Published: 6 March 2014

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Acute Kidney Injury - Dangerous to Continue Some Medicines

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Prescriber Update 35(1): 9–10
March 2014

There are a number of medicines that are almost exclusively renally excreted and may have toxic effects in overdose. When taking these medicines patients who experience acute kidney injury (AKI) are at risk of adverse effects. These medicines may need to be withheld until kidney function has been restored.

AKI represents a continuum of renal injury that is characterised by a rapid (hours to days) decrease in renal function with the accumulation of waste products such as creatinine and urea¹.

The causes of AKI can be divided into three categories^1,2.

1. Pre-renal injury due to a reduction in blood flow to the kidney
   Causes include (but are not limited to) diarrhoea, vomiting, diuretics, haemorrhage, trauma, sepsis, decompensated heart failure, major surgery, infection, and medicines such as NSAIDs, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
2. Intrinsic injury due to direct kidney damage
   Causes include (but are not limited to) vasculitis, glomerulonephritis, interstitial nephritis, rhabdomyolysis, malignant disease and nephrotoxic medicines such as NSAIDs, lithium and aminoglycosides
3. Post-renal injury due to a blockage to the flow of urine.
   Causes include (but are not limited to) kidney stones, prostatic hypertrophy and obstructed urinary catheter.

A number of cases have been reported in the literature in which patients experienced adverse events due to the combination of a medicine and AKI.

Dabigatran

A patient taking dabigatran experienced AKI due to dehydration after a brief gastrointestinal illness³. The patient’s creatinine increased to more than 1.5 times baseline. The AKI resulted in decreased clearance and increased plasma concentration of dabigatran as manifested by standard measures of coagulation. Dabigatran was withheld with resolution of coagulopathy over four days.

The data sheet for dabigatran states that renal function should be assessed in clinical situations when it is suspected that renal function could decline or deteriorate⁴. Treatment with dabigatran is contraindicated in severe renal impairment⁴.

Metformin

In this report for two patients, metformin related lactic acidosis symptoms emerged shortly after the patients experienced AKI⁵. In the first case, use of oral NSAIDs along with dehydration caused by persistent vomiting contributed to AKI. In the second case, fluid loss from diarrhoea probably induced AKI. Both patients were successfully treated with haemodialysis.

The data sheet states that renal insufficiency is a risk factor for systemic accumulation of metformin and consequently lactic acidosis⁶. Metformin is contraindicated in patients with creatine clearance less than 60 mL/minute⁶.

Gabapentin

An elderly lady with AKI taking prescribed gabapentin experienced serious mental status changes resulting in the need for transfer to intensive care⁷. Consciousness was restored in this patient by stopping gabapentin treatment and starting continuous venovenous haemofiltration. The data sheet recommends a dose adjustment in renal impairment⁸.

Olanzapine

An 80-year-old man was admitted to hospital with altered mental status and hypothermia. He had a recent history of gastroenteritis with dehydration resulting in AKI⁹. The patient was taking, among other medicines, olanzapine, to which the authors attributed the hypothermia.

The data sheet advises that olanzapine is used with caution in those with severe renal impairment¹⁰. Olanzapine is not removed by haemodialysis¹⁰.

These cases illustrate the need to consider dose adjustment of renally excreted medicines in patients with established AKI or patients who are developing AKI.

References

1. Bellamo R, Kellum JA, Ronco C. 2012. Acute kidney injury. Lancet 380: 756–766.
2. Best Practice Advocacy Centre. 2012. Acute on chronic kidney disease: Prevention, diagnosis, management and referral in primary care. Best Practice Journal 46: 10–15.
3. Fountzilas C, George J, Levine R. 2013. Dabigatran overdose secondary to acute kidney injury and amiodarone use. New Zealand Medical Journal 126: 110–112.
4. Boehringer Ingelheim (NZ) Ltd. 2013. Pradaxa Data Sheet 3 May 2013. URL: www.medsafe.govt.nz/profs/Datasheet/p/Pradaxacap.pdf (accessed 10 February 2014).
5. Devetzis V, Passadakis P, Panagoutsos S, et al. 2011. Metformin related lactic acidosis in patients with acute kidney injury. International Urology and Nephrology 43: 1243–1248.
6. Apotex NZ Ltd. 2011. Metformin Data Sheet 29 July 2011. URL: www.medsafe.govt.nz/profs/Datasheet/m/Metformintab.pd (accessed 10 February 2014).
7. Miller A, Price G. 2009. Gabapentin toxicity in renal failure: The importance of dose adjustment. Pain Medicine 10(1): 190–192.
8. Pfizer New Zealand Ltd. 2013. Neurontin Data Sheet 5 November 2013. URL: www.medsafe.govt.nz/profs/Datasheet/n/Neurontincaptab.pdf (accessed 10 February 2014).
9. Kansagra A, Patel S, Wilcox SR. 2013. Prolonged hypothermia due to olanzapine in the setting of renal failure: a case report and review of the literature. Therapeutic Advances in Psychopharmacology 3(6): 335–339.
10. Eli Lilly and Company (NZ) Limited. 2013. Zyprexa Data Sheet 31 January 2014. URL: www.medsafe.govt.nz/profs/datasheet/z/ZyprexatabZyprexazydiswafer.pdf (accessed 10 February 2014).