Renally Generated Ammonia as a Cause of Hyperammonaemic Non-Hepatic Encephalopathy

Encephalopathy with high ammonia levels is most commonly associated with cirrhosis or urea cycle disorders, but it can also result from renal ammoniagenesis when renal excretion of ammonium is impaired. In the literature, this has been shown to occur in the presence of (1) urinary diversion to a segment of intestine; (2) urea-splitting microorganism overgrowth in the bladder or (3) renal tubular acidosis. However, hyperammonaemic encephalopathy can still occur without any of these overt factors. We present the case of a 76-year-old male who developed two episodes of hyperammonaemic encephalopathy in the setting of high output ileostomy. The first instance occurred with acute kidney injury (AKI) in the setting of post-operative sepsis, with vomiting causing hypokalaemia and metabolic alkalosis that subsequently evolved into normal anion gap metabolic acidosis (NAGMA). The patient recovered but presented months later with AKI, NAGMA and elevated ammonia. This resolved with fluids and bicarbonate replacement. Hypokalaemia, acidosis, corticosteroids and aldosterone stimulate renal ammoniagenesis. In some patients, renal ammonium excretion is sufficient under baseline conditions but not with decreased renal perfusion and increased ammoniagenesis. In such situations, impaired excretion of renally generated ammonium is suggested by elevated serum ammonia level accompanied by more-positive-than-expected urine anion gap in the setting of hypokalaemia or acidosis. Identifying patients who might benefit from immediate correction of these factors is important to permit attempts to suppress renal ammoniagenesis.