No abstract

No abstract

The early alterations at the level of the proximal tubule of the human kidney caused by the three most currently used aminoglycosides, gentamicin, tobramycin, and amikacin, were studied. A prospective, randomized, and comparative approach using multidisciplinary methods was used. The patients received either no treatment or one of the three aminoglycosides at a therapeutic dose for 4 days preceding nephrectomy for neoplasia partly involving one kidney. The three aminoglycosides studied induce an early lysosomal phospholipidosis. Gentamicin and tobramycin cannot be distinguished on the basis of drug tissue accumulation, lysosomal overloading, or effect on lysosomal phospholipase A1. Amikacin induces significantly lower lysosomal overloading and no loss of phospholipase A1 activity.

The recovery from gentamicin-induced phospholipidosis in the rat kidney cortex was characterized both morphologically and biochemically after a single 12-hr drug infusion. Total dosages administered were 10, 60, or 140 mg/kg, achieving constant serum concentrations of 3, 11, and 27 micrograms/ml, respectively. At the end of the 12-hr infusion, the cortical drug concentrations corresponding to the three dosages were 124, 450, and 993 micrograms/g of wet tissue. At the low dose (10 mg/kg), myeloid bodies were seen inside lysosomes of proximal tubular cells, along with a modest decrease of lysosomal sphingomyelinase activity. The cortical drug level declined steadily following first-order kinetics along with a disappearance of myeloid bodies and return of sphingomyelinase activity to control levels. At the high dose (140 mg/kg), we observed a sustained loss of sphingomyelinase activity (37% of controls), a subsequent increase of phospholipid concentration in the kidney cortex (up to 117% of controls 2 days after) and a prominent accumulation of myeloid bodies inside the lysosomes of proximal tubular cells (up to 4% of cell volume). Tubular regeneration and interstitial infiltration became detectable by histology and the increase of DNA synthesis as from day 1, along with an apparent reduction of the phospholipidosis at days 3 and 4. Drug cortical concentrations showed a sharp decline 2 days after infusion. An intermediate behavior was observed at 60 mg/kg. It is concluded that the proximal tubular cells behave in a fundamentally different way after gentamicin loading with low and high doses. At the low dose there is a regression of the drug-induced changes in the absence of any sign of necrosis-regeneration. Above a threshold in cortical drug concentration there is further development of the alterations leading to cell death-regeneration.

No abstract

No abstract

We r e p o r t on a p a t i e n t t r e a t e d w i t h hemoperfusionhemodialysi s (HP-HD) f o r severe paraquat p o i soni ng. This procedure was adopted since t h e combination o f adsorption and d i a l y s i s may improve o v e r a l l drug removal. On admission blood paraquat was 15.8 vg/ml. He received conventional treatment and combined HP-HD which s t a r t e d w i t h i n 3 hours a f t e r i n g e s t i o n o f t h e chemical and l a s t e d 5 hours. Blood samples were obtained d u r i n g and a f t e r HP-HD. before t h e charcoal column, between t h e charcoal column and t h e a r t i f i c i a l kidney and a f t e r t h e a r t i f i c i a l kidney. Blood clearances o f paraquat were 116 , + 32 ml/min (n=6) f o r t h e charcoal column (HP), 90 2 54 ml/min (n=6) f o r the a r t i f i c i a l kidney (HD) and 151 & 37 ml/min (n=6) f o r t h e combined systems (HP-HD). A f t e r HP-HD a l i m i t e d rebound o f blood paraquat l e v e l was seen.developed, and the p a t i e n t died a f t e r 5 days. Tissue paraquat l e v e l s (vg/g wet t i s s u e ) were: s k e l e t a l muscle 9.4, pancreas 6.0, p r o s t a t e 5.6, t h y r o i d 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, h e a r t 2.8, l i v e r 2.3, stomach and t e s t i s below 1.0.The samples d u r i n g HP-HD were takenOne day a f t e r admission renal and hepatic f a i l u r e had 117 Copyright 0 1985 by Marcel Dekker, Inc. 073 1-3810/85/2302-0117$3.50/0 Clinical Toxicology Downloaded from informahealthcare.com by University New South Wales on 08/23/15 For personal use only.

No abstract