Webb D E, Austin H A, Belldegrun A, Vaughan E, Linehan W M, Rosenberg S A
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
Clin Nephrol. 1988 Sep;30(3):141-5.
The systemic administration of recombinant interleukin-2 (IL-2) either alone or in combination with lymphokine activated killer cells is a new approach to the immunotherapy of metastatic cancer in man. Renal toxicity is often a dose-limiting side effect of IL-2 administration. This prospective study of 17 consecutive patients receiving parenteral high dose IL-2 documents a reversible syndrome of hypotension, oliguria, fluid retention, azotemia and very low urinary excretion of sodium (median FeNa of 0.04%). The median nadir urinary uric acid to urinary creatinine ratio during IL-2 therapy was 0.2. This IL-2 regimen induces a reversible renal hypoperfusion syndrome (pre-renal azotemia) without evidence of acute uric acid nephropathy. Hypophosphatemia [median serum phosphorus of 1.9 mg/dl (0.61 mmol/l)] prompted further study of tubular function. Urinary excretions of phosphorus, calcium and magnesium were very low. Arterial blood gases revealed hyperventilation without alkalemia. The hypophosphatemia probably reflects increased utilization of inorganic phosphorus by rapidly proliferating lymphoid cells.
单独或与淋巴因子激活的杀伤细胞联合全身给予重组白细胞介素-2(IL-2)是人类转移性癌免疫治疗的一种新方法。肾毒性常常是IL-2给药的剂量限制性副作用。这项对17例连续接受胃肠外高剂量IL-2治疗患者的前瞻性研究记录了一种可逆性综合征,包括低血压、少尿、液体潴留、氮质血症以及极低的尿钠排泄(尿钠排泄分数中位数为0.04%)。IL-2治疗期间尿尿酸与尿肌酐比值的中位数最低点为0.2。这种IL-2治疗方案可诱发可逆性肾灌注不足综合征(肾前性氮质血症),而无急性尿酸肾病的证据。低磷血症[血清磷中位数为1.9mg/dl(0.61mmol/l)]促使对肾小管功能进行进一步研究。磷、钙和镁的尿排泄量非常低。动脉血气显示过度通气但无碱血症。低磷血症可能反映了快速增殖的淋巴细胞对无机磷利用的增加。