Introduction:
The polyuropolydipsic syndrome is defined by a urinary flow rate greater than 3 l / d (or 2 ml / min) defining polyuria, associated with a parallel increase in oral fluid intake defining polydipsia. The volume of drinks and urine can reach up to 20 l / d and impede the patient in his daily activity or in his sleep.
As long as the hydrous urine inputs and losses compensate each other, which is the most frequent case, the water stock remains adapted to ensure correct cellular hydration: there is no water balance disorder, importance of the polyuropolydipsic syndrome is related to that of losses and intakes. Otherwise, there is a disorder of cellular hydration, which in practice results in a disorder of the natremia, and which can lead to major life-threatening complications. This possibility may arise in two circumstances:
– the increase in diuresis in relation to the limitation of the power of urinary concentration is not compensated by an increase in water intakes due to insensitivity to thirst or an impossibility to satisfy it, resulting in cellular dehydration (hypernatremia);
– limitation of the urine dilution capacity leads to a limitation of diuresis, which is no longer able to compensate for excessive excess intake, causing cell hyperhydration (hyponatremia).
Physiopathology:
It is important to begin by recalling that any chronic polyuria, by decreasing the corticomedullary osmolar gradient, is the cause of a decrease in the power of concentration of the urine.
For a given value of the osmotic load to be excreted, this decrease is itself a factor of increase in diuresis, hence the installation of a veritable vicious circle.
The polyuria can be:
– secondary to an excessive supply of solutes in the collecting tubule: the urine is then concentrated (clearance of negative free water) and we speak of diuresis and osmotic polyuria;
– in relation to an excess of renal elimination of the water, primitive or secondary to an excess of liquid intakes: the urines are then diluted (clearance of the positive free water) and one speaks of aqueous diuresis and polyuria.
OSMOTIC POLYURIE:
Since urine concentration is limited, any urinary excretion of solutes requires urinary excretion of water. The osmotic load to be excreted in the urine is generally less than 900 mosm / d. Since the urinary concentration of a normal kidney reaches 900 to 1,200 mosm / l, 1 l / d of urine may usually suffice. An excessive osmotic load (eg 1500 mosm / d) in theory requires a minimum diuresis of about 1.5 l / d for this value of the concentration power, but in practice a much greater increase: increase in diuresis results in a decrease in the concentration of urine which can be limited to 500 mosm / l. The excretion of the osmotic load (1500 mosm / d) then requires a minimum diuresis of 3 l / d. This explains why urinary osmolality is usually less than the maximum urinary concentration (900-1 200 mosm / l) in osmotic diuresis situations. However, osmotic diuresis and polyuria always correspond to a situation of clearance of negative free water. Polydipsia is secondary to polyuria. The polyuropolydipsic syndrome is all the more important as the capacity of the kidney to concentrate the urine is impaired (tubulopathy, renal insufficiency, …).
A high osmotic load at the collecting tubule may be related to:
– an excessive filtered charge linked to an exogenous contribution (mannitol, sodium, iodinated contrast media, …) or endogenous (hyperosmolar diabetic coma, …) tending to increase the plasma osmolality which will rise if the increase in fluid intake to the stimulation of the centers of thirst fails to prevent this increase;
– insufficient tubular reabsorption due to tubulopathy or drug poisoning (diuretics) tending to decrease the plasma osmolality which is therefore normal or low.
POLYUROPOLYDIPSIC SYNDROMES WITH AQUEOUS DIURESSE:
The aqueous diuresis and polyuria correspond to a situation of clearance of the positive free water. These situations, most often chronic, are responsible for the majority of polyuropolydipsic syndromes. The aqueous polyuria may be primitive or secondary.
Primary aqueous polyuria:
It is related to insufficient reabsorption of water in the collecting tubule responsible for a defect in urine concentration.In this situation, polyuria is primitive and polydipsia, caused by the sensation of thirst, is secondary to polyuria.Polyuria is responsible for a tendency to plasma hypertonia which should normally stimulate antidiuretic hormone (ADH) secretion and prevent polyuria.
We can distinguish: neurogenic diabetes insipidus, linked to a defect (complete form) or to a deficiency (partial form) of ADH secretion; we can compare gestational diabetes insipidus, linked to an increase in the catabolism of ADH (in connection with placental production of aminopeptidase that degrades oxytocin and ADH in vivo and in vitro) and resolving within 3 weeks following childbirth; Nephrogenic diabetes insipidus linked to an insensitivity of the tubule to ADH and whose insipid diabetes can be related to an alteration of the corticomedullary gradient (chronic polyuria, severe malnutrition, interstitial tubulopathy, chronic renal insufficiency, etc.).
Secondary aqueous polyuria:
It is the consequence of excessive fluid intake (polydipsia or excessive hypotonic intravenous infusions) responsible for a tendency to plasma hypotonia which inhibits the secretion of antidiuretic hormone (ADH) and thus causes polyuria. Polyuria is associated with polydipsia only when the fluid is ingested orally. Polydipsia may be associated with an abnormal sensation of thirst (diabetes insipid dipsogen) or not (diabetes insipid psychogenic), the patient thinking then beneficial to increase his water intake. In this situation, polydipsia is primitive and polyuria is secondary to polydipsia.
Diagnostic:
The positive diagnosis of a polyuropolydipsic syndrome is simple and based on interrogation. We must only take care to assert the polyuria by checking the abundance of the urine, so as not to confuse it with a pollakiuria (increased frequency of urination with a normal daily urine volume). Pollakiuria has no reason to be associated with polydipsia.Clinical examination is normal, unless the polyuropolydipsic syndrome is decompensated and then responsible for a hydration disorder. In case of chronic polyuria, an increase in the volume of the bladder and dilation of the urinary tract can be observed. Cerebral magnetic resonance imaging (MRI) provides evidence for central diabetes insipidus when it shows abnormalities in the hypothalamus or posthypophysis.
Etiologic diagnosis is essential in order to be able to propose adapted therapeutics. It is often mentioned on the examination or the clinical context (neurosurgical intervention, recovery of renal function after acute renal failure, …) which make it possible to demonstrate a known cause. For example, polyuria developed in the context of neurosurgical postoperative resuscitation suggests an osmotic polyuria associated with an excessive supply of isotonic or hypertonic solutes (glucose, mannitol) or aqueous polyuria in connection with excessive water intake or hypotonic solutes or in connection with postneurosurgical diabetes insipidus. The discovery of a polyuropolydipsic syndrome in a maniacodepressive treated with lithium salts suggests both the role of polydipsia related to psychiatric illness and that of nephrogenic diabetes insipidus related to lithium tubulopathy and chronic polyuria, remains difficult to highlight the respective shares.
The confirmation of the etiologic diagnosis requires first of all to establish the osmotic character (urinary flow > 50 mosm / h) or aqueous (urinary flow < 50 mosm / h) of the polyuria. Since the urinary osmotic flow is not easy to determine, it is often preferred to assess the urinary osmolality U osm and compare it to the osmolality of the plasma P osm . An osmotic polyuria corresponds to a urinary osmolality greater than 300 mosm / kg or a U osm / P osm ratio greater than 1. The aqueous polyuria corresponds to a urinary osmolality of less than 300 mosm / kg or a U osm / P osm ratio less than 1 (in cases of osmotic diuresis, the urine may not be frankly hypertonic because of the limitation of the urinary concentration power associated with polyuria).
The rest of the diagnostic procedure is based on a pathophysiological approach. In the context of aqueous polyuria, the etiological approach consists in establishing whether polyuria is primary and responsible for polydipsia or whether polydipsia is primitive and responsible for polyuria. This process begins with an assessment of the state of cellular hydration, whose natremia, which is easy to measure and quasi-systematic, is an accurate reflection in aqueous polyuriae situations in which variations in plasma osmolality P osm are related with a variation of the water stock and not of the osmolar stock.
OSMOTIC POLYURIE:
The etiological diagnosis of osmotic polyuria is usually simple because the clinical context and the urinary ionogram generally allow the solute to be easily identified as the source of osmotic diuresis. In practice, we begin by investigating whether the osmotic diuresis is the result of an undissociated substance (glucose, urea, mannitol, …) or of an electrolyte, by comparing the total urinary osmolality U osm with the urinary ionic osmolality U If it is an electrolyte, the determination of the sign of the urinary anionic hole makes it possible to know whether the electrolyte in question is different from sodium and potassium.
AQUEOUS POLYURY ASSOCIATED WITH NATURAL DISORDER:
The disorder of the bloodstream, which indicates a water balance disorder linked to the fact that polyuria and polydipsia are no longer able to compensate, simplifies the diagnostic procedure and renders the dynamic tests (water restriction or chloride perfusion test unnecessary). sodium, exogenous ADH test).
With hyponatremia:
Hyponatremia reflects cellular hyperhydration indicating that excess fluid intake outweighs polyuria, which remains insufficient due to the limitation of dilution. Polyuria is secondary to polydipsia and adapted to hyponatremia.
The ADH test can be dangerous as it aggravates hyponatremia and cellular hyperhydration.
With hypernatremia:
Hypernatremia is more commonly associated with aqueous polyuria than hyponatremia. It reflects cellular dehydration indicating that polyuria outweighs polydipsia. Polyuria is primitive and unsuitable for hypernatremia.
The plasma hyperosmolality reflected by hypernatremia stimulates the centers of thirst, which should normally result in sufficient polydipsia to avoid cellular dehydration. A frank hypernatremia therefore appears only if there is insensitivity to thirst (adipsia, disturbances of consciousness) or an impossibility to satisfy it (water deficiency, handicap, restriction test of water, …) The restriction test hydrous or hypertonic sodium chloride perfusion, completely unnecessary in this context, is dangerous because it aggravates hypernatremia and cell dehydration. The type of diabetes insipidus (neurogenic or nephrogenic) can be specified by the dosage of ADH: ADH is high in case of diabetes insipid nephrogenic and normal or lowered in diabetes insipid neurogenic. This assay, the results of which are generally not immediate, may be replaced by an exogenous ADH test: urinary osmolality rises upright (above 500 mosm / kg) by exogenous ADH infusion in case of diabetes insipid neurogenic, while it does not rise or little in case of nephrogenic diabetes insipidus.
AQUEOUS POLYURIE WITHOUT NATURAL DISORDER:
In most cases, serum sodium levels remain within normal limits due to a correct match between fluid intake and polyuria. The etiological diagnosis of aqueous diuresis is then more difficult and requires to stimulate the secretion of ADH by an increase of the plasma osmolality obtained during a water restriction test or during the perfusion of hypertonic sodium chloride , in order to differentiate polyuria secondary to excess fluid intake and polydipsia secondary to diabetes insipidus.
A clear elevation of U osm (above 500 mosm / kg) is indicative of primary polydipsia while the absence of elevated urinary osmolality (U osm remains below 300 mosm / kg) indicates diabetes insipidus (neurogenic or nephrogenic).
However, the interpretation of this test is often difficult because a moderate increase in urine osmolality under hydric restriction can be observed both in diabetes insipidus (which can lead to moderate U osm elevation if is partial) than in the presence of a primary polydipsia (which may not allow a clear rise in U osm due to the decrease in the polycystic corticopapillary osmolar gradient). The study of the renal response to vasopressin (exogenous ADH test) is then useful: after injection of vasopressin, an increase in urinary osmolality of less than 15% is in favor of a primary polydipsia or an anti- nephrogenic diabetes insipidus easily distinguished by the measurement of the base level of ADH, while an increase of more than 15% is in favor of neurogenic diabetes more or less complete (partial if the increase is between 15 and 50 %, complete if greater than 50%).
Treatment:
TREATMENT OF OSMOTIC POLYURIES:
It rests essentially on that of the cause. On the symptomatic side, it should be taken into account that each liter of urine excreted during an osmotic diuresis contains about 50 mmol of sodium and 25-50 mmol of potassium. Care should be taken to ensure adequate intake to avoid extracellular dehydration and hypokalaemia.
TREATMENT OF AQUEOUS POLYURIES (INSIPID DIABETES):
The treatment of neurogenic diabetes insipidus relies on the replacement therapy with an ADH analog (desmopressin = 1 deamino-8-D-arginine-vasopressin = dDAVP = Minirin t ) nasally (10 to 20 μg 2 to 3 times day) or orally (0.1 to 0.2 mg 3 times daily). If the antidiuretic hormone deficiency is not complete, carbamazepine (200 to 600 mg / d, ie 1 to 3 cp / d of Tegretol t ) can be effective because it seems to potentiate the secretion of ADH.
Gestational diabetes insipidus is effectively treated with dDAVP.
Treatment should be discontinued 1 to 2 weeks after delivery. It does not contraindicate breast-feeding because the dDAVP
passes little into the breast milk and is only slightly absorbed in the digestive tract of the infant.
Diabetes insipidus of nephrogenic origin requires treatment of the cause when it is possible. Inhibitors of prostaglandin synthesis (indomethacin, ibuprofen) generally have some efficacy by allowing an increase in sensitivity to ADH.
The combination of a salt-restricted diet and thiazide diuretics induces a sodal deficiency that causes a contraction of the extracellular volume (loop diuretics are not indicated because they inhibit the establishment of the corticopapillary gradient and decrease the effects of DHA). Contraction of the extracellular volume may reduce polyuria, both in the neurogenic and nephrogenic form of diabetes insipidus.
Amiloride (potassium-sparing diuretic) has also recently been used successfully in some cases of nephrogenic diabetes insipidus, particularly in those associated with lithium intake, as it reduces the effect of lithium on tubular reabsorption (decreasing the re-absorption of lithium in the collecting tube).
No effective treatment of primary polydipsia is known.
The prescription of dDAVP is not logical, because it tends to cause a hydric overload (hyponatremia) secondary to the maintenance of the liquid intake. However, it can improve nocturia if given at bedtime, but the dose necessary and sufficient to decrease nighttime diurnesis while avoiding hyponatremia during the next day is difficult to determine.
The prevention of complications of diabetes insipidus consists in ensuring the mutual compensation of fluid intake and polyuria in order to avoid the appearance of a disorder of the natremia. In the case of aqueous polyuria linked to diabetes insipidus (neurogenic or nephrogenic), it is essential, when the patient does not feel thirsty or unable to drink to his thirst, to compensate for diuresis by the perfusion of isotonic glucose , otherwise cell dehydration (hypernatremia) can rapidly develop, which can quickly threaten the vital prognosis. In the case of aqueous polyuria secondary to water poisoning (hyponatremia), water restriction is logical treatment, but it can be difficult to obtain in a psychiatric context. The addition of a large quantity of osmoles (hypertonic sodium chloride, etc.) offers the possibility of eliminating a larger volume of water for a given value of urinary dilution.
