Polyethylene Glycol 3350 Crystal Nephropathy in Association With Glomerular Mesangial Immunoglobin A Deposition

Abstract

Polyethylene glycol (PEG) 3350, an active ingredient of over-thecounter MiraLAX, is a commonly used laxative in children and is produced by polymerization of ethylene glycol (EG). Masked EG toxicity secondary to contamination of PEG 3350 could occur. We present a 7-year-old child with developmental delay who presented with altered mental status and acute kidney injury (AKI) following intake of generic PEG 3350 for few days prior to presentation. There was high anion gap metabolic acidosis, hypernatremia, elevated osmolar gap, lactic acidosis, and AKI. Urinalysis showed tubular proteinuria, microscopic hematuria, and calcium oxalate crystals. Prior urinalyses were normal without hematuria or proteinuria. Renal biopsy revealed evidence of mesangial dominant immunoglobulin A (IgA) and complement 3 (C3) deposits along with dense tubular deposition of calcium oxalate crystals. He subsequently developed worsening oliguric AKI and required hemodialysis (HD) for several sessions. The AKI resolved within 2 weeks and further HD was not required. Mental status improved in few days. Follow-up urinalyses showed resolution of microscopic hematuria and crystalluria. We hypothesized that the generic PEG 3350 most likely was contaminated with EG leading to the presentation. A high index of suspicion of contamination of PEG 3350 with EG is required in patients presenting with unexplained high anion gap metabolic acidosis, elevated osmolar gap, lactic acidosis, AKI, calcium oxalate crystalluria, and oxalate crystals on renal biopsy. Further studies are needed to determine whether there is an association between transient glomerular mesangial IgA deposition and crystal nephropathy.

Effects of diethylene glycol contamination of pharmaceutical products on unexplained acute kidney injury in children: a systematic review

“…22) Ergocalciferol contains 103.6 g/100 mL of PG, and 600,000 IU is equivalent to 75 mL of the solution or 77.7 g of PG. Another study by Aly et al 20) revealed that an EG-contaminated laxative was the primary cause of AKI in a boy with a complicated congenital disease. Based on the renal biopsy evaluation, the drugs were suspected to be contaminated with EG.…”

“…13) Most studies have been case reports of a single patient with DEG-induced unexplained AKI. 7,[20][21][22][23][24][25][26][27][28][29] Some case reports described unintentional EG contamination or DEG-induced oliguria or anuria 21,24,27,29) after the consumption of a DEG-contaminated acetaminophen elixir, 26) PG-containing intravenous phenobarbital and pentobarbital for uncontrolled seizures, 28) DEG ingestion suicide attempts, 7) ergocalciferol-containing high-dose vitamin D dissolved in PG for diagnosing nutritional rickets, 22) intentional EG poisoning in baby formula, 25) DEG-contaminated fever and cough medication, 23) and EG contamination of laxatives. 20) High-quality studies of AKI induced by DEG and other glycol-induced AKI are limited.…”

“…7,[20][21][22][23][24][25][26][27][28][29] Some case reports described unintentional EG contamination or DEG-induced oliguria or anuria 21,24,27,29) after the consumption of a DEG-contaminated acetaminophen elixir, 26) PG-containing intravenous phenobarbital and pentobarbital for uncontrolled seizures, 28) DEG ingestion suicide attempts, 7) ergocalciferol-containing high-dose vitamin D dissolved in PG for diagnosing nutritional rickets, 22) intentional EG poisoning in baby formula, 25) DEG-contaminated fever and cough medication, 23) and EG contamination of laxatives. 20) High-quality studies of AKI induced by DEG and other glycol-induced AKI are limited. Our study summarized that most studies revealed that the outbreak of unexplained AKI originated from DEGcontaminated pharmaceuticals, including paracetamol, a mixture of paracetamol and diphenhydramine hydrochloride, a mixture of bromhexine HCL and pseudoephedrine HCL, a sedative mixture, adverse drug reactions from the teething tincture, unspecific cough syrups, and unintentional poisoning.…”

“…PG overconcentration and EG contamination are common medications, such as antiseizure agents, 28) vitamin D treatments, 22) and laxative agents. 20) One study reported the adverse drug effects of high-dose intravenous phenobarbital and pentobarbital for uncontrolled seizures after the failure to prescribe standard medicine for seizures. During the 8-day treatment, 6.53 g/day of pentobarbital and 6.70 g/day of phenobarbital were infused, comparable to the ingestion of 90.3 g/day of PG.…”