Safety and efficacy of renal replacement therapy for acute kidney injury in tumor lysis syndrome

Abdul Rahim Ahmed; Anwar Ul Haque; Farhana Amanullah; Sadiq Mirza; Faiza Rahman; Sadia Muhammad; Khadijah Abid

doi:10.4103/2589-9309.305900

BRIEF REPORT

Year : 2020 | Volume : 3 | Issue : 2 | Page : 67-70

Safety and efficacy of renal replacement therapy for acute kidney injury in tumor lysis syndrome

Abdul Rahim Ahmed¹, Anwar Ul Haque¹, Farhana Amanullah², Sadiq Mirza¹, Faiza Rahman¹, Sadia Muhammad³, Khadijah Abid⁴
¹ Department of Pediatric Intensive Care Unit, The Indus Hospital, Karachi, Pakistan
² Pediatric Nephrology, The Indus Hospital, Karachi, Pakistan
³ Pediatric Oncology, The Indus Hospital, Karachi, Pakistan
⁴ Department of Research Evaluation Unit, College of Physician and Surgeons, Karachi, Pakistan

Date of Submission	23-Apr-2020
Date of Decision	16-May-2020
Date of Acceptance	02-Sep-2020
Date of Web Publication	31-Dec-2020

Correspondence Address:
Abdul Rahim Ahmed
Department of Pediatric ICU, The Indus Hospital, Karachi
Pakistan

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2589-9309.305900

Abstract

Tumor lysis syndrome (TLS) defines a constellation of metabolic abnormalities resulting from tumor cell death leading to dreaded clinical complications, including acute kidney injury (AKI). The incidence of AKI in TLS varies from 14% to 76% and is associated with mortality in 36% cases, and up to 20% of patients require renal replacement therapy (RRT). This study was done to evaluate the therapeutic efficacy and safety of RRT in children with hematological malignancies who develop AKI with TLS. We retrospectively reviewed case records of patients, up to 5 years old,with AKI due to TLS who required RRT during November 2017–October 2019 admitted in the pediatric intensive care unit (PICU). The diagnosis of TLS was based on Bishop–Cairo criteria. The primary outcome was recorded as recovery of renal function. Out of total 400 patients with newly diagnosed hematological malignancy admitted in the PICU during the study period, 122 (30.5%) developed TLS with 32 (26.2%) having AKI, of which eight patients (2%) underwent dialysis. The mean estimated glomerular filtration rate on admission was 36.6 ± 9.8 mg/ml/1.73 m² with a mean urine output being 0.32 ± 0.1 ml/kg/h. Seven of eight patients underwent hemodialysis. All cases had successful RRT with normalization of renal function and establishment of adequate urine output. RRT is safe and effective in children for AKI with TLS with the recovery of renal functions.

Keywords: Acute kidney injury, pediatric oncology, renal replacement therapy, tumor lysis syndrome

How to cite this article:
Ahmed AR, Haque AU, Amanullah F, Mirza S, Rahman F, Muhammad S, Abid K. Safety and efficacy of renal replacement therapy for acute kidney injury in tumor lysis syndrome. Asian J Pediatr Nephrol 2020;3:67-70

How to cite this URL:
Ahmed AR, Haque AU, Amanullah F, Mirza S, Rahman F, Muhammad S, Abid K. Safety and efficacy of renal replacement therapy for acute kidney injury in tumor lysis syndrome. Asian J Pediatr Nephrol [serial online] 2020 [cited 2021 Jan 23];3:67-70. Available from: https://www.ajpn-online.org/text.asp?2020/3/2/67/305900

Introduction

Annually, 150 children in 1 million are diagnosed with cancer worldwide, with 100 cases/million population being reported in Pakistan.^[1],[2] Leukemia and lymphomas are the most common childhood cancer. These rapidly proliferating tumors are associated with tumor lysis syndrome (TLS), a life-threatening complication due to the rapid destruction and release of metabolites from cancer cells.^[3] This syndrome occurs during the early phase of diagnosis and treatment of malignant neoplasms with a reported incidence range from 37% to 63%.^[4]

Adequate hydration, use of allopurinol, and phosphate-binding agents are the cornerstone of treatment for the prevention of TLS. Acute kidney injury (AKI) may frequently complicate TLS and reported incidence varying from 14% to 76% with an associated high mortality rate of 36%.^[1],[2] It is caused by precipitation of uric acid, calcium phosphate, or hypoxanthine in the renal tubules.^[5] The infiltration of kidney by tumor deposits, exposure of nephrotoxic drugs, and altered hemodynamics worsen renal function, with around 20% requiring renal replacement therapy (RRT).^[3] RRT improves electrolyte abnormalities, reduces hyperuricemia and uremia, and optimizes fluid balance to facilitate chemotherapy administration.^[5] In most developing countries like Pakistan, there are scanty data on the use of RRT in the management of this complication.

Methodology

This retrospective study was done in the pediatric intensive care unit (PICU) at Indus Hospital, Karachi, which is a tertiary care hospital with one of the largest pediatric oncology units in the country. Medical records of children (1 month–15 years) with hematological malignancies with TLS associated with AKI requiring renal support from November 2017 to October 2019 were reviewed. Patients who did not develop TLS, AKI, or required RRT and those with preexisting renal conditions were excluded from the study. The study was approved by the institutional review board with approval number IRD_IRB_2019_12_007.

Definitions

TLS is defined based on Cairo–Bishop criteria and categorized as having clinical or laboratory TLS. Laboratory TLS was defined as the presence of at least two of the features, namely, hyperuricemia (serum uric acid >8 mg/dL), hyperphosphatemia (serum phosphorus >6.5 mg/dL), hyperkalemia (serum potassium >6 meq/L), and hypocalcemia (serum calcium <7 mg/dL). Clinical TLS required the presence of either renal dysfunction, arrhythmias, or features of leukostasis (seizure/intracranial bleed) along with laboratory criteria.^[1]

AKI is defined and staged according to the criteria of KIDGO 2012 using creatinine and urine output. The estimated glomerular filtration rate (eGFR) is calculated using the Schwartz “bedside” formula.^[6]Fluid overload was quantified using the following formula: (total amount of fluid intake [L] - the total amount of fluid output [L])/body weight at PICU admission [kg]) ×100.^[7]

Study protocol and data analysis

Standard preventive medical management given to all patients included hydration with 3000 ml/m²/day, allopurinol, phosphate binder, and correction of metabolic abnormalities. Patients that failed to respond to medical management for TLS and developed AKI were shifted to PICU for monitoring and considered for RRT after placement on double lumen hemodialysis (HD) catheter.

For continuous RRT (CRRT), the PrismaFlex^® system was used. For HD, the Fresenius Medical Care machine with standard bicarbonate-based dialysate and low flux dialyzer was used. Dialysis duration and prescription were based on discussion with the nephrologist.

After the improvement of metabolic profile, renal function (eGFR), and urine output, chemotherapy as per the protocol of the relevant malignancy was prescribed. RRT was discontinued once renal functions, urine output, and metabolic abnormalities were normalized.

The primary outcome was recorded as the recovery of renal function (eGFR) with adequate urine, whereas secondary outcomes include deaths due to primary widespread disease or due to hospital-acquired infection.

The data were entered into and analyzed using Statistical Package for Social Science (SPSS) version 21 (IBM Corp., Armonk, NY). Mean and the standard deviation were used for continuous variables, whereas frequency and proportions were used for categorical variables.

Results

Out of total 1095 PICU admissions during the study period, 400 were with newly diagnosed hematological malignancy. One hundred and twenty-two patients (30.5%) developed TLS, of which 32 patients (8%) had AKI and eight patients (2%) required RRT. The mean age of patients on admission was 10.6 ± 3.3 years, with seven (87.5%) males. The mean duration of PICU stay was 5.5 ± 1.4 days. The median pediatric risk of mortality III score on admission was 9 ± 1.5. Acute leukemia was diagnosed in five patients and the remaining three had Burkitt lymphoma. All patients had clinical and laboratory TLS, with renal dysfunction; however, arrhythmias and signs of leukostasis were not noted. All but two patients had Stage 3 AKI at admission to PICU with mean eGFR of 36.6 ± 9.8 mL/min and urine output was 0.32 ± 0.1 ml/kg/h. The median time to start RRT from admission was 16.0 ± 4.3 h [Table 1].

Table 1: Demographics and patient details

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Seven patients (87.5%) underwent HD with a mean of 4.1 ± 1.3 days and 3.1 ± 1.5 sessions, whereas one patient underwent 36 h of CRRT due to hemodynamic instability. All cases had successful RRT with no acute complications such as bleeding, hypotension, and disequilibrium syndrome. RRT was successfully discontinued in all patients after resolution of AKI. Normalization of eGFR with a mean of 96 ± 21.4 mL/min/1.73 m² and establishment of adequate urine output with a mean of 4.4 ± 0.7 ml/kg/h were noted. All patients were successfully given chemotherapy and most were shifted out to PICU.

Three patients later expired due to uncontrolled primary disease and four patients expired due to hospital-acquired infection [Table 1].

Discussion

We found that RRT is safe and effective in TLS complicated with AKI in acute leukemia and lymphoma patients where medical management failed. Although studies do document the incidence of TLS, there is a paucity of data regarding especially from developing countries regarding the use of RRT in the management of TLS complicated with AKI.^[1]

The target of RRT in TLS is to optimize electrolyte abnormalities, acidosis, and fluid balance.^[5] Both HD and CRRT have been successful in pediatric patients;^[2] however, CRRT is preferred for TLS-AKI patients because it mimics the physiological process of continuous removal of metabolites, simultaneously facilitating removal of fluids, and maintains steady hemodynamics. In contrast, CRRT is a continuous and costly process requiring trained staff and monitoring.^[8] In our study, most patients were hemodynamically stable, and due to high costs of running CRRT, HD was preferred and proved to an efficient and effective modality with no acute complications and return of normal renal functions.

Patients with TLS requiring RRT have higher mortality and longer stay compared to patients with TLS that respond to conservative therapy.^[9] In our study, around one-third of patients died during their ICU stay; however, most patients who had successfully transitioned out of the ICU later succumbed to hospital-acquired infections, which is similar to other studies.^[10] These secondary outcomes indicate that, despite good supportive care, high-risk patients that require early aggressive management, stringent infection prevention strategies are needed to avoid such poor outcomes, particularly in developing countries where high-quality critical care services are scarce and expensive.

Controversies exist regarding timing of initiation of RRT in children with AKI irrespective of cause with early as well as late approach each documented to have been used.^[11] In our study, early initiation within 24 h of presentation of the patient was successful in all patients who were effectively given chemotherapy within 2 days of RRT.

Several limitations including small sample size, single center, and retrospective nature were noted. Another important limitation is the unavailability of rasburicase in our setup, which is considered standard of care for the management of hyperuricemia in TLS.^[12] The strength of this study is the first report from pediatric oncology of developing countries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Saeed F, Vadsaria K, Siddiqui DE, Iftikhar S, Ali MS, Ashraf MS. Tumour lysis Syndrome in children with haematological cancers: Experience at a tertiary care hospital in Karachi. Chemotherapy 2018;11:14.
2.	Ozkan G, Ulusoy S, Sönmez M, Kaynar K, Karagülle M. Treatment of tumor lysis syndrome with the highest known uric acid level. Ren Fail 2010;32:895-8.
3.	Teo WY, Loh TF, Tan AM. Avoiding dialysis in tumour lysis syndrome: is urate oxidase effective?-A case report and review of literature. Ann Acad Med Singap 2007;36:679-83.
4.	Naeem B, Moorani KN, Anjum M, Imam U. Tumor lysis syndrome in pediatric acute lymphoblastic leukemia at tertiary care center. Pak J Med Sci 2019;35:899-904.
5.	Locatelli F, Rossi F. Incidence and pathogenesis of tumor lysis syndrome. Contributions to nephrology. 2005;147:61-8.
6.	Mian AN, Schwartz GJ. Measurement and estimation of glomerular filtration rate in children. Adv Chronic Kidney Dis 2017;24:348-56.
7.	Raina R, Sethi SK, Wadhwani N, Vemuganti M, Krishnappa V, Bansal SB. Fluid overload in critically Ill children. Front Pediatr 2018;6:306.
8.	Liang KV, Sileanu FE, Clermont G, Murugan R, Pike F, Palevsky PM, et al. Modality of RRT and recovery of kidney function after AKI in patients surviving to hospital discharge. Clin J Am Soc Nephrol 2016;11:30-8.
9.	Garimella PS, Balakrishnan P, Ammakkanavar NR, Patel S, Patel A, Konstantinidis I, et al. Impact of dialysis requirement on outcomes in tumor lysis syndrome. Nephrology (Carlton) 2017;22:85-8.
10.	Baqari SAS, Haque A, Ashraf MS, Alam MM, Fadoo Z. Clinical profile and short-term outcome of pediatric hyperleukocytic acute leukemia from a developing country. J Coll Physicians Surg Pak 2017;27:450-4.
11.	Bagshaw SM, Wald R. Strategies for the optimal timing to start renal replacement therapy in critically ill patients with acute kidney injury. Kidney Int 2017;91:1022-32.
12.	Cheuk DK, Chiang AK, Chan GC, Ha SY. Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer. Cochrane Database Syst Rev 2017;3:CD006945.