Is it the right time to subject children with acute kidney injury to rasburicase trials?
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LETTER TO THE EDITOR Is it the right time to subject children with acute kidney injury to rasburicase trials? Tomasz Jarmoliński & Marcin Zaniew & Joanna Tousty & Dariusz Runowski Received: 15 January 2012 / Accepted: 16 January 2012 / Published online: 14 March 2012 # IPNA 2012 Sirs, We read with great interest the paper by Acosta and Hogg published in Pediatric Nephrology [1]. The authors de- scribed a case of hemolytic uremic syndrome and accelerat- ed recovery of renal function with the use of rasburicase (Ras), a uric acid (UA)-lowering agent. In our opinion, this report should receive special attention, because it expands the group of patients with acute kidney injury (AKI) who might benefit from such therapy. According to translational studies concerning destructive influence of UA on renal tubular structure and function [via intratubular precipitation, crystals internalization, cell necrosis, interstitial inflamma- tion, and vasoconstriction mediated by endothelin-1–nitric oxide (ET1-NO) imbalance] and data from studies on cancer patients with acute tumor lysis syndrome, one could hypoth- esize that there is a positive effect of reduce UA blood concentration on shortening the course of AKI also in patients without malignancies [2, 3]. Since the first article of Hobbs et al. on Ras in infants [4], few case reports have been published that consistently proved that therapy with Ras is efficacious in terms of decreasing serum UA and reversing AKI [5–7]. Given the increasing interest in Ras as a novel therapy of AKI in children, we would like also to share our institutional experience with four patients. In all below-reported patients, AKI of prerenal origin [according to the pediatric Risk, Injury, Failure, Loss, and End-Stage (pRIFLE) criteria] was accompanied by hyper- uricemia, which probably resulted from diminished glomer- ular filtration and might have negatively, simultaneously with other factors, affected renal function (Table 1). As in previous case series, after single intravenous injection of Ras (Fasturtec®, Sanofi Aventis) at a dose of 0.18– 0.22 mg/kg body weight, a rapid fall in serum UA concen- tration (11.68±2.83 mg/dl vs 0.43±0.71 mg/dl) and con- comitant decrease in serum creatinine and urea (1.63± 1.09 mg/dl vs 1.33±1.08 mg/dl and 139.25±60.25 mg/dl vs 117.50±54.73 mg/dl, respectively) were noticed. More- over, the urine output significantly increased compared with the 24-h periods before and after Ras injection (0.73± 0.41 ml/kg/h vs 3.03±3.53 ml/kg/h). In patient 1, continu- ous venovenous hemodiafiltration (CVV-HDF) was initiated because of anuria, severe fluid overload, and hyperkalemia. As polyuria appeared quickly after administration of Ras, renal replacement therapy (RRT) was discontinued after 10 h. In patient 2 AKI was preceded by gastroenteritis; however, renal failure was not reversed by fluid resuscita- tion. Kidney function started to improve quickly after low- ering serum UA level. Patients 3 and 4 had AKI in the course of relapsing nephrotic syndrome (NS). They were severely edematous; thus, treatment with plasma expanders, diuretics, and dopamine was started before Ras injection and then continued for the next 24 h. Nevertheless the intensity of this therapy was decreased after Ras injection so that we hypothesize that the immediate positive effect on recovery of renal function was due to the use of Ras. Ultimately, the kidney function completely normalized within 3–16 days in all four reported patients. Interestingly, patient 3 had previ- ously experienced a first episode of AKI during a relapse of NS, which required CVV-HDF. As in the other reports, we did not notice any adverse events related to Ras. On the basis of scant reports and our own observations, we conclude that a single dose of Ras seems to be reason- able in the initial management of children with hyperurice- mic AKI. However, to prove the extent of the beneficial role T. Jarmoliński (*) : M. Zaniew : J. Tousty : D. Runowski Department of Pediatrics, Nephrology and Toxicology, District Children’ s Hospital, Szczecin, Poland e-mail: [email protected] Pediatr Nephrol (2012) 27:1201–1202 DOI 10.1007/s00467-012-2127-7
Transcript of Is it the right time to subject children with acute kidney injury to rasburicase trials?
LETTER TO THE EDITOR
Is it the right time to subject children with acute kidneyinjury to rasburicase trials?
Tomasz Jarmoliński & Marcin Zaniew & Joanna Tousty &
Dariusz Runowski
Received: 15 January 2012 /Accepted: 16 January 2012 /Published online: 14 March 2012# IPNA 2012
Sirs,We read with great interest the paper by Acosta and Hoggpublished in Pediatric Nephrology [1]. The authors de-scribed a case of hemolytic uremic syndrome and accelerat-ed recovery of renal function with the use of rasburicase(Ras), a uric acid (UA)-lowering agent. In our opinion, thisreport should receive special attention, because it expandsthe group of patients with acute kidney injury (AKI) whomight benefit from such therapy. According to translationalstudies concerning destructive influence of UA on renaltubular structure and function [via intratubular precipitation,crystals internalization, cell necrosis, interstitial inflamma-tion, and vasoconstriction mediated by endothelin-1–nitricoxide (ET1-NO) imbalance] and data from studies on cancerpatients with acute tumor lysis syndrome, one could hypoth-esize that there is a positive effect of reduce UA bloodconcentration on shortening the course of AKI also inpatients without malignancies [2, 3]. Since the first articleof Hobbs et al. on Ras in infants [4], few case reports havebeen published that consistently proved that therapy withRas is efficacious in terms of decreasing serum UA andreversing AKI [5–7]. Given the increasing interest in Rasas a novel therapy of AKI in children, we would like also toshare our institutional experience with four patients.
In all below-reported patients, AKI of prerenal origin[according to the pediatric Risk, Injury, Failure, Loss, andEnd-Stage (pRIFLE) criteria] was accompanied by hyper-uricemia, which probably resulted from diminished glomer-ular filtration and might have negatively, simultaneously
with other factors, affected renal function (Table 1). As inprevious case series, after single intravenous injection ofRas (Fasturtec®, Sanofi Aventis) at a dose of 0.18–0.22 mg/kg body weight, a rapid fall in serum UA concen-tration (11.68±2.83 mg/dl vs 0.43±0.71 mg/dl) and con-comitant decrease in serum creatinine and urea (1.63±1.09 mg/dl vs 1.33±1.08 mg/dl and 139.25±60.25 mg/dlvs 117.50±54.73 mg/dl, respectively) were noticed. More-over, the urine output significantly increased compared withthe 24-h periods before and after Ras injection (0.73±0.41 ml/kg/h vs 3.03±3.53 ml/kg/h). In patient 1, continu-ous venovenous hemodiafiltration (CVV-HDF) was initiatedbecause of anuria, severe fluid overload, and hyperkalemia.As polyuria appeared quickly after administration of Ras,renal replacement therapy (RRT) was discontinued after10 h. In patient 2 AKI was preceded by gastroenteritis;however, renal failure was not reversed by fluid resuscita-tion. Kidney function started to improve quickly after low-ering serum UA level. Patients 3 and 4 had AKI in thecourse of relapsing nephrotic syndrome (NS). They wereseverely edematous; thus, treatment with plasma expanders,diuretics, and dopamine was started before Ras injection andthen continued for the next 24 h. Nevertheless the intensityof this therapy was decreased after Ras injection so that wehypothesize that the immediate positive effect on recoveryof renal function was due to the use of Ras. Ultimately, thekidney function completely normalized within 3–16 days inall four reported patients. Interestingly, patient 3 had previ-ously experienced a first episode of AKI during a relapse ofNS, which required CVV-HDF. As in the other reports, wedid not notice any adverse events related to Ras.
On the basis of scant reports and our own observations,we conclude that a single dose of Ras seems to be reason-able in the initial management of children with hyperurice-mic AKI. However, to prove the extent of the beneficial role
T. Jarmoliński (*) :M. Zaniew : J. Tousty :D. RunowskiDepartment of Pediatrics, Nephrology and Toxicology,District Children’s Hospital,Szczecin, Polande-mail: [email protected]
Pediatr Nephrol (2012) 27:1201–1202DOI 10.1007/s00467-012-2127-7
of Ras, a randomized controlled trial could provide strongevidence to justify the use of Ras in the pediatric population.For the appropriate stratification of such a multicenter trial,we recommend registering and analyzing the availableanecdotal data worldwide. Finally, in order not to miss thechance to treat these high-risk patients, we fully agree withAcosta and Hogg [1] that analysis of serum UA should beincluded in the panel of laboratory studies done in thesetting of AKI.
Acknowledgment The authors thank Prof. Eva Elenberg and Prof.Jochen Ehrich for good advice and comments.
References
1. Acosta AA, Hogg RJ (2012) Rasburicase for hyperuricemia inhemolytic uremic syndrome. Pediatr Nephrol 27:325–329
2. Park SH, Shin WY, Lee EY, Gil HW, Lee SW, Lee SJ, Jin DK, HongSY (2011) The impact of hyperuricemia on in-hospital mortality andincidence of acute kidney injury in patients undergoing percutane-ous coronary intervention. Circ J 75:692–697
3. Bosly A, Sonet A, Ross Pinkerton CR, McCowage G, Bron D, SanzMA, Van den Berg H (2003) Rasburicase (recombinant urate oxidase)for the management of hyperuricemia in patients with cancer. Reportof an international compassionate use study. Cancer 98:1048–1054
4. Hobbs DJ, Steinke JM, Chung JY, Barletta GM, Bunchman TE(2010) Rasburicase improves hyperuricemia in infants with acutekidney injury. Pediatr Nephrol 25:305–309
5. Ghirardello S, Ardissino G, Mastrangelo A, Mosca F (2010) Ras-buricase in the treatment of hyperuricemia of newborns. PediatrNephrol 25:1775
6. Hooman N, Otukesh H (2011) Single dose of rasburicase for treat-ment of hyperuricemia in acute kidney injury: a report of 3 cases.IJKD 5:130–132
7. Lin PY, Lin CC, Liu HC, Lee HC, Ho CS, Chiu NC, Peng CC,Huang FY, Tai JD (2011) Rasburicase improves hyperuricemia inpatients with acute kidney injury secondary to rhabdomyolysiscaused by ecstasy intoxication and exertional heat stroke. PediatrCrit Care Med 12(6):e424–e427
Table 1 Clinical data of patients treated with rasburicase (Ras)
Patientno.
Sex, age(years)
Cause of AKI Serum uric acid (mg/dl) Serum urea and creatinine(mg/dl)
Urine output (ml/kg/h) Time to normalizationof kidney function (days)
Before Rasa After Rasa Before Ras After Ras Before Ras After Ras
1 M, 2/12 Gram (−) sepsis 15.5 1.5 132 87 0.2 8.3 121.3 0.8
2 F, 10 FSGS and diarrhoea 9 0.1 61 56 1 0.9 51.3 1.1
3 M, 16 SSNS with NC 12 0.1 159 168 0.6 1.3 163.2 2.9
4 M, 5 SSNS with NC 10.2 0.02 205 159 1.1 1.6 30.7 0.5
FSGS focal segmental glomerulosclerosis without nephrotic syndrome (NS), SSNS steroid-sensitive NS, NC nephrotic crisis, AKI acute kidneyinjurya Serum uric acid, urea, and creatinine were measured 2 h before and 12 h after Ras injection; diuresis was estimated in 24-h periods before and afterRas
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