Renal Consequences of Long-Term, Low-Dose Intentional Ingestion of Ethylene Glycol

Abstract

Acute renal failure can result from a wide variety of causes. When the cause of acute renal failure is unclear, the history, physical examination, and laboratory findings are crucial to help establish the cause. However, the cause of acute renal failure may remain unclear even after gathering this information. In this report, we describe a case of acute chronic renal failure in which the cause of acute renal failure was not determined until a kidney biopsy was performed, which revealed calcium oxalate crystals in the renal parenchyma, a finding pathognomonic for ethylene glycol ingestion.

Keyword:

• ethylene glycol

INTRODUCTION

A 43-year-old woman was brought to our emergency department (ED) by her husband after he witnessed her having a tonic-clonic seizure lasting one minute, followed by ten minutes of unresponsiveness, and then confusion and slurred speech. Notably, the night prior to the episode, the patient had not been feeling well, complained of weakness, and had slurred speech. The patient's past medical history included type 2 diabetes mellitus, hypertension, Hashimoto's thyroiditis, chronic renal insufficiency (baseline creatinine 1.7–2.3 mg/dL), and depression. She had two prior suicide attempts by ingestion of ethylene glycol. She was taking several medicines that lower seizure threshold, including quetiapine, bupropion, and citalopram; the dose of citalopram was recently doubled. In the ED, the patient's vital signs were normal, but she was confused and disoriented to person, place, and time. She moved all of her extremities spontaneously and her pupils were equal, round, and reactive to light. Blood work revealed a sodium of 131 mmol/L (reference range 135–145 mmol/L), potassium 6.3 mmol/L (reference range 3.6–5.2 mmol/L), chloride 102 (reference range 100–108 mmol/L), bicarbonate 7 mmol/L (reference range 22–29 mmol/L), creatinine 4.7 mg/dL (reference range 0.6–1.1 mg/dL), anion gap 22 (reference range 7–15), serum osmolality 309 mOsm/kg (reference range 275–295 mOsm/kg), lactate 9.5 mmol/L (reference range 0.6–2.3 mmol/L), and a pH of 7.26 (reference range 7.35–7.45). Urinalysis, serum and urine drug screens, chest x-ray, ultrasonography of the kidneys, and computed tomography of the head were unremarkable. Because of her altered mental state, metabolic acidosis, and acute chronic renal failure, she was admitted to the intensive care unit (ICU).

After the patient's second day in the hospital, her lactate level normalized and her metabolic acidosis resolved (see Table 1 for daily laboratory values). The metabolic acidosis was thought to be due to lactic acidosis caused by the seizure. She had no further seizures in the hospital, and an electroencephalogram obtained the day after admission was unremarkable. Three days after admission, she was transferred from the ICU to a regular hospital bed. However, she was oliguric. Notably, her serum creatinine increased from 4.7 mg/dL on admission to 8.9 mg/dL on her third day in the hospital. Hemodialysis was started. Because the etiology of the patient's renal failure was unclear, a kidney biopsy was obtained.

Table 1 Results of laboratory studies in a 43-year-old woman with acute chronic renal failure

Hospital Day #	1	2	3	4	5	6	7
Creatinine (mg/dL)	4.7	5.7	8.9	8.8	10.6	9.5	11.4
BUN (mg/dL)	37	42	57	52	64	52	63
Bicarbonate	7	15	13	19	19	25	22
pH	7.26	7.29
Lactate (mmol/L)	9.5	1.3

The kidney biopsy showed an acute tubulointerstitial process superimposed on chronic parenchymal damage (see Figure 1a). Calcium oxalate crystals were seen within non-scarred areas of the parenchyma, a finding consistent with ethylene glycol ingestion (see Figure 1b). The patient was informed of the biopsy results and subsequently admitted to ingesting 1–2 tablespoons of antifreeze 2–3 days per week during the prior six weeks. However, she stopped ingesting antifreeze 3–4 days prior to admission to the hospital. The patient was diagnosed with renal failure due to long-term, low-dose ingestion of ethylene glycol and was transferred to our psychiatric hospital for management of underlying depression.

Figure 1. Kidney biopsy from a 43-year-old woman with acute chronic renal failure. The specimen is examined using an H&E stain at a magnification of 100 × the original size. In Figure 1a, the specimen is examined under bright-field microscopy, showing an acute tubulointerstitial process superimposed on chronic parenchymal damage. There is diffuse acute tubular injury with interstitial edema as well as substantial background fibrosis (40–50%). An active inflammatory infiltrate is seen; however, there are no granulomas and eosinophils are not prominent. In Figure 1b, the specimen is examined under plane-polarized illumination. White birefringence from calcium oxalate type crystals are present within nonscarred areas, suggesting recent deposition. The history of recent ethylene glycol ingestion is the likely etiology.

During her psychiatric hospitalization, citalopram was restarted at pre-hospital doses, and bupropion, quetiapine, and hydrochlorothiazide were held. She began attending individual outpatient psychotherapy and a dialectical behavioral therapy group for treatment of her mood disorder.

The patient remained dialysis-dependent after her hospitalization. Indeed, nine weeks after the patient's original admission, blood work revealed a creatinine of 8.5 mg/dL and blood urea nitrogen of 33 mg/dL. The possibility of kidney transplantation had been discussed with the patient, as it is likely her kidneys will not recover.

DISCUSSION

Although ethylene glycol in itself is a fairly nontoxic substance, it is metabolized to several toxic substances, including glycolic, glyoxylic, and oxalic acid by alcohol dehydrogenase.[1,2] These metabolites are responsible for producing the anion gap metabolic acidosis and CNS, cardiopulmonary, and renal sequelae typically associated with ingestion of ethylene glycol.[3,4]

The minimum lethal dose of ethylene glycol is estimated to be 100 mL for a 70 kg adult or 160 mg/kg body weight.[5] There is controversy related to the dose of ethylene glycol necessary to cause renal damage. However, there is some evidence suggesting that renal damage is related more to plasma glycolic acid levels than to plasma ethylene glycol concentrations.[5] In our patient, serum toxin screening was negative for ethylene glycol, suggesting that all the ethylene glycol ingested was broken-down into toxic metabolites. The chronic precipitation of calcium oxalate crystals in the renal parenchyma and tubules led to her renal failure.

This case illustrates an unusual presentation of ethylene glycol toxicity. In two similar cases of renal failure due to low-dose ethylene glycol ingestion in which ethylene glycol was not detected by drug screens, renal failure developed, and the unclear etiology of the renal failure prompted kidney biopsy have been reported previously.[6,7] Only after the biopsy results were obtained and revealed to the patients was the diagnosis established.

Our case differs from these cases in the time course between ingestion of ethylene glycol and presentation of renal failure and in the frequency of ethylene glycol ingestion. In the case reported by Nizze et al., the patient reported drinking rocket fuel, a substance known to contain ethylene glycol, three to four times, twelve years prior to the diagnostic work-up for renal failure.[6] While this case involves multiple ingestions of an ethylene glycol containing substance, the extended time course between consumption and presentation differs from our case. Additionally, rather than presenting with ARF, the patient was diagnosed with chronic renal failure of unknown origin which prompted the kidney biopsy. In the case reported by Sahoo, the patient, a 44-year-old man, presented with a three-day history of nausea, vomiting, and oliguria.[7] After receiving the biopsy results, the patient admitted to consuming 2–3 capsful of antifreeze prior to the development of his symptoms. Although this case describes a situation of low-dose ingestion of ethylene glycol, the patient did not display the long-term and frequent consumption pattern of our patient. The case report did not provide the patient's clinical outcome.

DECLARATION OF INTEREST

The authors of this manuscript do not have any conflict of interest. No funding was received.