How is NDI diagnosed?
|Author:||Bichet, Daniel G.|
- 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.