Daily serum phosphate increase as early and reliable indicator of kidney injury in children with leukemia and lymphoma developing tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006-2016) from a nephrological aspect. METHOD: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. RESULTS: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS-AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. CONCLUSION: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. A higher resolution version of the Graphical abstract is available as Supplementary information.

Survey of Anaphylaxis during Rasburicase Re-Administration in Patients with Hematological Malignancies Using a Japanese Claims Database.

Management of tumor lysis syndrome (TLS) associated with cancer chemotherapy for malignant tumors is important because of its potentially fatal course. The use of rasburicase, a recombinant urate oxidase, is recommended for TLS; however, because rasburicase is an enzymatic drug, one should be cautious of anaphylaxis during administration. Using claims data in Japan, we investigated the rate of rasburicase re-administration and the occurrence of anaphylaxis during re-administration in patients with hematopoietic malignancies in a multicenter setting. Re-administration of rasburicase was defined as administration after an interval of 21 days from the first dose. Of 373 patients, 18 were re-administered rasburicase (re-administration rate: 4.8%). No patient developed anaphylaxis. The median number of days from the first to the last dose of rasburicase was 256.5 days (interquartile range: 138.8-455.8 days). The median daily dose was 7.5 mg (4.5-11.3 mg), and the median total dose was 33.8 mg (19.1-64.1 mg). This claims database analysis revealed that the re-administration rate of rasburicase was low in Japanese patients with hematopoietic malignancies, suggesting that rasburicase was being used appropriately, and that associated anaphylaxis was not observed.

Serum phosphate level and its kinetic as an early marker of acute kidney injury in tumor lysis syndrome.

INTRODUCTION: Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied. METHODS: In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development. RESULTS: One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence. CONCLUSION: This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Rescue Therapies for AKI in Onconephrology: Rasburicase and Glucarpidase.

Tumor lysis syndrome (TLS) and high-dose methotrexate (HD MTX) toxicity can present with potentially severe complications, including acute kidney injury, in patients with malignancy. Guidelines for using rasburicase and glucarpidase as rescue therapies for TLS and HD MTX toxicity, respectively, are widely used by clinicians intending to mitigate organ toxicity and decrease morbidity and mortality as a consequence of cancer therapy. This review discusses the pathogenesis of TLS and HD MTX-associated toxicity, to understand the mechanism of action of these therapeutic agents and to review the currently available evidence supporting their use.

Lesão Renal Aguda por Síndrome da Lise Tumoral em Unidade de Terapia Intensiva- Conhecimento do Enfermeiro / Acute Kidney Injury due to Tumor Lysis Syndrome in the Intensive Care Unit - Nurses Knowledge / Lesión renal aguda por síndrome de lisis tumoral en la Unidad de Cuidados Intensivos - Conocimiento de las enfermeras

Objetivo: analisar a produção científica sobre a lesão renal aguda causada pela síndrome da Lise tumoral no paciente internado em unidade de terapia intensiva, bem como o conhecimento do enfermeiro sobre tal patologia. Método: Trata-se de um artigo de revisão integrativa realizado através da leitura de 30 artigos científicos retirados da Biblioteca Virtual de Saúde. Resultados: Identificouse a ocorrência da lesão renal aguda e síndrome de lise tumoral através das alterações metabólicas e hemodinâmicas nos pacientes internados na unidade de terapia intensiva e observou-se que não há publicações com relatos do enfermeiro sobre o conhecimento desta patologia. Conclusão: Apesar dos estudos atuais e a busca constante pelo conhecimento, sabe-se que a lesão renal aguda e Síndrome de Lise Tumoral é uma emergência oncológica com alta taxa de morbidade, onde a principal estratégia para melhorar a evolução de pacientes é estabelecer medidas profiláticas e o tratamento adequado com urgência. Deve existir uma análise contínua do enfermeiro, bem como de toda equipe, estratificação dos riscos e elaboração de protocolos de controles hidroeletrolíticos e laboratoriais para estabilização hemodinâmica do paciente oncológico na unidade de terapia intensiva.

Objective: to analyze the scientific production on acute kidney injury caused by tumor lysis syndrome in patients admitted to the intensive care unit, as well as the nurses' knowledge about such pathology. Method: This is an integrative review article carried out by reading 30 scientific articles taken from the Virtual Health Library. Results: The occurrence of acute kidney injury and tumor lysis syndrome was identified through metabolic and hemodynamic changes in patients admitted to the intensive care unit and it was observed that there are no publications with nurses' reports on the knowledge of this pathology. Conclusion: Despite current studies and the constant search for knowledge, it is known that acute kidney injury and Tumor Lysis Syndrome is an oncological emergency with a high morbidity rate, where the main strategy to improve the evolution of patients is to establish prophylactic measures and appropriate urgent treatment. There must be a continuous analysis of the nurse, as well as the entire team, risk stratification and elaboration of hydroelectrolytic and laboratory control protocols for hemodynamic stabilization of the cancer patient in the intensive care unit.

Objetivo: analizar la producción científica sobre la lesión renal aguda por síndrome de lisis tumoral en pacientes ingresados en la unidad de cuidados intensivos, así como el conocimiento de los enfermeros sobre dicha patología. Método: Se trata de un artículo de revisión integradora realizada mediante la lectura de 30 artículos científicos extraídos de la Biblioteca Virtual en Salud. Resultados: Se identificó la ocurrencia de daño renal agudo y síndrome de lisis tumoral a través de cambios metabólicos y hemodinámicos en pacientes ingresó en la unidad de cuidados intensivos y se observó que no existen publicaciones con informes de enfermeras sobre el conocimiento de esta patología. Conclusión: a pesar de los estudios actuales y la búsqueda constante de conocimiento, se sabe que la lesión renal aguda y el síndrome de lisis tumoral es una emergencia oncológica con una alta morbilidad, donde la principal estrategia para mejorar la evolución de los pacientes es establecer medidas profilácticas. y tratamiento urgente apropiado. Se debe realizar un análisis continuo de la enfermera, así como de todo el equipo, estratificación de riesgo y elaboración de protocolos de control hidroelectrolítico y de laboratorio para la estabilización hemodinámica del paciente oncológico en la unidad de cuidados intensivos.

Fatal tumor lysis syndrome in a patient with metastatic gastric adenocarcinoma

Tumor lysis syndrome is a well-characterized and potentially deadly complication of spontaneous or treatment-related tumor destruction, and it is most commonly associated with hematologic malignancies. Our case illustrates a rare example of fatal tumor lysis syndrome in the setting of metastatic gastric adenocarcinoma treated with radiation therapy. This case highlights the critical importance of identifying patients with solid organ malignancies at risk for tumor lysis syndrome and of early recognition and treatment of this syndrome.

Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress.

BACKGROUND: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. SUMMARY: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and - in high-risk cases - considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.

Spontaneous Tumor Lysis Syndrome in Blastoid-Variant Mantle Cell Lymphoma: Considerations for the General Internist.

Spontaneous tumor lysis syndrome (SPTLS) is a rare phenomenon that can manifest in rapidly proliferating hematological malignancies and solid tumors prior to initiating cytotoxic therapy. We encountered a patient who originally presented with diffuse lymphadenopathy, abdominal distention, and dyspnea, who had laboratory abnormalities suggestive of SPTLS. His peripheral flow cytometry and lymph node biopsy revealed blastoid-variant mantle cell lymphoma. Prior to initiating chemotherapy, acute kidney injury (AKI) and uric acid had improved with intravenous fluids and the initiation of allopurinol. However, after beginning chemotherapy, the patient developed a second AKI concerning for tumor lysis syndrome (TLS). He went on to have renal recovery and did not require renal replacement therapy. With the exception of case reports, there is limited evidence to guide general medicine clinicians who encounter cases of SPTLS. Expert-based guidelines are available to guide use of rasburicase, an uricase enzyme, before initiation of chemotherapy for certain malignancies when risk for TLS is considered high. Despite these guidelines, the role of rasburicase in preventing AKI remains controversial after inconclusive results in a meta-analysis. The causative relationship between uric acid and AKI in TLS is based on a mechanism of tubular obstruction. There are also mechanisms by which uric acid may cause AKI without tubular obstruction related to acute hyperuricemic nephropathy. Further characterization of the role of uric acid in causing AKI in patients without tubular obstruction may identify new mechanisms of injury and offer insight into new treatment strategies.

Co-existence of Follicular Lymphoma in the Lymph Node with High-grade B Cell Lymphoma in the Bone Marrow of a Patient with Spontaneous Tumor Lysis Syndrome.

A significant percentage of B-cell lymphomas are characterized by bone marrow involvement (BMI) at diagnosis. In most cases, there is a concordance between the type of lymphoma present in the lymph node and the lymphoma present in the bone marrow. Herein, we presented a sixty-seven years old female patient, who was diagnosed with High-Grade B-cell Lymphoma (HGBL) in the bone marrow, while simultaneously, in the peripheral lymph node, the presence of Follicular Lymphoma (FL) was noted. The patient was presented to the hospital with spontaneous tumor lysis syndrome, a finding compatible with the aggressive course of the HGBL. To our knowledge, this is the first case of the co-existence of HGBL in the bone marrow and FL in a lymph node, which might be attributed to merely a coincidence or to the transformation of the cells in the preferable milieu of the bone marrow.

Fifteen-minute consultation: Initial management of suspected acute leukaemia by non-specialists.

Leukaemia is the most common cancer of childhood. Most children with a new diagnosis of leukaemia are clinically stable at initial presentation. However, there are a number of life-threatening complications that have to be considered and monitored for. These complications include sepsis, tumour lysis syndrome, mediastinal masses, bleeding and pain. The aim of this article is to equip the general paediatrician with a framework for managing children with suspected leukaemia, prior to transfer to the primary treatment centre. The presentation, diagnosis and definitive treatment of acute leukaemia is not in the remit of this article.

Necesidad de cambios en los planes de tratamiento de los pacientes con cáncer / Need for changes in the treatment plans of patients with cancer

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Tumour lysis syndrome. / Síndrome de lisis tumoral.

Tumour lysis syndrome (TLS) is a life-threatening emergency characterised by a massive cytolysis with the release of intracellular electrolytes, nucleic acids, and metabolites into the circulation. TLS comprises laboratory derangements (hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia) responsible for acute kidney injury. In patients with hematologic malignancies after cytotoxic therapy or spontaneously and also in advanced solid tumours. Assessment of disease specific risk level for TLS in patients receiving anti-tumoural therapy is essential for early diagnosis. Prophylaxis is the mainstay of management of TLS. It is important to routinely initiate a risk-adapted prophylactic strategy to correct metabolic alterations and preserve renal function. High and intermediate risk patients and patients with established TLS should be managed with multidisciplinary medical care in a hospital unit to receive monitoring and medical care. Renal replacement therapy should be considered in patients with refractory TLS.

Opioid toxicity with underlying tumour lysis syndrome in a patient with CMML: a diagnostic and therapeutic challenge.

Use of strong opioids like morphine as analgesics for painful conditions in haematological malignancies is a challenging task. We report a unique case of chronic myelomonocytic leukaemia presenting with opioid toxicity overlapping with tumour lysis syndrome. The patient was on hydroxyurea-based chemotherapy for the primary disease. She was receiving oral morphine for abdominal pain due to splenomegaly. She was brought to the emergency in unresponsive state with pinpoint pupils. Opioid overdose leading to unconsciousness was suspected as the first diagnosis. Further workup revealed a final diagnosis of tumour lysis syndrome overlapping with opioid overdose. The patient was ventilated and started on naloxone infusion, and supportive measures for managing tumour lysis were added. The patient gradually improved and was extubated on the fifth day of ventilation. This case presents several learning points for the treating physician. Haematological malignancies have a dynamic course of disease with waxing and waning tumour burden during the course of chemotherapy. This fact should be kept in mind when prescribing strong opioids like morphine on outpatient basis to these patients. Massive tumour cell lysis during the course of chemotherapy may precipitate tumour lysis syndrome and may lead to renal dysfunction which makes the patient susceptible to morphine-related adverse effects. Pain physician should keep a watch for therapy-related adverse effects to avoid diagnostic and therapeutic dilemma associated with coexisting features of these two fatal conditions.

Rapid Fire: Tumor Lysis Syndrome.

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency, characterized by a constellation of hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia. The spectrum ranges from patients who are asymptomatic to those who go into cardiac arrest and die. Prompt recognition and initiation of treatment by emergency physicians are key, especially in the early stages of the syndrome. This case-based review presents an overview of the key points in pathophysiology, diagnosis, and management of TLS that are key to emergency physicians.

Acute Kidney Injury in Cancer Patients.

BACKGROUND: Renal complications are a relevant clinical issue in patients with cancer; conversely, cancer in patients affected by kidney diseases is a growing problem mainly due to the aging of the general population. Onco-Nephrology is a novel subspecialty addressing these issues. SUMMARY: Acute kidney injury (AKI) is an important cause of morbidity and mortality in cancer patients, and recognizes a number of different causes, which can impact, directly and indirectly, on kidney function. Furthermore, the appearance of AKI may have a tremendously negative impact on oncological treatments, often denying cancer patients active and life-prolonging treatments. Overall, patients with cancer are at risk of AKI, which could be caused by antineoplastic treatments, sepsis, metabolic disturbances, hematopoietic stem cell transplantation, primary thrombotic micro-angiopathies, and direct involvement of the kidney by hematological malignancies and also by solid cancer, in particular kidney and urothelial malignancies. Key Messages: (1) AKI is a frequent and increasing complication of cancer. (2) There is a bidirectional relationship between cancer and kidney disease, and in both cases, AKI is more likely to happen. (3) AKI in patients with cancer is associated with increased morbidity and mortality. (4) In cancer patients, a multidisciplinary approach and early intervention may reduce the incidence of AKI and its life-threatening consequences. (5) Onco-Nephrology is a growing area of nephrology that requires clinicians to have a better understanding of the renal complications of cancer including AKI.