Time to Excretion of Contrast, a Maastricht Prospective Observational Study

Intravascular iodinated contrast administration has become crucial to modern
medicine. Currently it is estimated that over 250 million injections are given
each year worldwide during medical scans and interventions. Risk of
contrast-induced kidney injury is expected to be strongly correlated with
exposure time. Studies on the excretion of iodinated contrast material are few
and have mostly been carried out in patients with normal renal function. It is
therefore not known how long contrast is retained before excretion in patients
with reduced renal function: some papers state most of the administered
contrast is eliminated within 1 to 2 hours post-contrast, others include case
wise reports of renograms persisting for many days post-contrast. Chronically
reduced renal function is expected to be a factor in delayed contrast
elimination, but it is not known which patients are most susceptible or to what
extent.

Reduced renal function is expected to increase the delay in contrast
elimination. Delayed contrast elimination is hypothesised in turn to increase
contrast toxicity, which is expected to increase the risk of post-contrast
adverse events. Patients with eGFR <30 mL/min/1.73m2 are most at risk of renal
injury after intravascular iodinated contrast material injection; patients with
eGFR 30-59 mL/min/1.73m2 are considered at moderate to ow risk, and patients
with eGFR >=60 mL/min/1.73m2 are considered to be at low to no risk. Whereas
such contrast administration appears to be safe for the majority of patients
even with eGFR <30 mL/min/1.73m2, reports of individuals with post-contrast
adverse events persist. It may be that the distinguishing characteristic is
contrast retention.

A second issue pertaining to iodinated contrast elimination is gaining more and
more attention: contrast-pollution in water. Currently pilots are being carried
out in which patients are asked to collect all urine during 24-hours and to
subsequently dispose the urine containers as a waste product. Whether this
24-hour collection is necessary has not been determined.

The aim of the current study is to determine contrast elimination time and %
contrast eliminated within 5 days in three groups of patients, (with severely
reduced, moderate, and mildly reduced to normal renal function). Secondary aims
are to explore whether specific situations/characteristics result in higher
probability of delayed elimination of contrast, and whether there is a link
between elimination time and adverse post-contrast outcomes.

Relevant characteristics of patients and procedures will be recorded to
identify patients at increased risk of delayed contrast elimination (see
section 3). To explore the clinical relevance of delayed contrast elimination,
1-month eGFR decline and incidences of dialysis and mortality will be compared
amongst matched pairs between subgroups categorized according to elimination
time.

TEMPOS is a single centre, observational, cohort study at Maastricht UMC+,
amongst patients referred for an elective procedure with intravascular
iodinated contrast.

Contrast elimination will be determined by assays of contrast content in urine
samples. All urine will be collected during approximately 4 days: from first
urination after intravascular iodinated contrast administration until the time
of visit 2.5; a baseline urine sample will be collected before
contrast-administration (see Table 1). Renal function will be monitored using
venepuncture samples: serum creatinine will be measured before (baseline) and
during 5 days post-contrast, as well as at 1-month post-contrast. Both urine
and serum samples will be stored at the biobank Maastricht UMC+ for renal
damage marker assays.

The study will include 72 patients with eGFR <30 mL/min/1.73m2 (derived from
the MIRACLE study), 72 patients with eGFR 30-59 mL/min/1.73m2, and 72 patients
with eGFR >=60 mL/min/1.73m2. The latter two groups will be matched by age, sex
and contrast procedure type to the 72 eGFR <30 mL/min/1.73m2 patients. Each
patient will be followed for approximately one month.

To explore the clinical relevance of delayed contrast elimination, 1-month eGFR
decline and incidences of dialysis and mortality will be compared amongst
patient subgroups categorized according to contrast elimination time. It is
unknown what contrast elimination times will be. Contrast elimination will
therefore be considered delayed if contrast elimination time exceeds the
patient group median value, and vice versa. Furthermore, the following
subgroups will also be evaluated: 1. Normal (contrast-free urine within <=24
hours); 2. Delayed (contrast-free urine within 24-48 hours); 3. Severely
delayed (contrast-free urine >48 hours). Subgroup cut-off values may be added
at a later stage (e.g., in the event of many or no patients with elimination
>48 hours).

Patients with eGFR <30 mL/min/1.73m2 are most at risk of renal injury after
intravascular iodinated contrast material injection; patients with eGFR 30-59
mL/min/1.73m2 are considered at moderate to ow risk, and patients with eGFR >=60
mL/min/1.73m2 are considered to be at low to no risk. Whereas such contrast
administration appears to be safe for the majority of patients even with eGFR
<30 mL/min/1.73m2, reports of individuals with post-contrast adverse events
persist. It may be that the distinguishing characteristic is contrast
retention.

In order to determine elimination time and identify which patients retain
contrast, patients will be asked to collect urine every time they naturally
urinate and to note time and date on the container provided. Urine will be
collected for approximately 4 days: from first urination after intravascular
iodinated contrast administration until the study visit on day 5 post-contrast
(Table 1). Urine containers will be collected during study visits.

Longer elimination time of contrast will potentially increase renal toxicity.
Therefore, renal function (serum creatinine in venepuncture blood sample) will
be determined during 5 days and at 1-month post-contrast (Table 1). One
baseline and one post-contrast venepuncture blood sample and serum creatinine
measurement are standard care for all patients with eGFR <60 mL/min/1.73m2 (see
Table 2). The risks of venepuncture and participation in this study are deemed
negligible.

Patients are not expected to personally benefit from participating in this
study, although their renal function will be monitored extra closely. Results
of this study may help better determine the causal relationship between
contrast exposure and nephrotoxicity, identify which individual patients are at
risk, and help to better determine safety of intravascular iodinated contrast
administration in future.