Renal ultrafiltration changes induced by focused US.
OBJECTIVE
To determine if focused ultrasonography (US) combined with a diagnostic microbubble-based US contrast agent can be used to modulate glomerular ultrafiltration and size selectivity.


METHODS
The experiments were approved by the animal care committee. The left kidney of 17 healthy rabbits was sonicated by using a 260-kHz focused US transducer in the presence of a microbubble-based US contrast agent. The right kidney served as the control. Three acoustic power levels were applied: 0.4 W (six rabbits), 0.9 W (six rabbits), and 1.7 W (five rabbits). Three rabbits were not treated with focused US and served as control animals. The authors evaluated changes in glomerular size selectivity by measuring the clearance rates of 3000- and 70,000-Da fluorescence-neutral dextrans. The creatinine clearance was calculated for estimation of the glomerular filtration rate. The urinary protein-creatinine ratio was monitored during the experiments. The authors assessed tubular function by evaluating the fractional sodium excretion, tubular reabsorption of phosphate, and gamma-glutamyltransferase-creatinine ratio. Whole-kidney histologic analysis was performed. For each measurement, the values obtained before and after sonication were compared by using the paired t test.


RESULTS
Significant (P < .05) increases in the relative (ratio of treated kidney value/nontreated kidney value) clearance of small- and large-molecule agents and the urine flow rates that resulted from the focused US treatments were observed. Overall, 1.23-, 1.23-, 1.61-, and 1.47-fold enhancement of creatinine clearance, 3000-Da dextran clearance, 70 000-Da dextran clearance, and urine flow rate, respectively, were observed. Focal tubular hemorrhage and transient functional tubular alterations were observed at only the highest (1.7-W) acoustic power level tested.


CONCLUSIONS
Glomerular ultrafiltration and size selectivity can be temporarily modified with simultaneous application of US and microbubbles. This method could offer new opportunities for treatment of renal disease.
Fischer
Krisztina
K
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Focused Ultrasound Laboratory, 221 Longwood Ave, Room 515, Boston, MA 02215, USA. kfischer@bwh.harvard.edu
McDannold
Nathan J
NJ
Zhang
Yongzhi
Y
Kardos
Magdolna
M
Szabo
Andras
A
Szabo
Antal
A
Reusz
Gyorgy S
GS
Jolesz
Ferenc A
FA
D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000652:urine; D003911:Dextrans / Q000652:urine; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000528:radiation effects*; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D045423:Microbubbles; D011817:Rabbits; D018709:Statistics, Nonparametric; D014465:Ultrasonics; D014554:Urination
D003287:Contrast Media; D003911:Dextrans; D005466:Fluorocarbons; D003404:Creatinine; C042852:perflutren
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