier:
5601713
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Nucl. Med.; (United States); Journal Volume: 30:7
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; RADIOPHARMACEUTICALS; METABOLISM; TECHNETIUM 99; UPTAKE; UROGENITAL SYSTEM DISEASES; DIAGNOSIS; BLOOD-PLASMA CLEARANCE; ISOMERIC NUCLEI; KIDNEYS; PATIENTS; PROTEINS; RATS; RENAL CLEARANCE; SUCCINIC ACID; THIOLS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; CLEARANCE; DICARBOXYLIC ACIDS; DISEASES; DRUGS; EXCRETION; HOURS LIVING RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; ORGANS; RADIOISOTOPES; RODENTS; TECHNETIUM ISOTOPES; VERTEBRATES; YEARS LIVING RADIOISOTOPES 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics

Citation Formats

de Lange, M.J., Piers, D.A., Kosterink, J.G., van Luijk, W.H., Meijer, S., de Zeeuw, D., and van der Hem, G.K. Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake. United States: N. p., 1989. Web.
de Lange, M.J., Piers, D.A., Kosterink, J.G., van Luijk, W.H., Meijer, S., de Zeeuw, D., & van der Hem, G.K. Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake. United States.
de Lange, M.J., Piers, D.A., Kosterink, J.G., van Luijk, W.H., Meijer, S., de Zeeuw, D., and van der Hem, G.K. 1989. "Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake". United States. doi:.
@article{osti_5601713,
title = {Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake},
author = {de Lange, M.J. and Piers, D.A. and Kosterink, J.G. and van Luijk, W.H. and Meijer, S. and de Zeeuw, D. and van der Hem, G.K.},
abstractNote = {The finding of an enhanced excretion of (/sup 99m/Tc)dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of (/sup 99m/Tc)DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of (/sup 99m/Tc)DMSA in a human volunteer was 5.8%. Continuous infusion of (/sup 99m/Tc)DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of (/sup 99m/Tc)DMSA 34 +/- 4 ml/min, urinary clearance of (/sup 99m/Tc)DMSA 12 +/- 3 ml/min. The calculated filtered load of (/sup 99m/Tc)DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of (/sup 99m/Tc)DMSA.},
doi = {},
journal = {J. Nucl. Med.; (United States)},
number = ,
volume = 30:7,
place = {United States},
year = 1989,
month = 7
}
  • The relative renal uptake of Tc-99m DMSA was compared with the relative glomerular filtration rate (GFR) in ten patients with serum creatinines ranging from 0.3 to 2.5 mg/dl. Relative GFR was based on the renal uptake of Tc-99m DTPA determined by two methods: 1) integrating the counts from 1 to 3 minutes postinjection and correcting for background. 2) Totalizing the individual renal counts in a single 15-second frame from 2:45 minutes to 3:00 minutes postinjection and correcting for background. The two methods of determining relative DTPA uptake showed excellent correlation, r = 0.98. Relative DMSA uptake determined at 24 hoursmore » post-injection using computer-assisted regions of interest showed excellent correlation with the relative GFR determined by either the integral or single-frame method, r = 0.98. The addition of background subtraction for the DMSA images at 24 hours did not improve the correlation.« less
  • The renal handling of technetium-99m dimercaptosuccinic acid (99mTc DMSA) was studied in rats treated with high doses of nonradioactive DMSA to inhibit the renal uptake mechanism(s). A static scan was obtained 1 hour after the intravenous (iv) injection of 99mTc DMSA and the radioactivity in kidneys and bladder was calculated as a percentage of the injected amount. Total glomerular filtration rate (GFR) and effective renal plasma flow were also determined. Preloading with DMSA caused a fall in the renal accumulation of 99mTc DMSA together with a small increase in the amount excreted into the urinary bladder. Despite a stable GFR,more » the total amount of 99mTc DMSA handled by the kidneys (i.e., renal plus bladder activity) was reduced. These findings are compatible with the hypothesis that peritubular uptake and subsequent intracellular fixation are of importance in the renal accumulation of 99mTc DMSA. On the other hand, the radioactivity excreted into the urine probably stems from non-reabsorbed 99mTc DMSA initially filtered by the glomeruli.« less
  • Quantitative single photon emission computed tomography (SPECT) methodology based on calibration with kidney phantoms has been applied for the assessment of renal uptake of (/sup 99m/Tc)DMSA in 25 normals; 16 patients with a single normal kidney; 30 patients with unilateral nephropathy; and 17 patients with bilateral nephropathy. An excellent correlation (r = 0.99, s.e.e. = 152) was found between SPECT measured concentration and actual concentration in kidney phantoms. Kidney uptake at 6 hr after injection in normals was 20.0% +/- 4.6% for the left and 20.8% +/- 4.4% for the right. Patients with unilateral nephropathy had a statistically significant (pmore » less than 0.001) low uptake in the diseased kidney (7.0% +/- 4.7%), but the contralateral kidney uptake did not differ from the normal group (20.0% +/- 7.0%). The method was especially useful in patients with bilateral nephropathy. Significantly (p less than 0.001) decreased uptake was found in both kidneys (5.1% +/- 3.4% for the left and 6.7% +/- 4.2% for the right). The total kidney uptake (right and left) in this group showed to be inversely correlated (r = 0.83) with serum creatinine. The uptake of (/sup 99m/Tc)DMSA in single normal kidney was higher (p less than 0.001) than in a normal kidney (34.7% +/- 11.9%), however, it was lower than the total absolute uptake (RT + LT = 41.5% +/- 8.8%) in the normal group. The results indicate that SPECT is a reliable and reproducible technique to quantitate absolute kidney uptake of (/sup 99m/Tc)DMSA.« less
  • The uptake of SYMg by isolated renal tubules of winter flounder, Pseudopleuronectes americanus, was studied by compartmental analysis. Two phases of uptake were seen in steady-state conditions. The slow-exchanging compartment was 46% of the total Mg content, and uptake into this compartment was saturable and inhibited by 10 mM CaCl2, dinitrophenol, and ouabain but not by furosemide, Na-free medium, or cytochalasin B. The fast-exchanging compartment was 5% of the total Mg, and uptake into this compartment showed sigmoid saturation kinetics. The fast uptake rate was inhibited by dinitrophenol, ouabain, Na-free medium, 10 mM CaCl2, and furosemide but stimulated by cytochalasinmore » B. SYMg efflux from brush border membrane vesicles (BBMV) was stimulated by both an inside positive electrical potential generated by 100 mM KCl and by 100 mM NaCl. BBMV uptake was inhibited by 10 mM CaCl2 and unaffected by furosemide. The relationship of electrical gradient-driven and Na gradient-driven Mg transport to the Mg secretory function of these tubules is discussed.« less
  • True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- ({sup 99m}Tc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of {sup 99m}Tc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasmamore » differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-({sup 125}I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.« less