Renal Grand Rounds – What Lurks in the Gap

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I recently presented the case of a
middle-aged man with a history of a remote Roux-en-Y gastric bypass, chronic
diarrhea, and colon cancer on chemotherapy who initially presented
with progressive fatigue and weakness in the setting of increased diarrhea.
Shortly after admission he developed agitation that progressed to
encephalopathy with dysarthria. His baseline labs from a month prior to
presentation were notable for a chronically low serum bicarbonate of 15-17 with
no anion gap. When he presented he was hypokalemic to 2.5 and his bicarbonate
had dropped to 11 with a new elevated anion gap of 25 and normal L-lactate.
Metabolic acidosis was confirmed on VBG. Interestingly, his urine electrolytes
demonstrated a positive urine anion gap of 26.

He was ultimately diagnosed with D-lactic
acidosis based on his clinical presentation which was confirmed with a serum
D-lactate of 6.28. For the week prior to admission, he had been drinking 1.5 L
of Gatorade (224 g of sugar!) daily to replace diarrhea losses.

This was a classic presentation of D-lactic
acidosis in which overgrowth of gram positive anaerobes in the setting of short
bowel syndrome is combined with a large carbohydrate load resulting in bacterial
fermentation and D-lactate production.  He even had the classic neurologic
findings!  His chronic non-gap acidosis likely represented chronic
diarrhea and D-lactate production, and his rising anion gap when he presented
was consistent with increased D-lactate production.

In D-lactic acidosis, the findings of hypokalemia
and a positive urine anion gap can provide a helpful clue. With elevated serum
D-lactate levels, the fractional excretion of D-lactate approaches 100%, i.e.
everything that’s filtered is excreted. This is because the stereospecificity
of the sodium-L-lactate cotransporter in the proximal tubule results in poor
reabsorption of D-lactate relative to L-lactate. The negatively charged
D-lactate essentially drags positively charged sodium and potassium into the
urine causing hypokalemia as well as a positive urine anion gap (Na + K – Cl)
due to the increased urine sodium and potassium.

This patient did well after his Gatorade was
cut off and he was treated with antibiotics to address gram positive anaerobic

Posted by Patrick Reeves

(Image taken from here – an educational blog for ED residents)


  1. We did not have a urinary osmolar gap. I do not have the numbers to hand but the urinary anion gap was strongly positive. Along with the low urine pH, this suggested the presence of an unmeasured anion in the urine. Agree that osmolar gap would add to this too as a confirmatory test but we felt it was not necessary given the low urine pH (which suggests that an RTA is not present).

  2. Interesting case. Can you please show us the urine electrolytes? Urine osmolar gap would be more helpful when you suspect high execration of negative anion in the urine.

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