Cis diamminedichloroplatinum (2) : (CDDP)を中心とした多剤併用化学療法時にみられる腎障害,ことに低マグネシウム血症について

Abstract

Cis-diamminedichloroplatinum (2) (CDDP)を中心とした多剤併用化学療法を行なった非セミノーマ睾丸腫瘍5例を対象として, CDDPによる慢性腎障害を検討した.Ccrは化学療法のコースごとに一過性に低下し, 休薬期間に回復するというパターンをくり返したが, 4コース終了後2症例に非可逆的とも思われる正常の50%以下の低下が見られた.尿中β2MGはコースごとにCcrの低下に先立ち一過性に排泄増加がみられた.血清Mgレベルは5例ともコースを追うごとに低下を示したが, 尿中Mg排泄量はCDDP投与時の利尿期に一致して正常の2～3倍に増加し, Mg補給がないと10 mEq/day以下の極めて低値となった.血清Caレベルも一過性に低下したが血清Mgレベルとの相関はなく, 4コース終了時ipTHは正常であった.今回の成績から, CDDPの反復投与により用量依存的に尿細管障害が見られ, GFRの減少とβ2MG排泄増加に平行して低Mg血症が示された.しかし腎障害の軽い場合, Mgの尿中排泄量の大小に関らず, Mg補給がなくとも低Mg血症は生じにくいように思われた.血清Na, K, Caレベルの維持にはCDDP投与時に, これらの電解質液の補給を要した

Studies on renal function were made on 5 patients with nonseminomatous testicular cancer who received multiple drug chemotheraphy including CDDP. Glomerular filtration rate (GFR) decreased transiently during each course of chemotherapy and returned to the pretreatment level during the period of cessation of medication. In 2 out of 5 patients, however, an irreversible decrease to below 50 ml/min was seen after 4 courses of chemotherapy. Urinary excretion of β2 microglobulin (β2 MG) increased transiently before GFR began to decrease during each course of chemotherapy. Urinary excretion of (β2 MG persisted at a high level in patients who showed a prominent decrease in GFR. Serum magnesium levels gradually decreased. Particularly, after 4 courses of chemotherapy, hypomagnesemia was evident in 4 patients. One of them complained of neuromuscular disturbance in the four extremities. Urinary excretion of magnesium markedly increased during the diuretic phase of the period of CDDP administration and the amount of magnesium was less than 10 mEq(day without supplement of magnesium loss. However, serum magnesium levels tended to be low in the case of lowered renal function even when magnesium was supplied intravenously. Serum calcium levels decreased transiently but there was no relationship between hypocalcemia and hypomagnecemia. Serum sodium, potassium and parathyroid hormone levels remained normal through 4 courses of chemotherapy. In conclusion, intermittent adminisitration of CDDP (in total dose more than 600 mg) induced dose-dependent renal tubular damage, which caused a decrease in GFR, increase in urinary excretion of β2 MG and urinary leakage of magnesium. The severity of hypomagnesemia paralleled the impairment of renal function. Therefore, it is suggested that a subtle renal tubular dysfunction of patients receiving ODDP-treatment should be monitored regularly.