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Indian Pediatr 2013;50:
1051-1052 |
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Rasburicase for Acute Kidney Injury
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Rajiv Sinha and *Priya Dugar
Vision Care Hospital and Institute of Child Health,
Kolkata, India.
Correspondence to: Dr Rajiv Sinha, 37, G Bondel Road,
Kolkata 700 019, India.
Email: [email protected]
Received: May 09, 2013;
Initial review: July 01, 2013;
Accepted: July 18, 2013.
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Background: Acute kidney injury (AKI) continues to have significant
mortality and morbidity and the search is on for any novel therapeutic
intervention. Case characteristics: Two cases of AKI with
elevated SUA (serum uric acid). Intervention: Rasburicase.
Outcome: In Case 1 (late preterm male with AKI) rasburicase resulted
in a significant reduction of SUA along with improvement in renal
parameters. In Case 2 (6 yrs old boy with multi organ failure),
rasburicase failed to provide any significant benefit despite fall in
SUA.Message: The effect of rasburicase in AKI needs to be studied.
Keywords: Acute kidney injury, Child,
Rasburicase.
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Incidence of acute kidney injury (AKI) remains
high and the search is still on for a specific therapy which will avoid
dialysis and decrease the associated morbidity and mortality [1].
Recently few case reports have shown rasburicase (recombinant urate
oxidase) to be effective in various forms of AKI [2-7] with raised serum
uric acid. We herein report our experience of using rasburicase in 2
children with AKI (non-tumour lysis syndrome related).
Case Report
Case 1: A late preterm male baby was admitted
on day 4 (D4) with anuria and progressive body swelling from D2. The
baby was born by normal delivery with an APGAR of 6 at 10 min. On
admission his mean arterial pressure (MAP) was 35 mmHg, creatinine 5.8
mg/dL, potassium 6.5 mmol/L and sodium 121 mmol/L. He stayed anuric
despite fluid boluses and ionotropes. Usual AKI measures were initiated
along with urgent medical steps for reducing serum potassium. Anuria
persisted even after 24 hours, with worsening renal parameters (creatinine
peaked at 6.3) and hence peritoneal dialysis was considered. The parents
did not consent to an invasive procedure. As his serum uric acid was
elevated at 14 mg/dL, after parental consent and ruling out glucose 6
phosphate dehydrogenase (G6PD) deficiency, rasburicase was given on late
D5 at 0.2 mg/kg and within 12 hours he started to produce urine.
Subsequently there was a steady improvement in his urine output with a
concomitant fall in creatinine which became normal by D30 (Fig.
1). Post-rasburicase, serum uric acid was 0.5 mg/dL on D7 and
2.8 mg/dL on D10.
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Fig. 1 Urine output and creatinine
post-rasburicase in Case 1.
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Case 2: A 6-years-old boy with multiple
special needs was transferred from another hospital intubated and severe
respiratory distress. He had been anuric for 48 hrs with rising urea and
creatinine. He had quadriplegic cerebral palsy and epilepsy. On
admission to our institute, his transaminase was >7000, creatinine
phosphokinase 45000, INR was un-recordable, creatinine 3.01 mg/dL and
serum uric acid 8.9 mg/dL. A provisional diagnosis of rhabdomyolysis was
made but due to anuria, myoglobinuria could not be confirmed. His
ventilation was stabilized and because of impaired perfusion and low
arterial pressure he received normal saline boluses as well as inotropes.
Despite this he remained hemodynamically unstable and anuric with
worsening renal parameters along with significant coagulopathy. Dialysis
was contemplated but in presence of severe coagulopathy both
hemodialysis (as we do not have facilities of hemofiltration in our
unit) and peritoneal dialysis were considered risky. His uric acid on
the next day had risen to 9.7 mg/dL and after parental consent
rasburicase was administered at 0.2 mg / kg (G6PD level was normal)
around 24 hrs after admission. Despite a dramatic fall in uric acid (0.3
mg/dL by 24 hours) he passed 4 mL of urine within four hours with no
further improvement in urine output and renal parameters continued to
worsen. Sustained low efficiency dialysis (SLED) had to be ultimately
initiated by D3 of admission but he suffered from a massive pulmonary
bleed and died on D4 of admission.
Discussion
Rasburicase is a recombinant urate oxidase, an enzyme
which breaks down uric acid to 5-10 times more soluble allantoin.
Although it has become a standard intervention for
prevention / treatment of AKI secondary to tumor lyses syndrome [8] it
has only recently been proposed as a novel treatment modality for other
causes of AKI [2-7].
Over the last decade there has been increasing
experimental evidence suggesting alternative pathways for uric acid
induced AKI apart from the well-known intra tubular crystal deposition.
The proposed mechanism includes uric acid induced renal vasoconstriction
secondary to inhibition of neuronal nitric oxide synthase, and
thickening of pre-glomerular arterioles secondary to endothelial damage,
all of which results in impaired renal blood flow auto-regulation.
Elevated uric acid has also been shown to have pro-inflammatory property
including stimulating release of monocyte chemo-attractant protein-1
(MCP-1) [9]. Epidemiologically also it has been seen that elevated
preoperative uric acid ( ³7
mg/dL) is associated with a 35-fold increased risk for AKI in adults
undergoing cardiovascular surgery [9]. Further confirming the role of
uric acid in AKI, a recent randomized control trial among adults
undergoing cardiac surgery showed lower urinary AKI biomarker (NGAL) in
cases of pre-emptive reduction of uric acid particularly in patient with
impaired baseline glomerular filtration rate (<45mL/min/1.73m2)
[10].
A logical corollary from the above mentioned evidence
would be to explore whether treating hyperuricemia benefits established
AKI. This was first explored by Hobbs, et al. [2] and
subsequently there have been few more positive case reports [2-7].
However, as shown by the negative response in our Case 2, much more
needs to be learned before we adopt it routinely. Although we did not
experience any related side effects one should watch for anaphylaxis as
well as always document a normal G6PD levels before administrating
rasburicase [8] .
In conclusion, evidence is mounting in favour of uric
acid as a novel clinical biomarker and its estimation should be included
in any AKI work up. Despite the high cost (Rs 15,000 for 1.5 mg ampoule)
of rasburicase, if it can be demonstrated that it is effective in AKI
and can reduce need for dialysis, it is likely to prove to be cost
effective. Acknowledgements: Dr Amit Ray, Consultant
Neonatologist; Dr Bichitrovanu Sarkar, Consultant Pediatric Intensivist,
Vision Care Hospital, Kolkata; and Dr L Pandey for patient management.
Contributors: Both the authors have contributed,
designed and approved the manuscript.
Funding: None; Competing interests: None
stated.
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