Bedwetting Chemistry

A higher concentration of sodium and urea in urine could underlie a type of bedwetting in children that does not respond to the common medication, desmopressin. The levels of these natural substances could indicate an imbalance of the hormone-like compound prostaglandin, and suggests a new approach to treating this common problem.

Out of every ten children who frequently wet the bed, about three do not respond to treatment with the drug desmopressin, which works for the others. Now, Danish medical researchers think they know why, and it’s down to chemistry.

Urine output is controlled, in part, by our own internal daily clocks, or circadian rhythm. With the transition from day to night, our bodies reduce the amount of excreted water, electrolytes, and other metabolic end products in preparation for hours of sleep. We are not born with this circadian rhythm, but it usually develops in early childhood. Some children take longer to develop this rhythm and bedwetting spontaneously ceases. But for some the condition can last into young adulthood.

In 1989, Soren Rittig of the Aarhus University Hospital and colleagues discovered that the hormone vasopressin plays a role in urination. This finding led to the development of desmopressin, a synthetic analog of the related pituitary hormone, argipressin. The drug’s action is mediated by the receptor for vasopressin. However, Rittig and others were perplexed by the failure of desmopressin in 30% of bedwetters.

Now, Soren Rittig and colleague Jens Christian Djurhuus, in collaboration with Kaj Anker Jorgensen and Konstantinos Kamperis of the University of Aarhus, Denmark, have examined 46 children, aged 7–14 who failed to respond to desmopressin. The team collected blood and urine from the children during a second night in their care without waking them. This would give the researchers a more complete picture of physiological changes that occur through the course of the night.

Circadian variations in urine output were evident for all groups. However, children classed as polyuric—producing more than 130% of bladder capacity on a bed-wetting night—excreted twice as much urine during the night, compared to the non-polyuric children and the non-bedwetters in a control group. The researchers found that the urine of the polyuric children who wet their beds during the experiment contained more sodium, urea, and prostaglandin.

The researchers also measured other factors, such as blood pressure, heart rate, and levels of various hormones. These did not vary significantly, say the researchers. Moreover, vasopressin levels among bedwetters, whether the 130% plus group or not, did not vary.

“We found enuresis-related polyuria to be largely due to an abnormal nocturnal renal handling of solutes and, in particular, sodium,” Rittig explains. “While the study suggests that sodium is the main culprit among this subpopulation of enuretic children, there is much still to be done to understand how the process works.”

The team is now testing an alternative treatment, indomethacin, a drug that inhibits prostaglandin. Results for those trials will be complete by the end of 2007, Rittig says.

Research Blogging IconKamperis, K., Rittig, S., Jorgensen, K., & Djurhuus, J. (2006). Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to desmopressin treatment AJP: Renal Physiology, 291 (6) DOI: 10.1152/ajprenal.00134.2006