Evaluation of Kidney Function in Children With Brain Tumors

Background

Children with brain tumors are often treated with chemotherapeutic regimes that include
methotrexate or cisplatinium. Both these drugs are nephrotoxic and may cause damage to the
kidneys. To identify renal damage that occurs as a result of this drug therapy, renal
function is evaluated at 3 or 6 month intervals during treatment. Renal function is
traditionally measured by estimating glomerular filtration rate (GFR) using nuclear
scintigraphy or collection of 24 hours of urine to measure creatinine clearance.
Unfortunately these tests are tedious, require meticulous techniques and can be unreliable.
In addition, a separate visit to the hospital is required to perform these tests. Children
with brain tumors undergoing these regimes routinely have contrast-enhanced MRI of the
brain performed at 3 month intervals in order to evaluate tumor response.

Recently, new and innovative MR urography techniques have been used to measure renal
function. By calculating the transfer of a contrast agent (gadolinium-DTPA) from the
vascular space to the glomerular space, under certain assumptions, the GFR can be
calculated. We have modified this technique – called the Patlak plot – to generate a
numeric value in mls/min that is thought to be directly proportional to the GFR for each
kidney. We have called this value the “Patlak Number”. The relationship of this “Patlak
Number” to GFR is determined by the patient’s hematocrit, body surface area and an as yet
undetermined constant related to the relaxivity of gadolinium-DTPA.

After routine non-contrast imaging of the brain is performed, we will perform functional
evaluation of the kidneys immediately after contrast administration. After the kidneys are
evaluated, routine post-contrast imaging of the brain will be performed. To calculate the
Patlak plot we require dynamic imaging of the kidneys from the time of aortic enhancement up
to the point when contrast is excreted by the kidney and appears in the collecting system.
From our previous studies on renal transit time, we know that contrast is excreted in less
than four minutes in non-obstructed kidneys. Therefore the dynamic renal imaging should be
accomplished in five minutes. In order for the studies to be reproducible a power injector
will be used for all studies, including those on patients with ports. The maximum flow rate
for the injection will be 1 ml/sec. As opposed to our dedicated renal studies, hydration and
diuretic administration would not be required. We would need to move the table such that the
kidneys are at the centre of the magnet and acquire scout images prior to injecting the
contrast and the table will need to be moved back prior to imaging the brain so the
procedure will add a maximum of 10 minutes to the total imaging procedure. The brain imaging
will commence approximately 5 minutes after the injection of contrast. Since we currently do
not perform any dynamic imaging of the initial, vascular phase of the contrast for these
tumor patients this delay will not interfere in evaluation of the brain tumor. In fact when
using a standard dose of contrast delayed imaging has been shown to be more effective (than
imaging immediately after contrast) in the detection of small tumors (Yuh WTC et al. AJNR
1995;16:373-380) so the 5 minute delay prior to commencing imaging should, if anything,
improve the efficacy of the tumor evaluation.

We hope to show that MR urography can be used to non-invasively and objectively quantitate
renal function both globally and with respect to each individual kidney. This technique has
wide-ranging applications in children with disorders of the urinary tract as well as those
who are subjected to potentially nephrotoxic agents. It will be especially helpful in the
evaluation of children with bilateral renal disease for whom we currently have limited
ability to monitor disease progression or treatment response.

If normal values can be established, this technique could potentially become the standard to
evaluate renal function in children. By combining this functional evaluation with anatomic
evaluation of the urinary tract we can comprehensively evaluate the kidneys and urinary
tract in a single test that does not use ionizing radiation.

Purpose:

Our purpose is to evaluate renal function at the same time the child’s brain tumor is being
evaluated. We will calculate the “Patlak Number” at the same time that the routine brain
scan is performed. In those children who are having GFR calculated by traditional methods,
we would compare these GFR values to the “Patlak Number”. In the other children with brain
tumors who are not receiving nephrotoxic drugs and who have normal renal function, we will
calculate the “Patlak Number” to establish normal values at different ages – children with
impaired renal function will be excluded from this group.

Patient selection

All children currently enrolled, and who will be enrolled during the course of the study, in
the chemotheraphy program at CHOA at Scottish Rite will be given the opportunity to
participate in the study. All such children will receive multiple MRI exams to monitor the
progress of the chemotherapy and the MRI exams will include an injection of contrast. There
are no ineligabilty criteria.

Pre-treatment evaluation

There is no extra pre-treatment evaluation over and above that done for the chemotherapy.

Registration/radomisation

All patients presenting for chemotherapy will be offered the opportunity to participate.

Therapy

The results from the renal MRI study will be compared with the value provided by the lab
test method routinely used to evaluate the renal function of these children.

Pathology

No central review is required as the pathology (the tumour) is the not the object of this
study.

Patient assessment

Every patient presenting at the tumour clinic will be given the chance to participate in the
study.

Data collection

Informed consent Tumour clinic MRI renal data Next scheduled MRI Creatanine clearance
result The lab test closest in time to the MRI exam.

Statistical considerations

The desired patient population of 50 should be adequate to establish if the MRI value of GFR
is linearly correlated with the creatine clearance results.

Inclusion Criteria:

- All children currently enrolled, and who will be enrolled during the course of the
study, in the chemotheraphy program at Children's Healthcare of Atlanta at Scottish
Rite

Exclusion Criteria:

-