Author: Robertson, Gary
Headaches are usually not a symptom of NDI, but they can develop if dehydration occurs or the patient drinks large amounts of excessively cold water.
Nephrogenic Diabetes Insipidus (NDI) does not cause problems with foot infections. If your grandson has NDI and not diabetes mellitus, his toenails can be clipped like any other child.
Author: Robertson, Gary
NDI symptoms can remit for certain periods and then reappear if the disease or drug that causes them also remits and relapses.
Author: Knoers, Nine
Much of the discomfort experienced by the NDI infant occurs when they become dehydrated and their sodium potassiumlevels are imbalanced. Make sure your physician has determined the proper level and combination of NDI medications and keep your infant adequately hydrated by giving him all the water he needs. This will help your infant be quite comfortable.
Author: Knoers, Nine
If a woman is certain she is an NDI carrier, then, unfortunately, the only certain way of not passing on the NDI gene is to not have children. If a woman is certain she is an NDI carrier and she is pregnant, she can have a prenatal diagnosis to determine if her unborn child is carrying the NDI gene. It is also suggested that the mother seek family counseling to help her prepare for a child born with NDI.
Author: Bichet, Daniel G.
NDI is only one of the four types of diabetes insipidus (DI). The four types of DI are:
- Nephrogenic DI (NDI) caused by the kidneys’ inability to respond to the antidiuretic hormone, arginine vasopressin(AVP).
- Neurogenic or pituitary DI (PDI), caused by a deficiency of or an inability to synthesize or secrete AVP.
- Dispogenic DI (a form of primary polydipsia), caused by a defect in the thirst mechanism that lowers the point at which a person feels thirsty, resulting in excessive water drinking.
- Psychogenic DI (a form of primary polydipsia), caused by a cognitive defect associated with mental illness which leads to compulsive water drinking.
Since the primary symptoms of all four types of DI are the same – polyuria and polydipsia – clinicians diagnose carefully to determine which form of DI their patient has because each type requires different treatment. As Dr. Gary Robertson of Northwestern University Medical School in Chicago, Illinois, USA states in his article, Differential Diagnosis of Polyuria, these four types can be differentiated clinically only when they occur in the patient in their complete and classical form. If the patient should have a mild or incomplete form of DI, then more sophisticated diagnostic approaches are needed.
If a patient has polyuria, he will void more than two liters of urine over a 24-hour period. Further, that urine will be dilute. That is, the amount of osmotically active particles in the urine (e.g. sodium, sugars, etc.) will be small in proportion to the solvent (free water) portion of the urine. This measure is expressed in terms of osmotically active particles per kilogram of urine. In polyuria, the urine will have an osmolality of less than 300 mosmoles/kg.
Once it has been established that the patient is polyuric, and that the polyuria is not caused by diabetes mellitus, then the clinician can proceed with the next diagnostic step. This involves collecting blood and urine samples, then measuring the patient’s plasma and urine osmolality. (Urine and plasma both contain a solute aspect -salts, minerals, sugars, and a solvent aspect – the body water minus the solvents. Osmolality is a measure of concentration derived from the ratio of osmotically active solutes to solvent.) The initial measurement of the patient’s plasma osmolality is taken during a time when the patient has free access to water. Alternatively, the patient’s plasma sodium concentration can be measured under the same conditions. If these measures fall above normal, i.e. if the plasma is excessively concentrated or sodium abnormally high, it is an indicator of either NDI or PDI. The next step is to measure the concentration of AVP in the patient’s plasma and/or the patient’s reaction to a synthetically modified form of AVP called dDAVP.
If the patient shows no or low levels of AVP in his plasma and if he responds to dDAVP with increased urine concentration, this is indicative of PDI. If the patient shows normal to slightly elevated levels of plasma AVP and responds to dDAVP with no increase in urine concentration, it is indicative of NDI. But if the polyuric patient’s initial plasma osmolality and sodium measurements are not above normal, then the clinician and patient must take another step to arrive at a diagnosis.
The patient must undergo a carefully monitored period of no longer than 8 hours where he abstains from water. Note: a shorter dehydration period of 4 hours is indicated if the patient is severely polyuro-polydipsic. Plasma sodium should not be allowed to increase above 150 mEq/L during the dehydration test. During the time of this water fast, the patient’s body weight, urine and plasma (or sodium) osmolalities should be measured hourly. If the patient’s urine does not become more concentrated (i.e. if it does not rise above 300 mosmols/kg) before his plasma or sodium concentrations rise above normal, then the patient does not have primary polydipsia and should be given AVP or dDAVP. If the patient’s urine osmolality increases by more than 50% in response to this, he has PDI. If it does not, he has NDI.
Measuring an NDI patient’s responses to dDAVP in several variables outside the kidney such as heart rate, diastolic blood pressure and facial flushing is one way clinicians have of distinguishing between NDI caused by mutant V2R genes and NDI caused by mutant AQP2 genes. The patient with NDI caused by mutant AQP2 genes will show responses to dDAVP in these variables. The patient whose NDI is the result of mutated V2R genes will not.
Sometimes a polyuric patient’s urine concentration will increase in response to the period of water deprivation. If it does, the patient could have PP, partial PDI or partial NDI. To distinguish which type of DI he may have, the clinician can take one of two approaches:
- He can continue the patient’s water fast until his plasma or sodium osmolality rises above normal, then measure plasma AVP and plasma and urine osmolality.
- If the patient cannot tolerate prolonged water deprivation, he may be given an infusion of hypertonic (3%) saline and an infusion of aqueous Pitressin (a form of vasopressin). Then the patient’s plasma AVP and plasma and urine osmolality can be measured. The clinician can then define more fully the relationship of plasma AVP to plasma or urine osmolality and interpret it in the same way as in the normal dehydration test to determine what form of NDI the patient has.
Author: Bichet, Daniel G.
There is as yet no cure for inherited NDI, though researchers are hopeful that their study of the genetic basis of the disorder will lead to some form of genetic therapy that will cure it. Currently, NDI is managed by:
- ensuring ready access to water,
- following a low-sodium (and sometimes low-protein) diet, and
- using thiazide diuretics, alone or in combination with a prostaglandin inhibitor or a potassium-sparing diuretic, to reduce the volume of urine output.
Thiazide diuretics can reduce an NDI patient’s polyuria, but they may also deplete the body’s stores of potassium. This depletion can cause other symptoms and may be dangerous. When taking thiazide diuretics, the patient’s potassium levels must be monitored. To maintain sufficient potassium in the body, the addition of potassium supplements or amiloride (but not both) to the treatment regime may be required.
Walter Rosenthal and Alexander Oksche of the Forschungsinstitut für Molekulare Pharmakologie in Berlin, Germany state in The Molecular Basis of Nephrogenic Diabetes Insipidus that combining a thiazide (such as hydrochlorothiazide) with a potassium-sparing diuretic (such as amiloride) may be more effective than using a thiazide alone. Sometimes thiazides are used in combination with the prostaglandin inhibitor, indomethacin. Elevated levels of Prostaglandin E2 (PGE2) have been reported in NDI patients, and PGE2 in the kidney interferes with the activity of AVP. Indomethacin inhibits the synthesis of prostaglandin in the kidney, thus reducing polyuria in cases of both inherited and acquired NDI. However, Bichet recommends using a prostaglandin inhibitor only in an emergency situation and then only for a short time. Rosenthal and Oksche mention that the combination of thiazides and amiloride may be preferable because they have less potential side effects than a combination of indomethacin and thiazide. Indomethacin, a non steroidal anti-inflammatory agent, often causes headaches and dizziness, or an increased risk of gastrointestinal disorders. Also, if administered in the first year of life, indomethacin increases the risk of kidney disease.
Thiazide diuretics should be used with care in cases of lithium-induced NDI as they reduce the degree to which the kidney can excrete lithium, thereby setting the stage for a toxic build-up of lithium. Amiloride is more widely used in these cases as it inhibits the accumulation of lithium while blunting lithium’s inhibiting action of water reabsorption. In The Management of Diabetes Insipidus in Adults, Dr. Irwin Singer of the Veterans Affairs Medical Center in Miami, Florida, USA, et al., notes that while thiazides rob the body of potassium, amiloride inhibits excretion of potassium in the urine. Dr. Patricia Adams from Smiley’s Clinic in Minneapolis, Minnesota, USA states in Evaluation and Management of Diabetes Insipidus that thiazide diuretics and amiloride deplete total body salt, which allows the kidneys to more readily absorb water. However, this improved water absorption is negated by a diet heavy in salt, so low-sodium diets such as that recommended in Diet and Nutrition by Cristine Trahms and Beth Ogata of the University of Washington in Seattle, Washington, USA are prescribed for NDI patients.
A couple of other pharmacalogical management tools have shown some, though variable, results. Burke, et al., in a case report in Critical Care Medicine found that a patient with lithium-induced NDI showed a dramatic increase in urine osmolality along with a significant decrease in urine output after the patient was treated with ketorolac, a non-steroidal anti-inflammatory agent. However, the long-term effects of this drug as used for this purpose are unknown. Weinstock and Moses in Desmopressin and Indomethecin Therapy for NDI in Patients Receiving Lithium Carbonate, report that some patients can have a partial reduction in urine output in response to large doses of dDAVP. However, other patients in the same condition did not.
Author: Knoers, Nine
When NDI is first diagnosed, the patient will need to see his doctor frequently (2 to 4 times a year) in order to ensure the medications given help the patient achieve the necessary fluid balance. After 6 to 8 years, children whose NDI is in balance, will need to be seen by the doctor once a year. Of course, if the patient isn’t growing well or if his fluid balanceisn’t being maintained or if the medication isn’t working as the patient or his parents expect, then their doctor should be consulted. The patient should also have an ultrasound for his bladder every year in order to see whether or not the bladder has extended beyond its normal form.
Author: Knoers, Nine
Examining your family history could reveal whether or not you carry an NDI causing gene. The most common form of inherited NDI is called X-linked NDI and is passed from mother to son. If that mother has a brother or a maternal uncle with NDI, then she can be sure that she is a carrier because her family history shows an X-linked inheritance pattern. However, there are many cases where a mother has a son with NDI, and there is no family history of this disorder. In this case the mother would need genetic screening to know whether or not she is a carrier. Doctors with extensive experience in screening for the NDI gene include Dr. Robert Wildin in the United States, Dr. Daniel Bichet in Canada, Dr. Nine Knoers in Nijmegen, The Netherlands.
Author: Wildin, Robert
Most patients with NDI have normal thirst mechanisms. They can prevent substantial increases in blood sodium by drinking sufficient water, which most can, although many run slightly high sodium levels anyway. Rarely, patients with NDI who have had severe hypernatremic dehydration may have damaged their thirst center in the brain, and may have problems regulating their own water intake. More commonly, the problem with drinking enough water is simply access. Infants in a crib cannot freely access water, no matter how thirsty, unless they are provided with water bottles. Similarly, our society frequently runs on a regimental schedule that assumes water breaks do not need to occur frequently. Education and accommodation are the best solutions to those problems.
Author: Robertson, Gary
I know of no link between echineacea and NDI or abnormal ADH levels.
Author: Robertson, Gary
In general, if a patient with CNDI has to be deprived of oral fluids because of general anesthesia, dehydration can and should be prevented by giving the necessary amount of water intravenously until the patient regains consciousness and is able to resume taking all the fluids he needs by mouth. If the dental work interferes with drinking, the IV fluids may need to be maintained for longer periods. Therapy to reduce his DI also should be continued to minimize the amount of fluid that must be given intravenously.
Depression, memory lapses and fits of rage are not a direct result of any type of DI. However, they might be an indirect result of dehydration and brain damage caused by DI during infancy. From the other symptoms you describe, your son probably does have some form of DI although it may be partial and less severe than most. Since he has a cousin on his father’s side who has documented pituitary DI, your son probably has the same type of DI on a genetic basis. If so, the genetic mutation is unique since neither of the brothers with affected sons has obvious signs or symptoms of DI. I would recommend that your son be evaluated to determine if he has pituitary DI. If he does, he should start appropriate treatment and, along with his cousin and other relatives, have a genetic analysis to try to identify or at least localize the mutation responsible.
The bladder, and sometimes the ureters, enlarge because they are continually stretched by the high urine output. This problem may be worsened by consciously suppressing the urge to void (“holding it”) in order to diminish urinaryfrequency. The best way to reduce this problem is to:
- employ the dietary and drug treatments to reduce the volume of urine produced, and
- void as often as possible to minimize the volume of urine held in the bladder.
In some cases with severe stretching and loss of bladder tone, self-catheterization once or twice a day may also be necessary. Rarely, it is necessary to surgically implant a catheter in the bladder.
Author: Robertson, Gary
The normal range for serum sodium concentration can differ slightly in different laboratories if they use different methods to measure it. However, the differences should be small.
Author: Bichet, Daniel G.
The incidence of hypertension is not increased in NDI patients as compared to the general population.
Author: Knoers, Nine
Once an infant with NDI is taking the proper medication and can stay hydrated, they should not vomit due to NDI related concerns. Untreated or undiagnosed, infants with NDI vomit because they have imbalanced sodium and potassiumlevels. When this is addressed and the baby is adequately hydrated, he or she should stop vomiting.
