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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR  
Year : 2016  |  Volume : 27  |  Issue : 6  |  Page : 1276-1279
Diethylene glycol poisoning-induced acute kidney injury


Institute of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India

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Date of Web Publication28-Nov-2016
 

How to cite this article:
Gopalakrishnan N, Kamarajan M, Balasubramaniyan T, Sakthirajan R, Dhanapriya J, Dineshkumar T. Diethylene glycol poisoning-induced acute kidney injury. Saudi J Kidney Dis Transpl 2016;27:1276-9

How to cite this URL:
Gopalakrishnan N, Kamarajan M, Balasubramaniyan T, Sakthirajan R, Dhanapriya J, Dineshkumar T. Diethylene glycol poisoning-induced acute kidney injury. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Jan 22];27:1276-9. Available from: http://www.sjkdt.org/text.asp?2016/27/6/1276/194692
To the Editor,

Diethylene glycol (DEG) is present in brake oil and is used as an illegal adulterant in ethanol spirits or in medications. [1] We report a case of brake oil poisoning who presented as acute abdomen and later developed dialysisrequiring renal failure, hypertension, deafness, and multiple neurological deficits. Renal biopsy revealed severe acute tubulointerstitial nephritis with tubular necrosis without deposition of oxalate crystals.

A 14-year-old boy was admitted to the emergency department with acute abdominal pain and vomiting. He underwent emergency appendectomy after a provisional diagnosis of acute appendicitis. As he was found to have a severe renal failure, he was referred to nephrology department two days after surgery. On admission to our ward, he was drowsy, hypertensive [blood pressure (BP): 150/90 mm Hg], and oliguric. He had generalized tonic-clonic seizures. Subsequently, he developed involuntary movements and flaccid muscle weakness of all four limbs and gross impairment of hearing.

Investigations: Urine analysis showed 1 + proteinuria, 1-2 red blood cells/hpf, and no crystals. Blood biochemistry revealed serum creatinine 7.3 mg/dL, amylase 481 IU/L, and lipase 1480 IU/L. Arterial blood gas analysis revealed pH of 7.21, HCO [3] 12 mmol/L, base excess 10 mmol/L, and anion gap of 21. Ultrasonogram showed bilaterally enlarged kidneys. Computerized tomography of the brain was normal. Audiogram revealed bilateral sensorineural hearing loss.

He was given supportive treatment, antihypertensives, and initiated on hemodialysis (HD). On further probing, he revealed accidental consumption of 100 mL of brake fluid mistaking it for a beverage (Castrol, DOT3 shown in [Figure 1]. Renal biopsy was done on 3 rd week of admission which showed severe acute tubulointerstitial nephritis with tubular necrosis without deposition of oxalate crystals [Figure 2]. He was dialysis dependent for four weeks. His BP normalized after two months, and serum creatinine reached nadir of 1.1 mg/dL in four months. His hearing also improved significantly.
Figure 1: Brake fluid the patient alleged to consume.

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Figure 2: Renal biopsy showing acute tubular injury with dense inflammatory infiltrates in the interstitium (H and E).

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DEG is a cheap, clear, odorless substance, and of sweet taste making it an ideal adulterant in ethanol and medications. Most reported cases of DEG toxicity in children occurred when it is used as a solvent in medications. Due to its late recognition, its ingestion causes about 90% mortality. [1],[2] The toxic dose of DEG has been estimated to be 0.14 mg/kg and the lethal dose is 1-1.63 g/kg. [3] Once ingested, it is rapidly absorbed from the gut.

DEG is not metabolized to ethylene glycol though it consists of two linked ethylene glycol molecules. The metabolism is different for both and their toxicities also differ. Around 50-70% of DEG is oxidized by alcohol dehydrogenase (ADH) to 2-hydroxyethoxy acetaldehyde and then by aldehyde dehydrogenase (ALDH) to 2-hydroxyethoxy acetic acid (HEAA) as shown in [Figure 3]. This is why calcium oxalate crystals, typical of ethylene glycol intoxication, are not found after DEG poisoning. Metabolic acidosis and organ dysfunction are postulated to result from the generation of HEAA which is excreted primarily through the kidneys. The mechanism by which HEAA produces cellular dysfunction is said to be membrane destabilization and intracellular accumulation of osmotically active particles causing transcellular shifts. [4]
Figure 3: Metabolism of diethylene glycol.

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The clinical features of DEG intoxication can be divided into three phases. [5] The first phase typically involves gastrointestinal side effects such as nausea, vomiting, abdominal pain, and diarrhea. Patient may have high or normal anion gap metabolic acidosis in the first phase. Progression to the second phase depends on the amount of ingestion. The second phase occurs 1-3 days following exposure, the hallmark of which is acute renal failure. Acute tubular necrosis is the usual biopsy picture. Cardiac dysrhythmias, tachycardia, hypertension, pulmonary edema, and pancreatitis have also been reported. The coexistent hepatic damage is manifested by transaminase level elevation.

The third phase occurs 1-2 weeks after the ingestion. Neurological complications dominate in this period. The degree of kidney injury can predict the extent of neurological dysfunction. Peripheral neuropathy is a common occurrence, and cranial nerve abnormalities including bilateral facial nerve palsy and bulbar palsy have been reported. Widespread denervations of limb muscle have been demonstrated. Patient may become quadriparetic and unresponsive, and the clinical course during this phase is unpredictable.

Renal damage in DEG poisoning is due to proximal tubular necrosis. Severe vacuolation and swelling of epithelial cells cause obstruction of the lumen. The renal toxicity is due to HEAA and diglycolic acid. Diglycolic acid after glomerular filtration is transported into the proximal tubular cells by apical sodium dicarboxylate transporters-1 or organic anion transporters, [6] where it inhibits citric acid cycle enzyme and causes cell death by blocking adenosine triphosphate production.

Measurement of serum DEG concentration by gas chromatography is the gold standard for diagnosis. [4],[7] As this test is not widely available, diagnosis of DEG poisoning is often presumed on history and laboratory abnormalities. Metabolic acidosis is mild to severe and usually occurs 24-h post-ingestion. Elevation of serum amylase and liver enzymes suggest pancreatic and hepatic injury, respectively.

Decontamination with activated charcoal is recommended only when the patient presents within 30 min of ingestion. DEG and its metabolites have low volume of distribution (0.5 L/kg) and protein binding, and 50%-70% of it is excreted by the kidneys, and it is easily removed by dialysis. [8] Administration of inhibitors of ADH and ALDH (fomepizole/ethanol) can prevent the production of HEAA. Dialysis with or without fomepizole or ethanol has been used in the treatment of most patients.

Most of the case reports of DEG poisoning were epidemic outbreaks due to contamination of pharmaceutical products. In the largest ever case series of 109 children with acute renal failure published from Haiti, [3],[8] glycerin used in acetaminophen syrup was found to be contaminated with 24% DEG which caused 98% mortality. Two similar case series [9],[10] from India reported high case fatality. Hari et al [10] have reported 11 fatal cases of DEG poisoning with acute renal failure following administration of paracetamol syrup where DEG was substituted for glycerin as a solvent. Devoti et al recently described a case of DEG poisoning through transcutaneous absorption. [6] After DEG poisoning, death occurs in more than twothirds of patients. Most of the patients with renal failure who survive remain dialysisdependent.

Our patient had most of these clinical features namely, abdominal pain, vomiting, acute tubular necrosis, pancreatic injury, quadriparesis, and transient VIII nerve involvement which improved over two weeks. He received intensive HD and supportive treatment. His renal failure improved completely after four months, and he has normal renal function till the last follow-up.

DEG intoxication should be suspected in the presence of high anion gap acidosis with multisystem involvement. Early recognition and initiation of appropriate management are the cornerstone of the management.

Conflict of interest: None declared.

 
   References Top

1.
Kraut JA, Kurtz I. Toxic alcohol ingestions: Clinical features, diagnosis, and management. Clin J Am Soc Nephrol 2008;3:208-25.  Back to cited text no. 1
    
2.
Sharma N, Jain S. Toxicity of brake oil. Emerg Med J 2002;19:267-8.  Back to cited text no. 2
    
3.
Woolf AD. The Haitian diethylene glycol poisoning tragedy: A dark wood revisited. JAMA 1998;279:1215-6.  Back to cited text no. 3
    
4.
Schep LJ, Slaughter RJ, Temple WA, Beasley DM. Diethylene glycol poisoning. Clin Toxicol (Phila) 2009;47:525-35.  Back to cited text no. 4
    
5.
Alfred S, Coleman P, Harris D, Wigmore T, Stachowski E, Graudins A. Delayed neurologic sequelae resulting from epidemic diethylene glycol poisoning. Clin Toxicol (Phila) 2005; 43:155-9.  Back to cited text no. 5
    
6.
Devoti E, Marta E, Belotti E, et al. Diethylene glycol poisoning from transcutaneous absorption. Am J Kidney Dis 2015;65:603-6.  Back to cited text no. 6
    
7.
Hanif M, Mobarak MR, Ronan A, Rahman D, Donovan JJ Jr., Bennish ML. Fatal renal failure caused by diethylene glycol in paracetamol elixir: The Bangladesh epidemic. BMJ 1995; 311:88-91.  Back to cited text no. 7
    
8.
O'Brien KL, Selanikio JD, Hecdivert C, et al. Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. Acute Renal Failure Investigation Team. JAMA 1998;279:1175-80.  Back to cited text no. 8
    
9.
Singh J, Dutta AK, Khare S, et al. Diethylene glycol poisoning in Gurgaon, India, 1998. Bull World Health Organ 2001;79:88-95.  Back to cited text no. 9
    
10.
Hari P, Jain Y, Kabra SK. Fatal encephalopathy and renal failure caused by diethylene glycol poisoning. J Trop Pediatr 2006;52:442-4.  Back to cited text no. 10
    

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Correspondence Address:
Jeyachandran Dhanapriya
Institute of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu
India
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DOI: 10.4103/1319-2442.194692

PMID: 27900981

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  [Figure 1], [Figure 2], [Figure 3]



 

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