Ciclosporinの腎毒性に関する研究 第1報: Ciclosporin投与ラットにおける腎毒性について

Abstract

Ciclosporin投与ラットでは, 形態学的には近位尿細管上皮細胞の空胞変性が主であったが, dose-relatedではなかった.大量投与群では体重減少, BUNの著明な上昇を認め, catabolismの関与が大きいと考えた.血清creatinineには有意の上昇がみられず, creatinine clearanceもほとんど低下しなかった.尿中NAG活性は有意に上昇したがdose-relatedではなかった

Cyclosporin (CS) is a potent immunosuppressant that has been used in organ transplantation, but it has a serious nephrotoxic effect. To investigate its effects on renal function and structure, we carried out biochemical and morphological examinations in rats. Male Wistar rats each weighing 250 g were used. Rats were given various dose regimens (100, 50, 25 and 10 mg/kg/day) of CS orally over a 21-day period. All the rats were killed and examined on the 22nd day. Blood urea nitrogen (BUN), serum and urinary creatinine and urinary N-acetyl-s-D-glucosaminidase (NAG) were measured before administration and on the 7th, 14th and 21st day after administration. Kidneys were examined with light and electron microscopes. All rats that had received 100 mg/kg/day CS died within 12 days after a severe loss in body weight. Rats that had received 50 or 25 mg/kg/day CS had lost weight which never returned to the weight before administration. A high CS dose caused a significant elevation of BUN unaccompanied by a corresponding rise in serum creatinine. Reduction of creatinine clearance was not prominent during the experimental course. Although the urinary NAG activity was increased in high dose groups, the elevation was not related to dose. Morphological alterations were confined to the proximal tubuli and they consisted of tubular cell vacuolation and increased number of lysosomes. However, these alterations were mild and not related to the CS dose.