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The beneficial effect of UW solution may result from its ability to prevent tissue edema during cold storage. This study was conducted to determine which impermeant was effective in this regard during cold storage of a rat kidney in solution. Functional and morphological studies were made on a rat isolated perfused kidney (IPK) following 24 hour-cold storage in various tested solutions. Right nephrectomy was performed in 95 male rats by the method of Nishitsutsuji-Uwo et al and the kidney was perfused and stored at 4 degrees C for 24 hours as follows: glucose (194 mM) as a control, mannitol, sucrose, raffinose (140 mM in each), lactobionate (100 mM), raff + lact, hydroxyethyl starch 20, 40 (5%) with electrolyte composition essentially the same as that of Euro-Collins or UW solution. Kidneys stored for 24 hrs at 4 degrees C were perfused by the IPK apparatus. The perfusate flow rate was adjusted to maintain the renal arterial perfusion pressure at 100 mmHg. Raff, raff + lact or UW solution showed significantly higher fractional reabsorption of sodium than the control with no change in renal hemodynamics. The release of LDH into the perfusate was significantly less in raffinose than the control. Raffinose may thus be considered to function effectively as an impermeant for cold kidney preservation and molecule size would appear more important than negative charge for rat kidney preservation.

FK506, a newly developed immunosuppressive agent, has recently been used for human liver and kidney transplantation. The present study was carried out to assess the functional and morphological changes by acute or chronic administration of FK506 in heminephrectomized rats. FK506 was given intravenously at the dose of 0.384 mg/kg/hr for 90 min in acute experiment. FK506 was administered by gastric gavage at doses of 1, 2.5, 5 mg/kg for 21 days. Blood and urinary biochemistry were monitored every week. Inulin and PAH clearance studies were conducted during the infusion of FK506 for acute study, and at day 21 for chronic study. Some of the rats were treated with diltiazem (Dilt), captopril or prazosine for 21 days to prevent FK506 nephrotoxicity. Acute infusion of FK506 did not change renal and systemic hemodynamics. Creatinine clearance showed a dose dependent decrease by 10-20% in the rats with chronic administration of FK506. Inulin/PAH clearance indicated a decrease in glomerular filtration rate and renal plasma flow with an increase in renal vascular resistance. The renal histology showed vacuolization in proximal tubuli and media of smooth muscle cells of arterioles. The administration of Dilt functionally and morphologically improved renal impairment induced by FK506. In conclusion, FK506 induces a dose dependent decrease in renal function with significant histological changes in tubuli and arterioles in rat kidney. Intracellular calcium deregulation seems to be involved in FK506-induced nephrotoxicity.

In order to evaluate the direct or indirect effect of AST-120 on chronic renal failure (CRF) in rats, histological and electron microscopical examinations were performed. A total of 30 Sprague-Dawley rats (aged 11 weeks and weighing 226 to 229 gm) with CRF induced by 5/6 nephrectomy were prepared. Rats were fed by a commercial diet (CE-2, Japan Kurea) and were divided into two groups: A (16 rats) and B (14 rats). AST-120 (5% content) was only administered to group B. After two months, kidneys were removed and prepared for the histological and electron microscopical examinations. On histological examination, group A kidneys showed severe glomerular hyalinization (more than 80%) and frequent crescents, as well as tubulo-interstitial fibrosis and many protein casts. In contrast, segmental glomerular lesions were identified in group B kidneys. Tubulo-interstitium were also well preserved. Furthermore, the ultrastructural findings of group B were milder than that of group A. The preservation of renal tissue in group B revealed the beneficial effect of AST-120 on CRF rats' kidneys. In conclusion, this beneficial effect is provided by the removal of the serum toxic metabolite (uremic toxin) and the precursor substance of the toxin by orally administered AST-120.