To Eat or Not to Eat

Parents of children with Nephrogenic Diabetes Insipidus (NDI) often complain that their kids would rather drink water than eat.

"Our son's nutritionists, pediatricians and nephrologists can't seem to have any answers to explain why he is not eating, say one worried couple. "We don't know why these children don't have an appetite," says a clinical nutritionist at the Children's Hospital of Philadelphia. "But we've seen that a large majority of these patients don't eat well." Dr. Darla Everly and Dr. Kevin Meyers at the Children's Hospital of Philadelphia have extensive experience with young children who have NDI. "Most children with NDI exhibit a lack of appetite in the first few years of their lives," says Meyers. Dr. Daniel Bichet, a member of DiF's Scientific Advisory Committee and leading expert in NDI, concurs. "Young boys with NDI usually have feeding problems early on," he says. "More so when they've suffered dehydration episodes." The good news is that most children improve with age, according to Dr. Nine M. Knoers, who has 15 years of experience working with people with NDI. "Many older children eat well and do have some appetite, and their does weight normalize," she says.

There are a number of theories about why young children with NDI tend not to eat well. "It is not clear why some children with NDI grow more slowly and seem to eat less than other children. Their appetites could be poor because their stomachs are so often filled with water," says Dr. Gary Robertson, the chair of DiF's Scientific Advisory Committee, and professor of medicine at Northwestern University. It's consistent with the fact that they usually start to eat and grow better when they are started on treatment that reduces their urine output and fluid intake. But it is inconsistent with the fact that children with untreated pituitary [neurogenic] DI often drink nearly as much water but seem to eat and grow more normally.

Yet another possibility is that "the genetic mutation that causes NDI also interferes with taste or appetite," says Robertson. "That too seems rather unlikely, since reducing urine output seems to improve eating and growth even though it doesn't correct the receptor defect caused by the mutation."

Gastroesophageal reflux, fairly common in children with NDI, might have something to do with it, in that these children learn as infants that some oral sensations are unpleasant, or even hurtful. But Meyers points out "not all children with NDI have reflux."

And it seems equally unlikely that the bland diet NDI children are often put on discourages their eating. "Many children with NDI start to eat and grow more normally when they are started on effective treatment, which includes a low-salt diet," says Robertson. As Everly notes, "We are not born with a salt craving, it's a learned taste."

Dr. Heinz Valtin, founding vice president of DiF and an emeritus professor at Dartmouth Medical School, notes that appetite or satiety receptors are located in the hypothalamus, as are, of course, the cells that produce the antidiuretic hormone (ADH, or vasopressin). "In NDI, these cells are hyperstimulated and vasopressin is overproduced," Valtin says. He wonders about possible spillover of nervous impulses within the hypothalamus or some feedback mechanism that would inhibit appetite. "Currently, much attention is focused on a protein called leptin, which seems to regulate eating behavior, possibly by combining with satiety receptors in the hypothalamus," states Valtin.

Robertson concludes, "not one of the existing theories adequately explains the fact that these children have poor appetite and growth." The bottom line is that this is worth studying, according to Everly. "Obviously their eating affects their growth and development," she says. "But we just don't know if there's any physical reason for it. And until we do, we can't really be sure what approach to take to the problem."