Yoshiteru Kaneko

Reversibility of adenine-induced renal failure in rats

AbstractBackground. A renal failure model prepared from rats fed on an adenine diet provides valuable information about the pathomechanism of various complications associated with a persistent uremic state. To establish an animal experimental model in which the animals survive in a persistent uremic state, it is essential to settle a point of no return, i.e., an irreversible point. We investigated an irreversible point using the rat renal failure model induced by adenine treatment. Methods. Rats were fed on a diet containing 0.75% adenine for 2, 4, or 6 weeks, and they were then fed an adenine-free diet for an additional 4 weeks to evaluate the degree of recovery from renal dysfunction. Results. The rats fed on the adenine diet for 2 weeks showed a decrease in mean serum creatinine(s-Cr) from 1.8 mg/dl before to 0.7 mg/dl after the observation period, with mild anemia. The rats fed on the adenine diet for 4 weeks showed persistent renal dysfunction. Although the mean s-Cr decreased from 2.7 to 2.0 mg/dl, it continued to be higher than the normal range, and the anemia worsened. In the rats fed on the adenine diet for 6 weeks, the mean s-Cr increased from 3.4 to 3.6 mg/dl. Hypoproteinemia was also observed and some animals died. Conclusion. Based on the above results, it was concluded that to prepare a model of chronic renal failure in rats compatible to chronic renal failure seen clinically, the administration of a 0.75% adenine diet for 4 weeks is most appropriate.

Branched chain amino acid in adenine-induced uremic rats treated with rHuEPO

AbstractBackground. It is well known that chronic renal failure shows an abnormal amino acid profile characterized by a decrease in branched chain amino acid (BCAA). Methods. To investigate the change in BCAA with uremia and the effect of recombinant human erythropoietin (rHuEPO) on BCAA level, we measured the plasma and muscle levels of BCAA in adenine-induced renal anemia in Wistar rats. Results. A significant correlation was found between plasma and muscle tissue levels of BCAA. Further, not only the plasma level but the muscle level of each BCAA showed an inverse correlation with the serum creatinine value. Both plasma and muscle BCAA levels showed, in addition, significant recovery after rHuEPO treatment. Conclusions. Taking these results into account, we conclude that the decrease in BCAA is a clinicopathological feature essentially associated with uremia (i.e., it is not an epiphenomenon), and that BCAA levels could be recovered by rHuEPO treatment. However, the pathological mechanism by which BCAA level is decreased in the uremic state and is recovered after rHuEPO treatment remains to be elucidated.

The optimum concentration of dialysate Ca++ using citrate

クエン酸透析において, クエン酸中毒のriskを除き, かつ十分な抗凝固効果を得るためには, 回路内至適クエン酸濃度は1.0-1.5mM必要であり, この場合回路内Ca++濃度は0.6-0.8mMであることを, すでに確認し報告したが, 今回, 回路内至適クエン酸濃度1.0-1.5mMでの透析液至適Ca++濃度を検討した.ホロファイバー型ダイアライザーを用い, 回路流量200ml/min, 透析液流量500ml/min, 回路内Ca++濃度を一定に保つために2% CaCl2液を注入し, 回路リザーバー容量を10lに設定した再循環式閉鎖型回路を作製した. 動脈側よりチトラール30ml/hrを注入し, 回路作動後15分, 30分, 60分, 90分に, リザーバー出口, 動脈側, 静脈側の3点で試料採取を行った. Ca++濃度0mM, 0.5mM, 1.0mM, 1.5mMの透析液を採取し, 比較検討した.透析液Ca++濃度0mM, 0.5mMの場合, 動脈側, 静脈側ともに, 50%前後の回路内Ca++濃度の抑制が見られた. 一方, 透析液Ca++濃度1.0mM, 1.5mMでは動脈側で約50%の回路内Ca++濃度の抑制を得るが, 静脈側では殆ど抑制効果は認めなかった. したがって, クエン酸透析における至適透析液Ca++濃度は0.5mMと考える.