Tiu Ramon V, Mountantonakis Stavros E, Dunbar Andrew J, Schreiber Martin J
Internal Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Semin Thromb Hemost. 2007 Jun;33(4):397-407. doi: 10.1055/s-2007-976175.
Tumor lysis syndrome (TLS) is an important metabolic disorder frequently encountered in the management of a variety of cancers including lymphoma, leukemia, and neuroblastoma. Delayed recognition can result in a variety of biochemical abnormalities resulting in life-threatening complications such as renal failure, arrhythmias, and seizures. Identification of high-risk patients and early recognition of the syndrome is crucial in the early institution of appropriate prophylaxis and treatment. Recent advances in the understanding of urate metabolism, development of new urate-lowering drugs, and the application of biomarkers, calculation methods, and prognostic models to identify high-risk patients will pave the way in improving the management of TLS. We included in this review the new information regarding the urate transporters URAT-1, organic anion transporter 1/3, and MRP4; the urate elimination pathway; a comparison of the old- (allopurinol, native uricase) and new- (febuxostat, Y-700, PEG-uricase, rasburicase) generation urate-lowering agents; and application of new biomarkers (cystatin-C, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1), estimated glomerular filtration rate and calculation methods (modification of diet in renal disease and prognostic model (Penn Predictive Score of Tumor Lysis Syndrome) in the identification of high-risk patients, and alternative unexplored mechanisms (asymmetric dimethylarginine and adenosine) to explain renal injury related to TLS.
肿瘤溶解综合征(TLS)是一种重要的代谢紊乱,在包括淋巴瘤、白血病和神经母细胞瘤在内的多种癌症的治疗中经常遇到。识别延迟可导致多种生化异常,进而引发危及生命的并发症,如肾衰竭、心律失常和癫痫发作。识别高危患者并早期识别该综合征对于早期实施适当的预防和治疗至关重要。在尿酸代谢认识方面的最新进展、新型降尿酸药物的研发以及用于识别高危患者的生物标志物、计算方法和预后模型的应用,将为改善TLS的管理铺平道路。我们在本综述中纳入了关于尿酸转运蛋白URAT-1、有机阴离子转运体1/3和MRP4的新信息;尿酸清除途径;旧一代(别嘌醇、天然尿酸酶)和新一代(非布司他、Y-700、聚乙二醇化尿酸酶、拉布立酶)降尿酸药物的比较;以及新生物标志物(胱抑素C、中性粒细胞明胶酶相关脂质运载蛋白、肾损伤分子1)、估计肾小球滤过率和计算方法(肾脏病饮食改良)和预后模型(肿瘤溶解综合征宾夕法尼亚预测评分)在识别高危患者中的应用,以及用于解释与TLS相关的肾损伤的其他未探索机制(不对称二甲基精氨酸和腺苷)。