Hypocitraturia in common bottlenose dolphins (Tursiops truncatus): assessing a potential risk factor for urate nephrolithiasis.

Urate nephrolithiasis has been reported in marine mammals, including 14 common bottlenose dolphins (Tursiops truncatus) in a single population.10,36,39,40 Ammonium acid urate nephrolithiasis, in particular, has been associated with anemia, high serum creatinine, high BUN, low glomerular filtration rate, dilated collecting ducts, and hydronephrosis in dolphins.40 According to hundreds of necropsies conducted on wild dolphins over the past 20 y, nephrolithiasis appears to be primarily associated with managed collections and is not believed to be a significant disease in wild populations.8 To date, the cause of urate nephrolithiasis in dolphins remains unknown. Urate nephrolithiasis can be caused by uric acid, sodium acid urate, or ammonium acid urate calculi. Both uric acid and ammonium acid urate calculi have been reported in dolphins. However, archived dolphin calculi initially characterized as uric acid in the 1990s were retested by using polarizing light microscopy and recharacterized as pure ammonium acid urate.40 Therefore, the number of dolphin ammonium acid nephroliths incorrectly characterized as uric acid is unknown. In humans, urate nephrolithiasis, specifically uric acid nephrolithiasis, typically has been associated with high levels of uric acid in serum and urine and low urinary pH.5,23 However, people with type 2 diabetes mellitus can have pure uric acid nephrolithiasis in the face of low serum and normal urinary uric acid levels. Urate nephroliths may develop in people with type 2 diabetes due to the presence of low urinary pH, decreased ammonium excretion, a compensatory response of hypocitraturia, and further acidification of urine due to an impaired ammonia excretory response. This mechanism presumably is driven by insulin resistance.32 Humans with recurrent uric acid calculi can be at risk of developing ammonium acid urate calculi.35Ammonium acid urate calculi can result due to uric-acid- and ammonium-enriched urine and hypocitraturia.15,35 These calculi are endemic in Asian countries, and pure ammonium acid urate calculi are rare in industrialized countries.28 Other risk factors for ammonium acid urate calculi include inflammatory bowel disease and morbid obesity.35 In addition, urine-rich animal protein diets in humans have been associated with urate nephrolithiasis, including uric acid and ammonium acid urate calculi.13 Other animals susceptible to ammonium urate calculi include dogs, cats, and reptiles.7,14,20 Dalmatians are particularly susceptible to uric and ammonium urate calculi formation due to a recessive gene that results in defective urate metabolism. In cats and non-Dalmatian dogs, the pathogenesis of this disease is not well known. Changes in protein metabolism due to altered protein intake are hypothesized as risk factors for urate calculi formation in these animals.7,14 To determine whether managed collections of dolphins have risk factors for urate nephrolithiasis similar to those found in other animals, especially humans, urine samples from 94 animals were collected during April 2006 through June 2009 from 4 wild populations living off the coasts of Florida, Georgia, Mississippi, and North Carolina and from 4 managed collections, including a predominance of animals from the Navy Marine Mammal Program (MMP). In addition, urine uric acid and pH were tested in a subset of animals. Our null hypothesis was that there would be no significant differences in urinary creatinine, citrate concentration, uric acid concentration, and pH between wild and managed collection dolphins.