D
Athavale, SK Sivapunniam, TJ Beattie
Renal Unit, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ
Corresponding Author: TJ Beattie Email: jim.beattie@yorkhill.scot.nhs.uk
SMJ 2007 52(2): 56
Anti-pyretic and analgesic usage of non-steroidal anti-inflammatory drugs (NSAIDs) is commonplace in paediatric practice. The nephrotoxic effects of Non-steroidal anti-inflammatory drugs (NSAIDs) are well documented and increasingly cases of Acute Renal Failure (ARF) precipitated in volume-depleted states in children following NSAIDs usage is being recognised. We report a significant case of ARF in a volume depleted child precipitated by a single dose of Diclofenac, highlighting an important clinical message – adequate hydration is essential, prior to administration of any NSAID, in order to prevent acute renal failure.
Key
words: Renal Failure; Dehydration; Non-Steroidal Anti-inflammatory Drugs
Introduction
The
nephrotoxic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are well
known. Ibuprofen is widely used as an analgesic and antipyretic, and there have
been several documented case reports of ibuprofen causing renal impairment in
volume depleted children.1-3 Diclofenac is generally restricted to
use in paediatric rheumatology practice or as peri-operative analgesia.4
We would like to report a case of acute renal failure secondary to a single dose
of diclofenac in a volume depleted child and highlight the importance of
ensuring adequate hydration in children receiving diclofenac.
A
7-year-old girl, previously well, presented with generalised abdominal pain,
following a 7 day history of vomiting and intermittent diarrhoea. On admission
she was alert though distressed, tachycardic, and well perfused with dry mucous
membranes. There was generalised abdominal tenderness but no rebound or guarding
and her blood pressure was 134/74mmHg (95th centile, 114/75mmHg).
Investigation showed haemoglobin of 15.1gm/dl, haematocrit of 45%, and a normal
white cell count. Plasma urea and creatinine were 6.1mmol/l and 73umol/l
respectively, and urinalysis showed 3+ketones, 1+protein, and 4+ blood and urine
culture subsequently showed a significant growth of E.Coli. She was commenced on
maintenance intravenous fluids and given 25mg diclofenac (0.83mg/kg) per rectum
as analgesia and a single dose of 2gm intravenous Ceftriaxone empirically.
.
30
hours after admission she became anuric with a concomitant rise in plasma
creatinine to 180umol/l. Oral Ibuprofen 150mg was administered, 10 hours later,
for ongoing abdominal pain. Blood pressure remained consistently elevated
(systolic 114 – 134 and diastolic 75 – 92 mmHg.). 48 hours after admission,
she was transferred to our unit following a further rise of plasma creatinine to
243umol/l. Following referral she required 5 days of peritoneal dialysis, with a
peak plasma creatinine of 779umol/l. Blood pressure was controlled with
Nifedipine. Renal ultrasound was normal and percutaneous renal biopsy showed
normal glomerular perfusion and morphology, however, the proximal tubules showed
loss of epithelial cell nuclei with sloughing in keeping with acute tubular
necrosis. Immunofluorescence studies were negative. She was anuric for a total
of 5 days, but subsequently diuresed spontaneously with a reduction in plasma
creatinine to 63umol/l on the 8th day following initial admission. Follow-up
urinanalysis was normal. Nifedipine was discontinued on discharge the following
day.
On
subsequent review, 10 days later, she was normotensive (100/45mmHg) and plasma
creatinine was 51 umol/l. EDTA clearance study at 1 year was normal and she was
discharged from follow-up.
Prostaglandins have a negligible role in renal function in euvolemic states but in intravascular depleted states renal plasma flow is maintained by a balance between the vasoconstrictor influence of the renin-angiotensin system (RAS) and the vasodilatory effects of prostaglandins. NSAIDs including Diclofenac inhibit prostaglandin synthesis and in volume depleted states may precipitate acute renal failure (ARF) particularly in patients with pre-existing renal disease.5
Oral
or rectal Diclofenac is licensed for use in children at doses of 300mcg-1mg/kg6,
and although there have been comparative trials of rectal diclofenac usage for
peri-operative analgesia, limited information exists on the bioavailability in
children.4
Our
patient had no pre-existing renal disease, and on presentation had evidence of
intravascular volume depletion with raised haematocrit and plasma creatinine.
Although the relative hypertension noted on presentation could have been
accounted for by the abdominal pain, the persistence of hypertension suggests
activation of the RAS in response to volume depletion. The prodromal illness was
consistent with acute gastroenteritis, with no evidence of pyelonephritis
clinically and histologically. A single therapeutic dose of Diclofenac was
administered for analgesia, following which she became anuric and developed
dialysis dependent ARF. She also received an additional dose of Ibuprofen as
analgesia but at the time of administration, she was already anuric with an
elevated plasma creatinine of 180ummol/l.
ARF
after Ibuprofen and Ketoprofen administration has been reported in volume
depleted children usually after multiple doses. Moghal et al1
recently reported a case following six doses of ibuprofen but in a previous
report from the same author3, 3 cases of ARF were reported, two after
a single dose of ibuprofen, one of whom required haemodialysis for a total of 5
weeks. Ulinski et al2 reported 7 cases, 6 of whom had no underlying
renal disease. All received multiple doses with a median (range) treatment
duration of 3(1-5) days, and one needed a single haemodialysis treatment.
In our case, a single therapeutic dose of Diclofenac was sufficient to precipitate ARF in a volume depleted child and the renal failure was likely to have been exacerbated by the Ibuprofen dose. A case of diclofenac causing ARF has not been commonly reported in children. Krause et al describe two patients where multiple doses of diclofenac in conjuction with another NSAID caused renal impairment with complete recovery.7 Diclofenac and NSAIDs need to be prescribed with caution in cases where volume depletion may exist as even a single dose may cause renal failure and it is essential to ensure adequate hydration of children prior to administration.
1. Moghal NE, Hegde S, Eastham KM. Ibuprofen and acute renal failure in a toddler.Arch Dis Child 2004; 89:276-7.
2. Ulinski T, Guigonis V, Dunan O, Bensman A. Acute renal failure after treatment with non-steroidal anti-inflammatory drugs. Eur J Pediatr 2004;163:148-50.
3. Moghal NE, Hulton SA, Milford DV. Care in the use of ibuprofen as an antipyretic in children. Clin Nephrol 1998; 49:293-5
.4. Litalien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti-inflammatory drugs in children. A comparison with paracetamol. Paediatr Drugs 2001;3(11):817-58.
5. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106:13S-24S
6. Medicines for Children. RCPCH 2003.
7. Krause I, Cleper R, Eisentein B, Davidovits M. Acute renal failure, associated with non-steroidal anti-inflammatory drugs in healthy children. Pediatr Nephrol. 2005;20(9):1295-8