What are the implications of elevated ammonia levels in urine?

From the Guidelines

Ammonia in urine is a waste product of protein metabolism, and elevated levels can occur with conditions like urinary tract infections (UTIs) or liver dysfunction, so it is essential to stay well-hydrated, treat underlying UTIs, and consider reducing protein intake if recommended by a healthcare provider. To manage ammonia in urine, the following steps can be taken:

• Stay well-hydrated by drinking 6-8 glasses of water daily to help dilute the urine and reduce the concentration of ammonia.
• Treat any underlying UTIs with appropriate antibiotics to prevent bacteria from converting urea back to ammonia.
• Maintain good hygiene to prevent UTIs.
• Consider reducing protein intake if recommended by a healthcare provider, as high protein intake can increase ammonia production. According to the study by 1, hyperammonaemia is defined as >100 µmol/l (170 µg/dl) in neonates or ≥50 µmol/l (85 µg/dl) in term infants, children, and adolescents, and can be managed with non-kidney replacement therapy (NKRT) and kidney replacement therapy (KRT). The study by 1 also provides guidelines for the management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy, including the use of ammonia-scavenging agents and dialysis. It is crucial to consult a healthcare provider if a persistent strong ammonia smell in urine is noticed, especially with other symptoms like pain during urination or fever, as it may indicate an infection or other medical condition requiring treatment. Some key points to consider:
• Normal urine contains small amounts of ammonia, typically 0.5-1.0 g/day.
• Elevated ammonia levels in urine can occur with certain conditions like UTIs or liver dysfunction.
• Dehydration concentrates urine components, including ammonia, intensifying its smell.
• The management of hyperammonaemia is challenging in pediatric populations given the non-specific clinical symptoms, the age-specific aetiologies, and the lack of consensus in the treatment plan.
• The study by 1 provides a PICO model table to illustrate the inclusion and exclusion criteria for the management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy. These actions are considered to be results of the following: Bacterial degradation of lactulose in the colon acidifies the colonic contents. This acidification of colonic contents results in the retention of ammonia in the colon as the ammonium ion Since the colonic contents are then more acid that the blood, ammonia can be expected to migrate from the blood into the colon to from the ammonium ion. The acid colonic contents converts NH3 to the ammonium ion (NH4)+,trapping it and preventing its absorption. The laxative action of the metabolites of lactulose then expels the trapped ammonium ion from the colon Experimental data indicate that lactulose is poorly absorbed. Lactulose given orally to man and experimental animals resulted in only small amounts reaching the blood. Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours The ammonia is trapped in the colon as the ammonium ion and then expelled, it is not expected to be found in high amounts in the urine. The urinary excretion of lactulose is 3% or less 2.

From the Research

Ammonia in Urine

• Ammonia in urine can be an indicator of various health issues, including urinary tract infections and kidney disease 3, 4.
• Hyperammonemia, a condition characterized by high levels of ammonia in the blood, can occur in patients with urinary tract infections, particularly those with urinary retention 3.
• The kidneys play a crucial role in regulating acid-base balance by excreting ammonia into the urine, and impaired kidney function can lead to acid retention and metabolic acidosis 4, 5.
• Elevated urinary ammonium has been associated with kidney stone disease, particularly struvite stones, and patients with elevated urinary ammonium tend to have higher rates of comorbid metabolic conditions, urinary tract infections, and bowel surgery 6.
• Urine osmolal gap (UOG) can be used to estimate urinary ammonium concentration, and a significant relationship has been found between UOG/2 and urinary ammonium in patients with chronic kidney disease 7.

Causes and Associations

• Urinary retention obstruction is a significant cause of hyperammonemia in urinary tract infections 3.
• Elevated urinary ammonium has been linked to acidosis, diarrhea, high protein diets, and pathogenic bacteria 6.
• Patients with chronic kidney disease may experience acid retention and metabolic acidosis due to impaired kidney function, and urinary ammonia levels can be used to gauge the renal response to acid loads 5.

Measurement and Estimation

• Direct measurement of urinary ammonia levels is the most accurate method of assessment, rather than indirect assessments 5.
• Urine osmolal gap (UOG) can be used to estimate urinary ammonium concentration, but the formula U-NH4+ = UOG/2 may overestimate the measured value 7.