Severe hypophosphataemia in paracetamol-induced oliguric renal failure

Kai-Uwe Eckardt, Carsten Willam and Ulrich Frei

Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow-Klinikum, Humboldt-University, Berlin, Germany

Correspondence and offprint requests to: K.-U. Eckardt MD, Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany.

Keywords: hypophosphataemia; paracetamol; renal failure



   Introduction
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 Introduction
 Case
 Discussion
 References
 
Since the first reports of paracetamol overdose, acute renal failure has often been noted as a complication of fulminant hepatic failure [1]. A similar frequency of renal impairment in paracetamol intoxications and other causes of acute liver damage suggested that this association is not due to a specific nephrotoxic effect of paracetamol [2]. Subsequently, however, retrospective analysis of two large patient series revealed that approximately 1% of patients admitted after paracetamol overdose develop acute renal failure in the absence of fulminant liver damage [3,4]. In addition, single cases were reported in whom renal failure occurred in the absence of any clinical or biochemical evidence of liver damage [4,5].

Hypophosphataemia is another recognized feature of paracetamol poisoning. Its incidence and severity correlate with the extent of hepatic damage, but it was also found in the absence of clinical or biochemical evidence of liver toxicity [6]. Jones et al. [6] concluded, from a significant correlation between the serum phosphate concentration and renal phosphate threshold concentration, that the hypophosphataemia associated with paracetamol intoxication is due to phosphaturia rather than intracellular redistribution. Here we report a case of severe hypophosphataemia in a patient with paracetamol intoxication, who was oliguric, which argues strongly against renal phosphate loss as the underlying mechanism.



   Case
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 Introduction
 Case
 Discussion
 References
 
A 33-year-old woman was admitted to a community hospital 24 h after ingestion of 25 g paracetamol in a suicide attempt. Her previous medical history was unremarkable. The plasma paracetamol concentration on admission was 5.2 mg/l and her transaminases were moderately elevated (Table 1Go). Treatment with n-acetyl cysteine was started immediately. The following day she was transferred to a transplant unit because of a significant further rise in her liver enzymes, but hepatic function improved subsequently. She developed oliguria and on the 3rd day after intoxication her serum creatinine had risen from 1.0 to 1.3 mg/dl and increased further thereafter (Table 1Go). Urinary sodium was >100 mmol/l and the urine to plasma creatinine ratio <10. Her plasma phosphate concentration fell to a minimum of 0.1 mmol/l on day 5. She was dialysed thrice before her renal function recovered gradually.


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Table 1. Laboratory and clinical indices in a 35-year-old woman, who ingested 25 g paracetamol on day 1
 


   Discussion
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 Introduction
 Case
 Discussion
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Paracetamol overdose is thought to cause renal tubular damage through similar mechanisms that effect liver cells. These mechanisms include the generation of highly reactive arylating metabolites in situ which can be trapped by reduced glutathione and become toxic only after depletion of glutathione stores [7]. Urine biochemistry in the reported case is in accordance with acute tubular necrosis rather than prerenal or hepatorenal failure [8]. Others have reported that renal failure is most evident 1 week after paracetamol ingestion compared with 2–4 days for the liver damage [3]. The present case suggests that there is no significant time difference between the injury to both organs, although the liver recovers more quickly.

Unfortunately, in the acute emergency plasma PTH and 1,25 (OH)2D3 were not measured and urinary phosphate excretion was not determined, but it appears highly unlikely that in the presence of oliguria sufficient phosphate is excreted in the urine to explain the marked decrease in the serum phosphate level. The patient did not receive glucose infusions, beta-receptor agonists, or intravenous calcium, had no respiratory alkalosis and denied chronic alcohol abuse, which may all trigger hypophosphataemia [9]. She did not develop muscle weakness or other symptoms possibly related to hypophosphataemia and there was also no increase in creatinine kinase. No phosphate replacement was provided, and thus the sudden increase between days 5 and 6 also indicates redistribution rather than a preceding loss of phosphate.



   References
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 Introduction
 Case
 Discussion
 References
 

  1. Davidson DGD, Eastham WN. Acute liver necrosis following overdose of paracetamol. Br Med J 1966; 2: 497–499
  2. Wilkinson SP, Moodie H, Arroyo VA, Williams R. Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage. J Clin Pathol 1977; 30: 141–143[Abstract]
  3. Cobden I, Record CO, Ward MK, Kerr DNS. Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Br Med J 1982; 284: 21–22[ISI][Medline]
  4. Prescott LF, Proudfoot AT, Gregeen RJ. Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Br Med J 1982; 284: 421–422[Medline]
  5. Kher K, Makker S. Acute renal failure due to acetaminophen ingestion without concurrent hepatotoxicity. Am J Med 1997 82: 1280–1281
  6. Jones AF, Harvey JM, Vale JA. Hypophosphataemia and phosphaturia in paracetamol poisoning. Lancet 1989; 2: 608–609[Medline]
  7. Mitchell JR, McMurtry RJ, Statham CN, Nelson SD. Molecular basis for several drug-induced nephropathies. Am J Med 1977; 62: 518–526[ISI][Medline]
  8. Eckardt K-U. Renal failure in liver disease. Intensive Care Med 1999; 25: 5–14[ISI][Medline]
  9. Peppers M, Geheb M, Desai T. Hypophosphatemia and hyperphosphatemia. Crit Care Clin 1991; 7: 201–214[ISI][Medline]
Received for publication: 5. 3.99
Accepted in revised form: 7. 4.99





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