Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis.

OBJECTIVE: To correlate serum glycolic acid levels with clinical severity and outcome in ethylene glycol poisoning and to determine if glycolic acid levels are predictive of renal failure and the need for hemodialysis. METHODS: We measured serum ethylene glycol and glycolic acid levels by gas chromatography/mass spectrometry for 41 admissions (39 patients) for ethylene glycol ingestion and performed retrospective chart reviews. RESULTS: Eight patients died, all of whom developed acute renal failure. Of the survivors, 15 also developed acute renal failure, whereas 18 did not. Of those with normal renal function, 8 had glycolic acid levels below detection limits (< 0.13 mmol/L) despite ethylene glycol levels as high as 710 mg/dL; 7 of these patients coingested ethanol. Pertinent initial laboratory data for each group are as follows (mean; range): Deceased: pH 6.99 (6.82-7.22); bicarbonate, 4.8 mmol/L (2-9); anion gap, 28.6 mmol/L (24-40); glycolic acid, 23.5 mmol/L (13.8-38.0); ethylene glycol, 136.5 mg/dL (6-272). Survived/acute renal failure: pH 7.07 (6.75-7.32); bicarbonate, 5.6 mmol/L (1-12); anion gap, 28.7 mmol/L (18-41); glycolic acid, 20.2 mmol/L (10.0-30.0); ethylene glycol, 238.8 mg/dL (12-810). No acute renal failure with glycolic acid > 1.0 mmol/L: pH 7.29 (7.12-7.46); bicarbonate, 14.7 mmol/L (4-23); anion gap, 16.5 mmol/L (10-26); glycolic acid, 6.8 mmol/L (2.6-17.0); ethylene glycol, 269.1 mg/dL (6-675). No acute renal failure with glycolic acid < 1.0 mmol/L: pH 7.41 (7.38-7.47); bicarbonate, 23.4 mmol/L (17-25); anion gap, 11.8 mmol/L (8-18); glycolic acid, 0.1 mmol/L (0-0.66); ethylene glycol, 211 mg/dL (8-710). The mean time postingestion to admission generally correlated with severity as follows: deceased, > or = 10.4 h; survived/acute renal failure, > or = 9.9 h; no acute renal failure with glycolic acid > 1.0 mmol/L, > or = 6.2 h; no acute renal failure with glycolic acid < 1.0 mmol/L, > or = 3.7 h. Hematuria was more prevalent than oxaluria (86% and 41%, respectively), but neither was individually predictive of acute renal failure. Good correlations were found between glycolic acid levels and anion gap (r2 = 0.7724), pH (r2 = 0.7921), and bicarbonate (r2 = 0.6579); poor correlations (r2 < 0.0023) occurred between ethylene glycol levels and glycolic acid, pH, anion gap, and bicarbonate. Measured ethylene glycol values were highly correlated with ethylene glycol values calculated from the osmolal gap (r2 = 0.9339), but the latter overestimates the true value by about 7%, on average. An initial glycolic acid level > or = 10 mmol/L predicts acute renal failure with a sensitivity of 100%, a specificity of 94.4%, and an efficiency of 97.6%. Ethylene glycol levels are not predictive of acute renal failure or central nervous system manifestations of toxicity. If only ethylene glycol values are available (measured or calculated), an initial anion gap > 20 mmol/L is 95.6% sensitive and 94.4% specific for acute renal failure when ethylene glycol is present. Likewise, initial pH < 7.30 is 100% sensitive and 88.5% specific for acute renal failure. CONCLUSION: We propose glycolic acid > 8 mmol/L as a criterion for the initiation of hemodialysis in ethylene glycol ingestion. Patients with glycolic acid < 8 mmol/L probably do not need dialysis, regardless of the ethylene glycol concentration, when metabolism of ethylene glycol is therapeutically inhibited. In the absence of glycolic acid values, an anion gap > 20 mmol/L or pH < 7.30 predicts acute renal failure.

Simultaneous determination of ethylene glycol and glycolic acid in serum by gas chromatography-mass spectrometry.

We describe a gas chromatographic-mass spectrometric (GC-MS) procedure for the simultaneous determination of ethylene glycol (EG) and its major toxic metabolite, glycolic acid (GA), in serum. In this method, serum (50 microL) is treated with 150 microL of glacial acetic acid/acetonitrile (1:10, v/v; contains internal standard, 1,3-propanediol, 15 mg/dL) to precipitate protein. After centrifugation, 10 microL of supernate is treated with 500 microL of 2,2-dimethoxypropane/dimethylformamide (80:20, v/v) to convert water to methanol, and the volume is then reduced to < 100 microL of dimethylformamide (but not to dryness). After formation of tertbutyldimethylsilyl derivatives, analysis is performed by capillary column GC-MS in selected ion mode. The method gives a linear response to 1000 mg/L each EG and GA (16.1 mmol/L and 13.2 mmol/L, respectively) and has a lower limit of detection and a lower limit of quantitation of 10 mg/L each EG and GA (0.16 mmol/L and 0.13 mmol/L, respectively). Total assay imprecision is CV < or = 6.4% (200 and 800 mg/L EG and GA [3.2 and 12.9 mmol/L EG; 2.6 and 10.5 mmol/L GA, respectively]). Absolute recovery from human serum was 91.1% for EG and 77.6% for GA. The procedure is free from any known interference. A complete analysis set (three calibrators, patient serum neat, patient serum diluted 1:5 (v/v), and two controls) may be completed in about 2 h. A preliminary result, based on a single calibrator and patient serum diluted 1:5 (v/v), is complete in about 1 h. The method has been used to aid the diagnosis and management in 34 cases of EG intoxication. Selected cases are briefly reviewed.

Urolithiasis associated with the protease inhibitor indinavir.

OBJECTIVES: To report the association between the protease inhibitor indinavir and the development of urolithiasis. METHODS: Case reports of three adult patients infected with the human immunodeficiency virus who developed surgical renal stones while being treated with indinavir are presented. RESULTS: Of the 3 patients requiring surgical intervention, stone analyses were available in 2. One stone revealed an inner core of an unidentifiable crystal surrounded by calcium oxalate, and another was found to have indinavir components as determined by thin-layer chromatography and gas chromatography-mass spectrometry. Metabolic evaluation of all 3 patients identified significant hypocitraturia as an isolated finding. CONCLUSIONS: The widely used protease inhibitor indinavir is associated with the development of urolithiasis and may act as a nidus for heterogeneous nucleation leading to the development of mixed urinary stones. Surgical intervention may be necessary in some cases. Underlying metabolic abnormalities may contribute to the increased incidence of stone formation. Urologists and other health care providers should be aware of this association, as combined medical and surgical intervention may be necessary.