The Case | A woman with severe metabolic acidosis

make your diagnosis

http://www.kidney-international.org & 2010 International Society of Nephrology Kidney International (2010) 77, 261–262; doi:10.1038/ki.2009.437

The Case | A woman with severe metabolic acidosis Yu-Ming Chang1, Yeong-Woei Chiew1 and Chwei-Shiun Yang1 1

Division of Nephrology, Department of Medicine, Cathay General Hospital, Taipei Medical University, Taipei, Taiwan, ROC

Correspondence: Chwei-Shiun Yang, Division of Nephrology, Department of Medicine, Cathay General Hospital, No. 280, Section 4, Ren-Ai Road, Taipei Da An 106, Taiwan, ROC. E-mail: [email protected]

Table 1 | Laboratory findings on arrival Our case Blood urea nitrogen (mg/dl) Creatinine (mg/dl) Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) Serum glucose (mg/dl) Serum osmolality (mmol/kg) Serum osmolar gap (mmol/l) pH PaO2 (mm Hg) PaCO2 (mm Hg) Bicarbonate (mmol/l) Base excess (mmol/l) SaO2 (%) Serum anion gap (mmol/l) Lactate (mmol/l) Ketone body

A 86-year-old woman was brought to the emergency room with tachypnea, mental confusion, and cerebral ataxia. She had history of chronic renal failure and perforated peptic ulcer, and had undergone oversew perforation, and gastrojejunostomy for subsequent intestinal obstruction 1 year ago. She had regularly taken Biofermin supplements (containing Lactobacillus acidophilus) and mulberry juice mixed with sugar and honey during the previous 3 days. She denied taking any toxins. On examination she was malnourished.

103 3.4 143 4.4 118 137 339 8.6 7.22 188.6 9.6 3.9 23.7 99.1 21.1 2.6 Negative

Reference value 6–20 0.5–1.5 135–145 3.5–5.0 98–110 70–110 275–295 0–15 7.35–7.45 80–105 35–45 22–26 3.3 to 2.3 95–100 10–12 0.7–2.1 Negative

Her blood pressure was 180/96 mm Hg, respiratory rate 42/min, and body temperature 36.8 1C. An abdominal X-ray showed distended intestinal loops. A computed tomography scan of the brain was normal. The pertinent laboratory findings on arrival are shown in Table 1. Emergent hemodialysis was performed due to severe metabolic acidosis refractory to intravenous sodium bicarbonate. Her tachypnea and neurological symptoms dramatically improved after hemodialysis.

What is the cause of her acidosis?

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Y-M Chang et al.: D-lactic acidosis

The Diagnosis | High anion gap metabolic acidosis from D-lactic acid Glucose

Pyruvate

ADP

Pyruvate dehydrogenase

ATP

Acetyl-CoA O2

CO2+H2O

D-2-hydroxy

acid dehydrogenase

D-Lactate

Overgrowth of acid resistant Gram-positive anerobes (such as Lactobacillus, the major D-lactate producer)

Organic acids production

High carbohydrate loading

Glucose fermentation in the colon

Short or bypass small intestine

Figure 1 | The pathogenesis of D-lactic acidosis.

This patient had high anion gap metabolic acidosis. Ketoacidosis and lactic acidosis were excluded by negative blood ketones and normal L-lactate levels. Intoxication (such as that from methanol, ethylene glycol, or salicylate ingestion) was unlikely due to lack of history and normal serum osmolar gap. Severe metabolic acidosis was out of proportion to the degree of renal failure. Therefore, the blood was screened for other possible acids. D-Lactate is normally undetectable, and in this patient the measured concentration was elevated at 6.8 mmol/l (o0.1 mmol/l in normal individual). D-Lactic acidosis was first reported in a male with short bowel syndrome in 1979.1 Since then this entity has been reported in patients with jejunoileal bypass, small bowel resection, and other causes of short bowel syndrome or malabsorption syndrome. The clinical manifestation is characterized by episodes of encephalopathy and metabolic acidosis. The encephalopathy was thought to be due to not only D-lactate but also other unidentified co-products by colon flora.2 The development of D-lactic acidosis was shown as Figure 1. In this case, a large amount of carbohydrate intake, combined with gastrojejunal bypass, diminished colonic motility, and an additional diet supplement containing lactobacilli enhanced the production of D-lactic acid.3 Impaired renal function further reduced its excretion. 262

Humans have a capacity to metabolize D-lactate to pyruvate by the enzyme D-2-hydroxy acid dehydrogenase. D-Lactic acidosis should be strongly considered in the patient with short bowel or other malabsorption syndrome, high anion gap metabolic acidosis, negative ketones, and normal serum concentration of L-lactate. Neurologic symptoms and signs are also clues. Definite diagnosis required direct measurement of D-lactic acid. The standard assay for lactate uses L-lactate dehydrogenase, which will not detect D-lactate. Treatment includes withholding enteral carbohydrate, intravenous bicarbonate solution, and rehydration. Oral antimicrobial agents against acid-resistant lactobacilli, such as metronidazole, neomycin, or vancomycin, may be useful. Hemodialysis could be an effective treatment for severe D-lactic acidosis. ACKNOWLEDGMENTS

We thank Professor Shih-Hua Lin, Division of Nephrology, Tri-Service General Hospital Taipei, Taiwan, for measuring the D-lactate concentration. REFERENCES 1. 2. 3.

Oh MS, Phelps KR, Traube M et al. Dh-Lactic acidosis in a man with the short bowel syndrome. N Engl J Med 1979; 301: 249–252. Halperin MI, Kamel KS. D-lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int 1996; 49: 1–8. Ku WH, Lau DCY, Huen KF. Probiotics provoked D-lactic acidosis in short bowel syndrome: case report and literature review. HK J Paediatr 2006; 11: 246–254. Kidney International (2010) 77, 261–262