Development of a Drosophila melanogaster based model for the assessment of cadmium and mercury mediated renal tubular toxicity

The occurrence of hypophosphataemia in paracetamol overdose suggests that nephrotoxicity is common, impaired renal tubular reabsorption of phosphate indicating renal damage. To investigate the potential nephrotoxicity of paracetamol, we studied 148 consecutive patients with paracetamol overdose. Serial clinical and biochemical measurements were made, and a fasting overnight urine collection was obtained for creatinine (Cr), phosphate and retinol-binding protein (RBP) determination. Renal threshold phosphate concentration (TmPO4/GFR) was determined from urinary parameters by an established nomogram. The degree of hypophosphataemia correlated with the severity of overdose, and with TmPO4/GFR. The median RBP/Cr ratio was higher in those patients exhibiting biochemical hepatotoxicity compared with those without hepatotoxicity, in whom median RBP/Cr was not significantly higher than controls. Within the group of patients showing biochemical hepatotoxicity, there was a correlation between log RBP/Cr and TmPO4/GFR. RBP/Cr ratio is a less sensitive marker of renal tubular toxicity than phosphaturia in these patients, and may indicate a different mechanism of toxicity.

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Hyperaminoaciduria identifies patients at risk of developing renal tubular toxicity associated with ifosfamide and platinate containing regimens

Medical and Pediatric Oncology ◽

10.1002/mpo.2950200109 ◽

1992 ◽

Vol 20 (1) ◽

pp. 42-47 ◽

Cited By ~ 33

Author(s):

Hubert N. Caron ◽

Nico Abeling ◽

Albert van Gennip ◽

Jan de Kraker ◽

P. A. Voucte

Keyword(s):

At Risk ◽

Patients At Risk ◽

Tubular Toxicity ◽

Renal Tubular

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Analgesic use of inhaled methoxyflurane

Human & Experimental Toxicology ◽

10.1177/0960327115578743 ◽

2015 ◽

Vol 35 (1) ◽

pp. 91-100 ◽

Cited By ~ 25

Author(s):

AD Dayan

Keyword(s):

Clinical Experience ◽

Renal Damage ◽

Safety Margin ◽

Tubular Damage ◽

Fluoride Ions ◽

Fluoride Level ◽

Tubular Toxicity ◽

Renal Tubular ◽

Higher Doses ◽

Analgesic Use

Methoxyflurane is a volatile, halogenated analgesic, self-administered in a controlled low dose from the Penthrox® inhaler for short-term pain relief. It was formerly used in significantly higher doses to produce anaesthesia, when it caused a specific type of dose-related renal tubular damage. The pathogenesis of the renal damage and clinical use of methoxyflurane are discussed here with evidence that a low but effective analgesic dose is not associated with the risk of renal adverse effects. The maximum dose employed to produce analgesia is limited to methoxyflurane 6 mL/day and 15 mL/week, producing a minimum alveolar concentration (MAC) of 0.59 MAC-hours. Renal damage is due to the metabolism of methoxyflurane and release of fluoride ions. Exposure of humans to methoxyflurane ≤2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, has not been associated with renal tubular toxicity. The safety margin of analgesic use of methoxyflurane in the Penthrox® inhaler is at least 2.7- to 8-fold, based on methoxyflurane MAC-hours or serum fluoride level, with clinical experience suggesting it is higher. It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity.

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