Treating NDI: Emphasizing the First Year of Life
by Darla Everly, CNSD; Bernard S. Kaplan, M.D.; and Kevin Meyers, M.B., B.Ch., Children's Hospital of Philadelphia

Children with nephrogenic diabetes insipidus (NDI) are unable to concentrate their urine, requiring them to drink large volumes of water. This impacts them the most during the first few years of life, when nutrition may take a backseat to preferential drinking. The fluid requirements in these children can be decreased in a number of ways, which may increase their caloric intake and improve their growth.

Growth and Development in Children with NDI in the First Year of Life

We looked at growth in the first year of life in our patients with NDI because we noticed that the greatest degree of growth failure seemed to occur in this age-group. The patients’ birth weights and heights were at or above the 50^th percentile on the National Collaborative Health Study growth charts. However, growth throughout the first year showed a decline in velocity and many of the patients fell below the 5^th percentile for weight and height. The height velocity was less than 80% in three of the four children (50%, 76%, 77%) and 100% in one child studied during the first year of life. Close attention to calorie intake improved weight and height gain in three of the four children, and height gain improved in the other child.

The causes of this growth failure have not been systematically studied. It may be due in part to inadequate calorie intake, as these children prefer water to food, milk, or formula. However, additional contributing factors may include bouts of dehydration or the presence of gastrointestinal (GI) symptoms such as disturbances in GI motility, reflux, or early satiety.

Water

Water must be available at all times, in all places, and for every occasion. (The bathroom must also be.) Urine volumes off therapy and without attention to salt intake vary from 3 to 10 gallons (12 to 50 liters) per day. Even in the face of dehydration, urine osmolality is always maximally dilute, that is 50-100 mOsm/l. Hence the name insipidus as the child’s urine typically looks like water and has no taste (insipid means bland, tasteless, dull, unexciting). Children with NDI typically prefer ice-cold water, which seems to quench their thirst more quickly than warm water. The reason for this is not known. Children with NDI will drink in preference to eating. These large volumes of fluid taken by small children leads to a feeling of fullness and they have both decreased will and time to eat. Additional factors that may influence food ingestion include alterations in upper gastrointestinal tract motility, alterations in the set point of the satiety center, and in taste.

Strategies to Reduce Water Intake

Medications: Therapy may include a combination of one of three medications including Indomethacin (Indocin), Amiloride (Midamor), and Hydrochlorothiazide (Hydrodiuril) or Chlorothiazide (Diuril). Urine volumes will decrease to 1 to 3 gallons (4 to 12 liters) per day with appropriate therapy (please refer to page 10). This is a more manageable, although still large, volume of urine. Parents and treating physicians need to be aware that medication-related side effects are a further factor, which may influence food ingestion. Continued next page

To excrete large amounts of waste (protein, electrolytes) either the urine must be concentrated or the waste must be excreted in large volumes of dilute urine. In practical terms this translates into a requirement for different volumes of urine to remove a solute load. In children with NDI, who have defective urinary concentrating ability, excessive intake of salt will increase urine volumes. If the urine concentration is set at 200 mOsm/l then to excrete:

1 g NaCl = 77 mEq/l needs 77/200 x 1 liter = 385 mls

10g NaCl = 770 mEq/l needs 770/200 x 1 liter = 3850 mls

If the urine concentration is set at 50 mOsm/l then to excrete:

1 g NaCl = 77 mEq/l needs 77/50 x 1 liter = 1540 mls

10g NaCl = 770 mEq/l needs 770/200 x 1 liter = 15400 mls

This is why salt reduction is a major focus of nutritional therapy of NDI. The recommended amount of sodium is less than 2 g/day. Sodium restriction is not the sole treatment of NDI but should be used as an adjunct to medications. We are not born with a salt craving, this is a learned taste. Excessive salt and sodium intake will also result in the stimulation of thirst, which contributes to increased water intake.

Salt versus sodium

Salt and sodium are not the same. Sodium (Na) is a mineral that is found in most substances including water. Salt refers to the combination of sodium and chloride (NaCl), which is found naturally in foods such as milk. The majority of the sodium we eat is in the form of salt.

The first step to reduce dietary salt is to identify the high-salt sources routinely consumed. Some of these include table salt, seasoning that contains salt, processed foods, and foods that have naturally occurring sodium. Once identified, it is time to start making substitutions in the current diet to achieve a lower salt intake. Here are some suggestions on how to achieve this goal [please refer to DiF’s Web site or to the Spring 1999 issue of Endless Water for more information about low-sodium cooking strategies]:

1. Eliminate table salt used in cooking or seasoning. This doesn’t mean food has to be bland. Replace table salt with herbs, salt-free spices, and salt substitutes. For example, choose garlic powder over garlic salt.
2. Avoid processed foods such as luncheon meats, bacon, ham, sausage, frozen dinners, and canned foods. Salt is added as a preservative in these foods. Replace these foods with fresh meats (i.e., chicken, turkey, ground beef) and fresh or frozen vegetables.
3. Replace high-salt snacks with salt-free potato chips and salt-free pretzels.

Hidden salt: Sodium is present in ALL foods, so it is important to beware of "hidden salt." The best way to identify high salt foods is to accurately evaluate the nutrition label, which can be found on every food product. Sodium content is expressed in milligrams on the label. Be aware that the sodium content reflects per serving so be sure to look at the serving size listed. Use a guideline of 150 mg or less per serving to determine if the product is appropriate.

Nutrition Goals and Therapy

Because Failure to Thrive (FTT) is often associated with NDI, nutritional therapy is crucial to help correct and/or prevent growth failure. The goal of nutrition is to maximize calorie intake to promote adequate growth or even "catch-up" growth. The first step is to determine appropriate daily calorie goals. This can be achieved by using the Recommended Daily Allowance (RDA) for age. Because the RDAs were developed to meet the nutrient needs of "healthy" children, it is necessary for additional calories to be added to account for any differences in energy needs or metabolism due to NDI. The energy requirements are individualized based on how much "catch up" is desired. For example, typical energy requirements for a FTT patient with NDI may be 120% to 140% of the RDA. Patients are evaluated on a monthly basis so that weight and height velocity can be followed closely. Changes in estimated calorie needs are adjusted based on adequacy of growth and weight gain.

Maximizing Nutrient Intake

To promote adequate growth and meet estimated calorie goals, it is often necessary to maximize the nutrient density of fluids and solids because of the overwhelming desire for water.

For infants, concentrating infant formula is a popular method to increase caloric density. There are several strategies to concentrate formula:

1. Do not add less water: This method causes increased formula osmolality and sodium content. Do not add less water: This method causes increased formula osmolality and sodium content.
2. Add modulars: Add modulars: They can be added to formula to increase calories. There are three types used for increasing calories:

The safest way to concentrate formula for NDI patients is to use one of these modular components. They increase the calorie content without affecting the water or sodium content. For children more than one year old, there are several methods to maximize caloric intake. We initially try to encourage oral intake, but enteral nutrition (tube feedings) is certainly indicated if a child is not able to consume adequate calories as determined by the medical team. Some suggestions to maximize oral intake are:

Conclusions

Young children with NDI have many challenging nutritional needs. From strict sodium restriction to maximizing nutrient intake, the overall goal is to consume adequate calories to achieve growth and to correct or prevent failure to thrive. Nutritional assessment and intervention in NDI needs to be an ongoing process that starts early in the first year of life with special attention paid to the fact that every child has unique nutritional habits and needs.

Darla Everly is a clinical nutritionist at the Department of Nutrition, and Drs. Meyer and Kaplan are attending and chief attending nephrologist, Department of Pediatrics, at the Children’s Hospital of Philadelphia, Philadelphia, PA.