Professional Documents
Culture Documents
Ceftriaxone and Acute Renal Failure in Children: Authors
Ceftriaxone and Acute Renal Failure in Children: Authors
Ceftriaxone and Acute Renal Failure in Children: Authors
KEY WORDS
acute renal failure, child, ceftriaxone
ABBREVIATIONS
PARFpostrenal acute renal failure
RUCretrograde ureteral catheterization
TMStandem mass spectrometric
Dr Li collected the data and wrote the article; Profs Zhou and
Yuan performed the treatment of the children; Dr Chen and Prof
Jiang carried out the ceftriaxone detection by mass
spectrometric analysis; Prof Zhang conceptualized the article;
and all authors approved the nal manuscript as submitted.
abstract
OBJECTIVE: Our aim was to evaluate the clinical prole, treatment,
and outcome of ceftriaxone-associated postrenal acute renal failure
(PARF) in children.
METHODS: We retrospectively studied 31 consecutive cases from 2003
to 2012 for PARF after ceftriaxone treatment. There was no past history
of urolithiasis or nephropathy in these children.
www.pediatrics.org/cgi/doi/10.1542/peds.2013-2103
doi:10.1542/peds.2013-2103
Accepted for publication Jan 14, 2014
Address correspondence to Wen Zhang, MD, Department of
Pediatric Surgery, Tongji Hospital, Tongji Medical College,
Huazhong University of Science and Technology, No 1095 Jiefang
Rd, Tongji Hospital, Wuhan 430030, China. E-mail:
wenzhang09@126.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2014 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated
they have no potential conicts of interest to disclose.
e917
Our aim was to study the clinical features, treatment, and outcome of
ceftriaxone-associated PARF in children.
METHODS
e918
LI et al
RESULTS
Baseline Characteristics, Primary
Diseases, and Ceftriaxone
Administration
Among the 31 cases of ceftriaxoneassociated PARF, 23 were boys and 8
were girls. The mean age was 5.1 years
(range, 112 years). The primary
diseases for which ceftriaxone was
administered included 12 cases of
pneumonia, 5 cases of upper respiratory tract infections, 5 cases of sinusitis, 1 case each of meningitis,
parotitis, and left arm trauma, and 6
postoperative cases (3 for hypospadias, 2 for appendicitis, and 1 for femoral fracture). Family histories revealed
a history of urolithiasis in parents of 3
cases. None of the siblings had urinary
calculi.
The average time of ceftriaxone administration was 5.2 days (range, 37
days). The exact doses of ceftriaxone
administration were available in 13 cases
and ranged from 70 to 100 mg/kg/d
(mean, 86.7 mg/kg/d). The average time
from the rst day of ceftriaxone administration to anuria was 5.4 days
(range, 39 days).
Clinical Features
The clinical symptoms included a sudden onset of anuria for at least 24 hours
(31/31), ank pain (.3 years old, 25/25;
17 bilateral and 8 unilateral), excessive
crying (,3 years, 6/6), and nausea
and/or vomiting (19/31). Nine children
had mild dehydration and 5 were
edematous. Severe dehydration was
not recorded in any case.
Renal ultrasonography revealed bilateral mild hydronephrosis in 6 children
and unilateral mild hydronephrosis in
19 children. Six children had normal
renal ultrasonographs. The average
anteroposterior diameter of the pelvis
ARTICLE
was 0.64 cm (range, 0.41.2 cm). Ureteric calculi were found in 11 children.
The diameters of calculi ranged from
0.2 to 0.6 cm (mean, 0.3 cm). Biliary
ultrasonography was performed in 22
children, among which 4 were found to
have biliary pseudolithiasis. Abdominal
radiographs showed uid levels in 3
cases and no calculus was observed in
any of the patients (Table 1).
Treatment and Effectiveness
Nine patients began to urinate and recovered after 1 to 4 days of pharmacotherapy.
Twenty-one children who were resistant
to pharmacotherapy and had serum
creatinine .500 mmol/L required RUC
by cystoscopy. Five children had serum
creatinine levels above 500 mmol/L at
the time of admission. Sixteen children
(mean age, 4.4 6 2.0 years) underwent
bilateral RUC, and 5 children (mean
age, 8.2 6 2.9 years) underwent unilateral RUC. Unilateral RUC was used in
these 5 children as only 1 side could be
catheterized; a catheter could not be
inserted into the other side owing to an
edema of the ureterovesical orice and
calculi blockage. These 5 children were
also signicantly older than the other
16 children (P , .01). Once the catheters were in situ, normal urination
returned and the situation improved
accordingly in children who underwent
bilateral and unilateral catheterization.
The catheters were removed after 3 to
5 days.
RUC failed on both sides in 1 patient,
a 10-year-old boy, owing to dense calculi
blocking the ureteic orices. After
several attempts to catheterize the
patient, the orices of the ureter became edematous and started to bleed.
This child was referred for hemodialysis. After 3 sessions of hemodialysis on
alternative days, normal urination was
re-established.
The mean treatment duration was 1.8
days (range, 17 days). The mean
DISCUSSION
Several studies have shown ceftriaxone
to cause biliary pseudolithiasis2,3 and
nephrolithiasis.47 However, ceftriaxoneassociated PARF911 has been rarely
reported. In this study we identied
31 children who had PARF who had
e920
LI et al
Gender
M
M
F
M
M
M
M
M
M
F
M
M
F
M
F
M
M
M
M
M
M
F
F
M
M
M
F
M
F
M
M
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
8
2
3
5
12
2
7
4
7
1
8
6
6
10
3
7
1
3
5
4
7
2
3
4
4
9
5
8
3
6
2
Age, y
Days of Ceftriaxone
Treatment
5
4
4
5
3
5
4
3
6
6
5
7
4
4
6
7
7
7
6
5
5
4
5
7
5
4
5
7
4
7
6
Ceftriaxone Doses,
mg/kg/d
82.6
87.0
88.9
95.5
96.6
83.1
86.3
84.7
70.4
96.8
100
73.5
82.0
5
4
4
4
3
4
4
3
6
6
7
9
5
5
6
8
7
6
6
5
5
5
5
8
5
5
5
6
4
5
6
Time From
Ceftriaxone
Administration
to PARF, d
Anuria
Flank Pain
or Crying
Left 0.8
Right 0.5
Left 0.8
Right 0.6
Right 1.0
Right 0.5
Left 1.0, right 0.4
Right 0.4
Left 0.6
Left 0.4
Right 0.5
Left 0.4
Left 0.7
Left 0.8, right 0.6
Left 0.6, right 0.8
Left 0.4
Left 0.9, right 0.5
Right 0.6
Left 0.6, right 0.8
Right 0.4
Hydronephrosis, cm
Right 0.7
Right 0.4
Left 0.6, right 1.2
Left 0.5
Right 0.9
Vomiting
Biliary pseudolithiasis
Biliary pseudolithiasis
Right 0.6
Left 0.2
Left 0.3
Fluid level
Fluid level
Biliary pseudolithiasis
Biliary pseudolithiasis
Fluid level
Other Clinical
Findings
Right 0.2
Right 0.3
Left 0.4
Right 0.4
Left 0.2
Left 0.2
Right 0.3
Left 0.2
Ureteric Calculi, cm
Right RUC
Pharmacotherapy
Bilateral RUC
Bilateral RUC
Right RUC
Pharmacotherapy
Bilateral RUC
Bilateral RUC
Bilateral RUC
Bilateral RUC
Pharmacotherapy
Bilateral RUC
Bilateral RUC
Hemodialysis
Bilateral RUC
Bilateral RUC
Bilateral RUC
Pharmacotherapy
Bilateral RUC
Left RUC
Pharmacotherapy
Pharmacotherapy
Bilateral RUC
Pharmacotherapy
Bilateral RUC
Left RUC
Pharmacotherapy
Left RUC
Bilateral RUC
Bilateral RUC
Pharmacotherapy
Treatment
ARTICLE
FIGURE 1
Stone analysis by TMS. Urinary sediment samples from a patient were washed and dissolved in 1% formic
acid solution. Ceftriaxone calcium dissolved in 1% formic acid solution was used as a positive control. AB
Sciex 4000 Q-Trap instrument was used for TMS analysis. The Q1 scan showed ceftriaxone parent ion
with mass charge ratio 553.0 in both A, control and C, patient sample. Product ion scans further showed
that in the B, control and D, patient sample, the fragment ions (fragment of ceftriaxone) were similar. Cps,
counts per second; Da, dalton; m/z, mass charge ratio.
this view, we initiated pharmacotherapy for all children upon diagnosis, and
9 children responded well. In the other
children, the ceftriaxone stones were
found to be more compact and
obstructed the urinary tract. Their
ureteral orices had inammatory
swelling under cystoscopy, which
might have aggravated the obstruction.
Pharmacotherapy aimed to dilate the
ureters and relieve spasm (anisodamine),
relieve edema of the renal pelvis
and ureter (albumin and low dose of
dexamethasone), and most importantly,
prevent complications such as acidosis
(sodium bicarbonate) and urinary
tract infections (antibiotics). Once
the ceftriaxone administration is
stopped, swelling of the ureteral orices subsides, and stones get expelled,
thus relieving the symptoms. The
pharmacotherapy helps to maintain
the homeostasis during this waiting
period. Through pharmacotherapy use
alone, 9 children in this study recovered
6. Mohkam M, Karimi A, Gharib A, et al. Ceftriaxone associated nephrolithiasis: a prospective study in 284 children. Pediatr
Nephrol. 2007;22(5):690694
7. Gargollo PC, Barnewolt CE, Diamond DA.
Pediatric ceftriaxone nephrolithiasis. J Urol.
2005;173(2):577578
8. Acun C, Erdem LO, Sogut A, Erdem CZ,
Tomac N, Gundogdu S. Ceftriaxone-induced
biliary pseudolithiasis and urinary bladder
sludge. Pediatr Int. 2004;46(3):368370
9. Akl KF, Masri AT, Hjazeen MM. Acute urine
retention induced by ceftriaxone. Saudi
J Kidney Dis Transpl. 2011;22(6):12261228
10. Li ZL, Li HL, Chen HW, et al. Anuria and abdominal pain induced by ceftriaxoneassociated ureterolithiasis in adults. Int
Urol Nephrol. 2013;45(1):7376
11. Kapur G, Valentini RP, Mattoo TK, Warrier I,
Imam AA. Ceftriaxone induced hemolysis
complicated by acute renal failure. Pediatr
Blood Cancer. 2008;50(1):139142
CONCLUSIONS
This retrospective study showed that
ceftriaxone therapy could lead to PARF.
In ceftriaxone-associated PARF, conservative pharmacotherapy is helpful,
but when it fails, RUC is an effective
therapeutic option.
REFERENCES
1. Arvidsson A, Alvn G, Angelin B, Borg O,
Nord CE. Ceftriaxone: renal and biliary excretion and effect on the colon microora.
J Antimicrob Chemother. 1982;10(3):207
215
2. Cometta A, Gallot-Lavalle-Villars S, Iten A,
et al. Incidence of gallbladder lithiasis after
ceftriaxone treatment. J Antimicrob Chemother. 1990;25(4):689695
3. Schaad UB, Wedgwood-Krucko J, Tschaeppeler
H. Reversible ceftriaxone-associated biliary
pseudolithiasis in children. Lancet. 1988;2
(8625):14111413
4. Avci Z, Koktener A, Uras N, et al. Nephrolithiasis
associated with ceftriaxone therapy: a prospective study in 51 children. Arch Dis
Child. 2004;89(11):10691072
5. Chutipongtanate S, Thongboonkerd V. Ceftriaxone crystallization and its potential
role in kidney stone formation. Biochem
Biophys Res Commun. 2011;406(3):396
402
e922
LI et al
Citations
Reprints
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/early/2014/03/19/peds.2013-2103