Author: Robertson, Gary
Apart from rare allergic reactions, the only recognized side effect of long term treatment with diuretics is potassium depletion (which can be prevented by increasing intake of potassium).
Author: Knoers, Nine
The drugs presently given to NDI patients help manage the symptoms of NDI, but do not cure the disorder. Since there is no known cure for inherited NDI, the person with this form of NDI will have it the rest of their life. However, with the proper type and combination of drugs an NDI patient can reduce the volume of water lost through urination and therefore the amount of water he or she needs to drink to replace the lost water. The danger with stopping the drug regime is that the NDI patient will have to greatly increase his intake of water to compensate for the water lost through urination. This could place great strain on the urinary system, leading to bladder extension and, though rarely, kidney failure. This is especially true for children. The best course of action is to stick with the drug regime given by your doctor and keep in contact with her if any adjustments in the regime are called for.
Author: Bichet, Daniel G.
Hydrochlorothiazide and amiloride are both diuretics. That is, they both normally act as agents that promote the excretion of urine. It seems somewhat paradoxical then, that these two agents are used to reduce the urine flow of NDI patients. In fact, researchers are still unable to explain exactly how these diuretics act as antidiuretics in NDI patients.
A normally functioning kidney reabsorbs the majority of the body water passing through it. The kidney reabsorbs the water through the nephrons and the collecting ducts they flow into. The nephron is the main working unit of the kidney. It consists of a filter, called a glomerulus, and a tiny tube called a tubule. The part of the tubule closest to the glomerulus is called the proximal tubule. The part furthest from it is called the distal tubule. The reabsorption process involves a host of molecular structures working properly and the creation of the proper osmotic conditions between the nephrons and the kidney tissue (interstitium) that surround them. A majority of the body water is reabsorbed through the proximal tubule, but a significant amount is also reabsorbed through the distal tubule and the collecting ducts. People with NDI cannot reabsorb the water flowing through the distal tubule and the collecting ducts.
Some researchers think that thiazide diuretics may reduce the rate at which body fluid filters through the glomerulus. The idea is that if there is a reduced amount of fluid going through the glomerulus, there will be a reduced amount of fluid reaching the distal tubule and the kidney collecting duct. But several studies have shown that thiazides have an antidiuretic effect without reducing the glomerular filtration rate.
Other researchers think that the urine reduction takes place because the thiazides reduce distal tubular sodium reabsorption, increase urinary sodium excretion, and lower extracellular liquid volume. These effects combine to cause an increase of body water reabsorption in the proximal tubules, so there is less fluid reaching the distal tubules and collecting ducts. But one study – the first that directly tested whether thiazides do reduce the amount of fluid that reaches the collecting ducts and distal tubules – showed that the reduction of fluid delivered to the distal tubule was too small to account for the degree of urine reduction. Most recently, a series of experiments designed by Gronbeck, et al., in 1998 found no evidence to support this reduction in fluid to the distal tubule theory. Nonetheless, in combination with a reduction in salt intake, thiazides can reduce urine volume by 20% to 50%.
Whereas thiazides rob the body of potassium, amiloride does not. Thus, it is referred to as a potassium-sparing diuretic. It blocks the transport of sodium from the outer and middle sections of the collecting ducts to the surrounding kidneytissue. Amiloride is less effective in reducing urine output than thiazides. But when it is used with thiazides it helps reduce the urine output more than when thiazides are used alone. Perhaps this additive effect is due to the fact that both diuretics affect different parts of the collecting ducts and distal tubules.
Indomethacin inhibits prostaglandin synthesis in the kidney and also decreases the glomerular filtration rate. Prostaglandins inhibit the ability of AVP to induce water reabsorption in the collecting duct. By reducing the concentrationof prostaglandins in the collecting duct, thus blunting the AVP inhibiting action of prostaglandins in this area, indomethacin can enhance the ability of AVP to concentrate urine. Indomethacin is fast acting and useful in emergency situations, but it is not recommended for long-term use because of its side-effects.
Author: Bichet, Daniel G.
When hydrochlorothiazide is used in combination with either amiloride or indomethacin, it results in a greater reduction in urine output than achieved by hydrochlorothiazide alone. Though it is still unclear how hydrochlorothiazide actually works to reduce urine output, many researchers think that hydrochlorothiazide causes the person taking it to secrete more sodium in the urine, thus reducing the amount of sodium in the kidney extracellular environment along with reducing the amount of extracellular fluid volume in the kidney. Less sodium and less extracellular fluid creates the osmotic conditions in the kidney that result in more body water than usual being reabsorbed in the part of the kidney nephron called the proximal tubule. This means there is less body water arriving at the distal nephron and collecting duct. (In NDI there is an inability to reabsorb the water flowing through the distal tubules and collecting ducts. This unabsorbed water becomes the excessive urine that is voided by NDI patients).
Amiloride also causes the body to excrete more sodium in the urine. This also results in reduced extracellular sodiumand fluid volume. But amiloride has its effect at a different part of the kidney than hydrochlorothiazide. So when the two drugs are used together, they both, working at different locations, cause increased sodium excretion, which changes the osmotic conditions to allow increased absorption of body water at different places in the kidney than the NDI-impaired collecting duct.
Indomethacin, on the other hand, works to reduce urine output by inhibiting prostaglandin synthesis in the kidney. Prostaglandins inhibit the hydroosmotic effect of AVP in the collecting duct. By blocking the action of prostaglandin in the collecting duct, indomethacin enhances the ability of AVP to concentrate urine.
Since the combination of amiloride and hydrochlorothiazide is as effective as the combination of indomethacin and hydrochlorothiazide, and since amiloride has fewer and milder side-effects than indomethacin and hydrochlorothiazide, most clinicians prefer amiloride, reserving indomethacin for emergency uses since its action begins more quickly than the diuretics.
Author: Knoers, Nine
The child’s electrolytes will be checked as part of the initial diagnosis to determine if he has NDI. Usually, this will happen when the child is an infant. The optimum drug regime for the infant will be in part determined by his electrolyte count. To determine the effectiveness of the drug regime, and to make any necessary adjustments in it, the infant will probably have to have his electrolyte count checked every two weeks at first. The infant will then have his electrolytes checked once a month, then, slowly, the checks can be spaced to once every half year. Children who were diagnosed in infancy or when very young will only be required to have his electrolytes checked annually by the time they are six or seven. There may be, however, situations in which the electrolyte count must again be checked more frequently. For example, the child may develop an illness that dehydrates him and adversely affect his electrolyte count.
Author: Robertson, Gary
The severity of NDI differs in different patients for several reasons including diet, age and the nature and locaton of the genetic mutation responsible for the disease.
Author: Robertson, Gary
NDI does not always stop when the drug or other cause stops because the damage to the kidney may be permanent especially if the cause has been present for a long time.
Author: Robertson, Gary
The severity of nephrogenic diabetes insipidus can be reduced by decreasing the intake of salt and, if possible, protein. However, this will not completely correct the problem. Fluid restriction may reduce urine output in some patients but it should never be tried as treatment because it will also result in hypernatremic dehydration and marked increase in thirst. Patients with severe hypernatremic dehydration can suffer small strokes that permanently damage the brain.
Author: Robertson, Gary
Sudden discontinuation of the medications used to treat nephrogenic diabetes insipidus is not dangerous and will have no adverse effect other than
- an abrupt worsening of the diabetes insipidus and
- possible hyperkalemia (increase in serum potassium) if potassium supplements are not reduced to match the decrease on potassium loss.
Author: Robertson, Gary
It is not surprising that Maxide reduces your urine output and fluid intake because it is the trade name for a combination of drugs that contains hydrochlorothiazide. Hydrochlorothiazide is one of the drugs known to be effective in reducing urine output in nephrogenic diabetes insipidus. The primary mechanism of action is on the kidney to reduce urine output. This reduces dehydration which secondarily reduces thirst and fluid intake.
Author: Robertson, Gary
DDAVP is used to treat the pituitary type of DI. Hydrochlorothiazide and amiloride are used to treat the nephrogenic type of DI. If your doctor prescribed DDAVP and it is working, you must have the pituitary type of DI. It is sometimes caused by eosinophilic granuloma.
Author: Robertson, Gary
If the DDAVP controls your son’s bedwetting, he does not have NDI since DDAVP does not work in NDI. However, he should be evaluated for possible pituitary DI. If the DDAVP does not control his bedwetting, your son could have nephrogenic DI, although there are also causes of bedwetting that are refractory to DDAVP treatment.
Author: Knoers, Nine
That depends on the severity of their symptoms. As we know in the vast majority of cases of inherited NDI, it is the female who carries the disease and the male who is born with it. However, sometimes the carrier female also expresses the symptoms of NDI, to a lesser or greater extent. In some cases, the female carrier’s symptoms will be as severe as the male NDI patient, in which case she must be treated with the same drug regime as males. Other female carriers have very mild expressions of NDI and can get by quite comfortable by just drinking a little more water in general.
Author: Robertson, Gary
Abnormalities in serum sodium primarily affect the brain. These effects vary depending on the severity and rapidity of the abnormality and can range all the way from mild weakness, lethargy and confusion all the way to convulsions, coma and rarely, even death. Most of the effects are reversible when the abnormality in serum sodium is corrected but occasionally, especially in patients with severe hypernatremic dehydration, small strokes occur that permanently damage the brain.
Author: Knoers, Nine
The significant side-effects of indomethacin, especially with long-term use, are gastrointestinal bleeding and ulceration, kidney toxicity, hyperkalemia (excessive potassium in the plasma), hyponatremia (abnormally low plasma levels of sodium).Indomethacin may cause fluid retention, peripheral edema and liver toxicity. The central nervous system can also be negatively effected.
The significant side-effects of hydrochlorothiazide, especially with doses greater than 50mg/day, can be hypokalemia(abnormally low plasma levels of potassium), hyperuricemia (excessive uric acid or urates in the blood), decreased glucose tolerance, and an increase in serum TRG and cholesterol. These side-effects also can occur with chlorothiazide. Since both these thiazide diuretics rob the body of potassium, there is also a possible risk of cardiac arrhythmia. Clinicians must often administer potassium salts along with these diuretics, and this may cause severe gastrointestinalcomplications.
There seems to be only one significant side-effect of amiloride use, and this would be to induce hyperkalemia. This is more likely to occur if the person taking amiloride already has compromised kidney function. Several studies have indicated that prolonged use of amiloride in combination with hydrochlorothiazide is usually well-tolerated.
Author: Knoers, Nine
For adults and older children, the normal range is 137 to 145 millimoles per liter. For infants, the normal range is somewhat lower, up to one or two millimoles per liter from the adult range. As soon as a person has more than 145 millimoles per liter of blood serum, then he has hypernatremia, which is too great a concentration of sodium in his blood serum. If a person’s serum sodium level falls below 137 millimoles per liter, then they have hyponatremia, which is too low a concentration of sodium in his blood serum.
