Susanne Tewes1, Marcel Gutberlet1, Van Dai Vo Chieu1, Dagmar Hartung1, Sebastian Rauhut2, Matti Peperhove1, Frank Wacker1, Faikah Gueler2, and Katja Hueper1
1Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, 2Clinic for Nephrology, Hannover Medical School, Hannover, Germany
Synopsis
Diclofenac is a nonsteroidal
anti-inflammatory drug that is frequently prescribed to reduce inflammation and
pain. It reduces the prostaglandin-synthesis and may consequently have an
effect on renal perfusion. We investigated whether arterial spin labeling can detect
reduction of renal perfusion after oral and topical application of diclofenac
compared to baseline measurements. Ten healthy subjects underwent functional MRI
of the kidney. After oral application of diclofenac renal perfusion was reduced
compared to baseline measurements (321±13
vs. 345±16 ml/(min*100g), p<0.01). No significant changes were found after
topical application. In conclusion, ASL can detect discreet changes of renal
perfusion that occur after application of diclofenac.Purpose
Diclofenac is a nonsteroidal anti-inflammatory
drug that is frequently prescribed in order to reduce inflammation and pain. It
is a non-selective inhibitor of the enzyme cyclooxygenase (COX), resulting in a
reduction of prostaglandin-synthesis and may consequently reduce renal perfusion.
Therefore, it is potentially harmful in patients at risk for renal function
impairment. Diclofenac is available for oral and topical application and has
been reported to reach measurable plasma concentration after repeated topical
application(1). With contrast-enhanced ultrasound (CEUS) a discreet
decrease of renal perfusion within one hour after oral diclofenac application could
be detected in healthy subjects(2), while no changes in para-aminohippuric
acid (PAH)-clearance, the clinical standard to measure renal blood flow over a
period of 24 hours, was found(3). Arterial spin labeling (ASL) is a
robust method for accurate quantification of renal perfusion and results are non-dependent
on the investigator. The purpose of this study was to evaluate whether systemic
or topical application of diclofenac is associated with renal perfusion
impairment in healthy subjects measured by ASL.
Material and Methods
Ten healthy subjects were
examined on three different days within a period of two weeks: 1) baseline examination
without any medication, 2) 60-100 minutes after oral application of 50 mg
diclofenac-sodium (Voltaren)(4), 3) after topical application of
diclofenac (Voltaren Emulgel Gel, 1,16%) over 4 days (three applications per
day) on an area of 21 x 27cm. Blood pressure, serum creatinine and diclofenac blood levels were
measured at each time point. MRI was performed on a 1.5 Tesla scanner (Avanto,
Siemens, Germany) and renal perfusion was measured by using a flow alternating inversion recovery (FAIR) trueFISP
ASL sequence as described previously(5). Alternating, after
slice-selective and global inversion, images were acquired in free breathing in
the coronal plane with the following parameters: TR/TE 4.0/2.0 ms, inversion
time = 1200 ms, FOV 420x420 mm, slice thickness 5 mm, repetitions 30. Following
motion correction of ASL images with elastic registration, maps of renal
perfusion were calculated. ROIs were placed in the upper, middle
and lower third of the kidneys and mean perfusion values were calculated. Paired
t-tests were used for statistical analysis. Values are given as mean±SEM.
Results
Out of
10 healthy subject, 3 were male, 7 were female. Mean age was 30±2 years (22-49
years), mean body weight 65±4 kg (53-80 kg), mean height 73±3 cm (160-188 cm). Mean blood pressure was 111±4/78±3
mmHg. Representative perfusion maps at baseline and after oral and topical
application of diclofenac are shown in figure 1. After oral application of
diclofenac, renal perfusion significantly decreased compared to baseline conditions
(321±13 vs. 345±16 ml/(min*100g), p<0.01, figure 2). No significant changes
were found after topical application compared to baseline (346±20 ml/(min*100g),
p=0.4, ns, figure 2).
Conclusion
ASL can detect discreet changes in
renal perfusion that occur after single oral application of 50 mg diclofenac in
healthy subjects. No significant changes in renal perfusion were detected after
topical application of diclofenac. The fact that diclofenac induced measurable
changes in renal perfusion even in healthy subjects should be considered in
therapy plans of patients with pre-existing renal function impairment.
ASL being able to detect discreet changes in renal perfusion could be useful
for further studies on nephrotoxic side effects of novel medication or
nephroprotective effects of novel treatment strategies in clinical studies
since it is a non-invasive, robust and quantitative technique.
Acknowledgements
No acknowledgement found.References
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