Radionuclide method for evaluating the performance of hemodialysis in vivo.
BACKGROUND
Specifications of dialyzer performance are generally based on in vitro measurements. There is, however, a shortage of data on dialyzer performance in vivo. The aim of this study was to use continuous measurement of technetium-99m-diethyltriaminepentaacetic acid (Tc-99m-DTPA) blood concentration as a means of continuously monitoring dialyzer function in vivo in patients undergoing routine hemodialysis.


METHODS
The study population comprised 15 patients (45 to 80 years old; 13 males). Tc-99m-DTPA was administered intravenously 90 minutes before obtaining a blood sample and starting dialysis. Blood Tc-99m-DTPA activity was continuously monitored by passing the line carrying blood from the patient to the dialyzer close to a scintillation probe mounted in a shielded housing. At the end of hemodialysis, lasting 180 to 300 minutes, chromium-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) was given intravenously and a blood sample taken 90 minutes later. Baseline dialyzer blood flow (Q(b)) and dialysate flow (Q(d)) were 250 to 350 mL/min and 500 mL/min, respectively. The rate constant, alpha, of the decrease in blood Tc-99m-DTPA activity was used as the measure of moment-to-moment dialyzer function. Pre- and postdialysis extracellular fluid volumes were calculated from the blood Tc-99m-DTPA and Cr-51-EDTA concentrations (V(DTPA) and V(EDTA)) before and after dialysis. Tc-99m-DTPA clearance was measured as the product of alpha and V(DTPA). Dialyzer urea clearance was calculated from pre- and postdialysis urea nitrogen concentrations and the time of dialysis. The effects of brief changes in Q(b) and Q(d) on dialyzer function were assessed from the associated changes in alpha.


RESULTS
The Tc-99m-DTPA clearance profile was biexponential, becoming monoexponential about 1 hour after starting hemodialysis, with alpha remaining constant for as long as dialysis continued in five patients in whom Q(b) and Q(d) were left unaltered. Mean (SEM) plasma Tc-99m-DTPA clearance averaged over the entire period of dialysis in all 15 patients was 110 (3.1) mL/min. It correlated with urea clearance (r= 0.71) (P < 0.01) which was 225 (9.5) mL/min based on a total body water of 2.5 that of V(DTPA) and 212 (13) mL/min scaled to 40 L/1.73 m(2). Extracellular fluid volume decreased by 1.73 (0.74) l over dialysis, which was comparable to the change in weight [1.48 (0.57) kg]. The extraction fraction of Tc-99m-DTPA across the artificial kidney, directly measured from afferent and efferent blood samples under baseline Q(b) and Q(d), was 0.5 (0.013). Average extraction fraction indirectly estimated from Tc-99m-DTPA blood clearance and Q(b) was 0.54 (0.019). These two measurements of extraction fraction correlated with each other under conditions of varying Q(b) and Q(d) (r= 0.74) (N= 27) (P < 0.001). Changes in alpha resulting from changes in Q(b) and Q(d) were similar to changes predicted from computerized modeling. The ratio of mass transfer coefficients of urea and Tc-99m-DTPA with respect to the dialyzer, calculated as if they were permeability-surface area products, was 3.3, similar to the ratio, obtained from the literature, in continuous capillary endothelium.


CONCLUSIONS
Tc-99m-DTPA is a useful agent for continuously monitoring dialyzer function in vivo and provides a platform for the use of other radio-pharmaceuticals of different molecular sizes that could be used in an analogous fashion.
Bihl
Geoffrey R
GR
Hemodialysis Unit and Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
Bird
Nicholas J
NJ
Peters
Christina
C
Bradley
John R
JR
Peters
A Michael
AM
D000368:Aged; D000369:Aged, 80 and over; D002860:Chromium Radioisotopes; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D014462:Ultrafiltration; D014508:Urea / Q000378:metabolism
D002860:Chromium Radioisotopes; D014508:Urea; D016284:Technetium Tc 99m Pentetate