Effect of Magnegita on Routine Laboratory Parameters

in Patients with Impaired Kidney or Liver Function

DELIA MARIA MINCA1, DANIELA ANCA PUSCASIU2*, SILVIU BRAD2, CARMEN SOFICA TATU2
1
Pius Branzeu County Clinical Emergency Hospital Timisoara, 156 Liviu Rebreanu Blvd., 300728, Timisoara, Romania
2
Victor Babes University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq., 300041, Timisoara, Romania

The aim of this study was to assess the effect of Magnegita (gadopentetate dimeglumine) on routine
laboratory parameters in patients with impaired kidney or liver function undergoing MRI scans. Seventy-one
patients were included from whom we collected blood samples for three times. Our study showed
statistically significant results for certain parameters at both measurements performed after the injection of
contrast agent. We conclude that monitoring of laboratory values in patients with kidney and liver impairment
after injection of gadopentetate dimeglumine may be helpful by allowing the medical personnel to prevent
serious adverse events.
Keywords: gadopentetate dimeglumine, laboratory parameters, chronic kidney failure, hepatitis C

Contrast agents are known to enhance signal resolution

and sensitivity of magnetic resonance imaging (MRI)
scans. Currently, gadolinium (Gd), a rare-earth metal of
the lanthanide series, is the most widely used metal for
the production of contrast agents [1]. Gadolinium is
administered in the form of stable chelates to prevent its
release in vivo [2, 3] through transmetallation, by which
the Gd3+ ion is displaced from its ligand by competing
endogenous metals: zinc, copper, calcium, and iron [4].
This may result in the deposition of toxic ion in liver, bone
and lymph nodes [5]. Not only the chelator prevents Gd to
reach the tissues, but it also allows for a faster renal
excretion [6].
Early studies [7-9] on gadopentetate dimeglumine (GdDTPA) have concluded it is safe and well tolerated.
However, minor and transient adverse reactions were
reported in some patients: asymptomatic dose-dependent
elevations in serum iron and bilirubin levels [9, 10], hyperor hypotension, weakness, conjunctivitis, local burning at
injection site, headache, nausea and vomiting, hives,
diffuse erythema or skin irritation, and respiratory
symptoms [11-13]. Only a few cases of life-threatening
anaphylactoid reactions were reported so far [14, 15], with
one fatality undoubtedly related to Gd-DTPA administration
[16]. Nevertheless, in 2006, a causative link has been
suggested by Grobner [17] between administration of
gadolinium-based contrast agents (GBCAs) and the
development of nephrogenic systemic fibrosis (NSF), a
disease characterized by progressive multiple-organ
fibrosis, in patients with severe renal impairment. Further
studies have found gadolinium deposits in cerebellum, skin,
kidney, liver, heart, lymph nodes and bones of NSF patients
[18-20]. The free gadolinium ion inhibits physiological
processes dependent on Ca2+ influx and concurrently
activates calcium-sensing receptors on hepatocytes,
kidney, thyroid, and parathyroid glands, fibroblasts and
pancreas [21]. In patients with severe renal dysfunction,
kidneys are unable to eliminate gadolinium due to its poor
water solubility [22]. At this adds the toxic effects on the
liver [23], where it both blocks phagocytosis by and
eliminates Kupffer cells [24]. However, a recent report [25]
on the safety of gadopentetate dimeglumine after 25 years

of clinical use and 120 million administrations confirmed

its excellent safety profile. The global yearly rate of NSF
cases in 100,000 administrations reported in the 2006 2011 period ranged between 0.3 (2009) and 0.1 (2011).
The incidence of NSF seems to be also related with the
use of higher than standard GBCA dose.
We here report the use of Gd-DTPA in 71 diagnostic
procedures by MRI in 50 patients with impaired renal or
liver function and 21 controls.
Experimental part
Materials and methods
This study evaluating the effect of gadopentetate
dimeglumine (Magnegita 500 mol/mL, Biokanol
Pharma GmbH) on routine laboratory parameters in
patients with impaired kidney or liver function versus
patients with normal kidney and liver function was
conducted in the Radiologica Plus Medical Imaging Centre
Timisoara, Romania from January 2014 to December 2015.
The study group was composed of 50 subjects, divided
into two subgroups: 25 patients with chronic kidney failure
(CKF) included in the National Dialysis Programme and 25
patients with hepatitis C (HCV). The 21 patients in the
control group had normal renal and liver functions.
Distribution of patients by demographic data is shown in
table 1. All patients were referred by their physicians for
abdominal MRI scans. All the patients have signed the
Informed Consent Form prior to inclusion in the study.
Inclusion criteria: patients aged 18-80, both genders;
not pregnant or breastfeeding, in case of women; had not
received an organ transplant; had not received any contrast
agent within 7 days; normal liver and kidney functions for
Table 1
DISTRIBUTION OF PATIENTS BY DEMOGRAPHIC DATA

* email: danielapuscasiu@yahoo.com; Tel.: +40-722 364 695

808

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Table 2
REFERENCE RANGES OF THE
STUDIED PARAMETERS

patients in the control group; willing to sign Informed

Consent Form; willing to provide three blood samples.
Exclusion criteria: patients who had a contrastenhanced MRI or CT scan seven days prior to inclusion in
the study; under chemo- or radiation therapy; had received
any investigational drug 30 days prior to the MRI scan.
Both subjects and controls received standard dose (0.1
mL/kg body weight) Gd-DTPA, provided as a sterile, stable,
clear, particle free solution in 20 mL vials. Each millilitre
contained 469 mg of Gd-DTPA and excipients: pentetic
acid, meglumine and water for injection. The contrast agent
was injected intravenously and patients were monitored
for adverse reactions (none recorded) during and 30 min
after the injection.
We have collected blood samples from each patient for
three times, namely shortly before the injection of the
contrast agent, then 30 min and 24 h after the injection.
Three blood samples were harvested each time from all
the patients, as follows: two samples of 3 mL each for
complete blood count (by laser flow cytometry; performed
on SYSMEX SF-3000 Hematology analyser) and one sample
of 6 mL for biochemistry tests (by spectrophotometry using
HITACHI 917 analyser; ionogram tests were performed by
ion selective electrode technology using EasyLyte Plus
analyser). We have then analysed 27 parameters (table 2)
by complete blood count, biochemistry and ionogram tests
using reagents from Diagon for hematology tests,
DiaSys Diagnostic Systems for biochemistry tests and

Medica for ionogram tests, according to the manufacturers

instructions.
As expected, we have found at baseline decreased or
increased levels of various parameters in patients included
in the study group according to their pathologies (table 3).
In the CKF subgroup we found elevated levels of both
creatinine and urea in 23 patients, while four patients had
blood glucose values suggestive of diabetes mellitus (>126
mg/dL. In the HCV subgroup, ten patients had higher-thannormal levels of both ALT and AST.
Elevated serum chloride levels were recorded in 11
patients in the control group, as well as decreased levels
of eosinophil count in ten patients.
Results and discussions
Second measurement
After harvesting blood samples from all the patients for
the second time, namely 30 min after the injection of
Magnegita, we have analysed the same 27 parameters
and compared the results with those obtained at baseline.
Statistically significant results were obtained for 17 of the
parameters (table 4). Nevertheless, when comparing the
values recorded at the first two measurements in all the
patients in the study group, we found changes have
occurred in virtually all the subjects. Urea and blood glucose
increased in all the subjects in the CKF subgroup, as well
as in more than half of the HCV patients. Creatinine elevated
in 92% of the patients with chronic kidney failure, whereas

Table 3
ALTERED PARAMETERS AT
BASELINE IN THE TWO
SUBGROUPS

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809

Table 4
PATIENTS WITH ALTERED
PARAMETERS AT THE SECOND
MEASUREMENT

lymphocyte count and percentage, monocyte count, RBC,

HGB, HCT, ALT, AST, sodium and chloride increased in over
50% of the subjects in this subgroup. Similarly, 76% of the
patients in HCV subgroup experienced increases in
lymphocyte percentage. In the control group, neutrophil
percentage elevated in 81%, monocyte count and blood
glucose in 67%, whilst urea and potassium in 52% of the
patients.
Decreases were recorded in the HCV subgroup, where
neutrophil percentage, RBC and RDW dropped in about
two thirds of the subjects. Over 50% of the subjects in this
group had lower HGB, HCT, ALT and AST, sodium and
chloride compared with baseline. Calcium also decreased
in more than half of the CKF subgroup. Several parameters
decreased in all controls (RBC, HGB, ALT, AST and
calcium), lymphocytes (count and percentage) and HCT
dropped in over 90%, while creatinine decreased in 76%,
sodium and monocyte count in 67%, RDW in 62%, urea
and chloride in 52%.
Mean percentage increase and decrease were
calculated for these 17 parameters. All parameters have
increased and/or decreased in most subjects by various
rates. The most altered parameters in terms of number of
patients with higher levels and mean percent increase at
second measurement were lymphocyte count (16;
16.45%) and percentage (15; 10.35%) in the CKF subgroup
and monocyte count in both subgroups (CKF-16; 16.82%;
HCV-12; 44.64%). The greatest mean percentage decrease
in both subgroups was found for monocyte count (CKF-7;
21.72%; HCV-11; 22.34%). Same parameters exhibited
highest mean percentage decreases in the control group
as well (lymphocyte count-20; 18.7%; lymphocyte
percentage-18; 13.3%; monocyte count-19; 16.5%).

810

Third measurement
After analysing all the parameters 24 h after the injection
of Magnegita, we have compared the results with those
obtained at baseline and at the second measurement.
Statistically significant results were found for 14 of the
parameters (table 5).
Similarly to the second measurement, all parameters
were altered in most of the subjects. The greatest numbers
of subjects with increased levels, ranging from 60% to 100%
of the subjects, were found in the CKF subgroup (in
descending order): urea, creatinine (both raised in all
subjects), RBC (which was also higher in 60% of the HCV
subjects), HGB, HVT, sodium, chloride, lymphocyte
percentage, monocyte count, and AST. On the other hand,
the highest percentages (between 60 and 72%) of subjects
with decreased levels were recorded in the HCV subgroup,
as follows: chloride, lymphocyte percentage, ALT, urea and
calcium. Compared with the second measurement, five
of the parameters remained increased in over 50% of the
CKF subjects (urea, creatinine, lymphocyte percentage,
sodium and monocyte count), but none of those showing
decreases at the first two measurements. Finally, RBC was
increased in both subgroups at the third measurement,
but not at the second one, when it was decreased in most
of the HCV subjects. Total serum proteins (81%), monocyte
count (67%), lymphocyte percentage, HCT and AST (by
57% each) dropped, but potassium (86%), sodium (81%)
and chloride (67%) increased in more than half of controls.
Monocyte count remained the most altered parameter
as regards the number of patients affected coupled with
the mean rate of change towards baseline in both
subgroups (HCV-14; 62%; CKF-15; 33%), followed by
lymphocyte percentage in the CKF subgroup. The highest

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Table 5
PATIENTS WITH ALTERED PARAMETERS
AT THE THIRD MEASUREMENT

decrease rate in the control group was much lower

(31.25% for monocyte count). This is also true for the
greatest increase rate recorded in this group (34.81% for
serum urea). The only mean percentage in the control group
higher than 10% was that calculated for the monocyte
count (11%).
Gadolinium-based contrast agents are routinely used in
magnetic resonance imaging [26]. Patients with end-stage
renal disease often undergo such examinations [27].
GBCAs are normally eliminated unmetabolized via kidneys
[28], with half-lives of approximately 1.5 h in people with
normal renal function [29]. In patients with renal
impairment, half-life of these contrast agents can be
delayed to several hours [27].
Gadolinium may interfere with various laboratory
parameters, although changes are minor and transient, as
shown in a study by Proctor et al. [30], who found GdDTPA to interfere with iron and a manual colorimetric zinc
assay. However, the other parameters measured showed
no significant interference. Russel and colleagues [7] found
transient increases in serum iron, but no changes in other
laboratory parameters. In a retrospective study [31], a
transient decrease in serum creatinine levels recorded
before and within 1 day after Gd-DTPA administration was
seen in patients with renal impairment, although Haustein
and colleagues [32] previously found no changes in mean
values or clinically relevant changes in individual patients
for serum creatinine and alanine aminotransferases.
We have found statistically significant results in 17
parameters 30 min post-injection and in 14 parameters at
24 h. Changes have occurred in most of the subjects, with
patterns of increases and decreases largely related to the
pathologies of subjects in the two study subgroups. Minor
alterations of most parameters were also seen in most
controls. Mean levels were outside the normal range for a
series of parameters at all three measurements in the study
group, while the mean level of serum chloride slightly
exceeded the normal range, as it was at the upper normal
value since the baseline measurement in the control group.
REV.CHIM.(Bucharest)67 No. 4 2016

The most altered parameters as regards the number of

patients affected and the mean rate of change towards
baseline were monocyte count in all groups at both
measurements, lymphocyte count (30 min post-injection)
and lymphocyte percentage in the CKF subgroup (both
measurements).
Conclusions
This study aimed to assess the effect of Magnegita on
routine laboratory parameters in people with kidney or liver
impairment. Although alterations were seen in virtually all
subjects and controls 30 min and 24 h after injection of
contrast medium, the highest mean increases or
decreases were mainly related to the pathologies of the
subjects. Several very high variations between baseline
and subsequent measurements were recorded in individual
subjects. However, none of these have proved to critically
influence the health status of patients included in this study.
Despite the fact that no serious adverse events occurred
during this study, we believe the monitoring of routine
laboratory values of patients with kidney and liver
impairment after injection of gadopentetate dimeglumine
may be helpful by allowing the medical personnel to rapidly
take the appropriate measures in order to prevent serious
adverse events.
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Manuscript received: 11.04.2016

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