Juan Andrés Oddino and Dr. Fabio Rubén Acosta


For the mean of the word is not easy to find a clear definition. Etymologically it means "a lot of urine output", although there is no consensus on the cut-off point (2.5 / 3 L dia) or if there is inadequate urinary concentration after water restriction or dehydration.

Halperin defines it as "greater than expected urine output." Another definition refers to an inappropriately high urine volume for a patient's balance, which may or may not be reversed with hydrosaline deprivation.

The volume of urine depends on the liquid ingested, on the water necessary to excrete the solutes resulting from the metabolism and on the renal capacity to dilute and concentrate, on the other hand, the distribution of body water depends on the osmolarity. In the normal state, the volume and osmolarity of organic liquids are regulated with an extraordinary degree of precision.

The metabolism of water and sodium, although they have different regulatory mechanisms, have a common effector in the kidney. Thirst adjusts water intake and the kidney regulates its excretion through the concentration / dilution mechanism mediated by the countercurrent system and vasopressin. Sodium homeostasis is more complex and its excretion is regulated by the kidney through neurohormonal and intra kidney.

Polyuria is a consequence of the alteration of one or more processes: 

  • Alteration of the countercurrent mechanism
  • Expansion of effective artery volume.


The urine concentration/dilution process is carried out through a countercurrent multiplier system (Fig. 1), which for the purposes of its understanding  could be divided into:

1- Generation of the interstitial tubule osmotic gradient: Three processes participate: 

  • Magnitude of the fluid derived from the Proximal Contorneated Tubule (PCT) where 75% of the water and filtered sodium are reabsorbed iso osmotically. The presence of an osmotic solute (mannitol, glycerol, glucose) or altered sodium management (acetazolamide, ATR type 2) produces a greater diversion of tubular fluid to the distal sectors, this being one of the generating causes of polyuria. 
  • Water solute separation (diluent segment): 25% of the filtered sodium is reabsorbed in the ascending loop of Henle. The tubular interstitial osmotic gradient is generated in the thick portion by active resorption. Inhibition of this mechanism (loop diuretics, interstitial nephropathies, Bartter syndrome), leads to a high concentration of ClNa in the distal sectors, and consequently a drop in interstitial osmolarity, altering the urinary concentration mechanism. 
  • Urea kinetics: The Distal Contorneated Tubule  (TCD) fluid is always hypotonic (100-150 mOsm), when it reaches the end of the TCC it rises to 300 mOsm (isotonic). A 2/3 reduction in the volume of the tubular fluid prevents it from being exceeded the limited resorption capacity of the medullary collecting tube. At this level urea is concentrated due to its impermeability. One of the causes of polyuria is precisely the alteration of one or both segments (thiazide diuretics, Gitelman syndrome, less secretion or resistance to aldosterone). In the medullary collecting tube, urine reaches its maximum osmolarity (1200 mOsm) or minimum (50mOsm) according to the initial osmolarity and the ADH level.The concentrated urea diffuses by gradient to the insert and recirculates through the loop of Henle. In a stable situation, urea represents 50% of the intra-osmolarity,

2- Maintenance of the gradient: the interstitial osmolarity is maintained by the straight vessels, which have an anatomical loop arrangement and a countercurrent process similar to that of the tubules, variations in blood flow modify their value.

3- Use of the gradient: The Antidiuretic Hormone (ADH) is synthesized by the supraoptic and paraventricular nuclei of the hypothalamus. Alterations in any of these centers generate polyuria (central diabetes insipidus). ADH enters the general circulation via the cavernous sinus-superior vena cava, its blood half-life is short (15 min), there are situations where it is rapidly reduced due to the degrading action of a vasopressinase (diabetes insipidus of pregnancy). In the kidney, ADH binds to V2 receptors in the basolateral membrane of the main collector cells, activating the water channels via cAMP. These receptors, proteins synthesized in the endoplasmic reticulum, are called aquaporins. Different subtypes have been described in different organs. In the kidney AQP?????? 1, 2, 3 and 4. AQP2 is the main target of the hormone and is responsible for regulating the entry of water into the cell. From 3 to 6% is excreted in urine where it can be quantified. AQP 3 and 4 are related to the outflow of water in the basolateral membrane. ADH exerts double regulation, one fast (it accelerates the transport of AQP 2 towards its site of action in the luminal membrane) and the other with a sustained effect (it increases AQP synthesis).

Alterations in some of these steps is also a cause of polyuria (nephrogenic diabetes insipidus).


The main afferents for the regulation of extracellular volume are found in the arterial sector, census the variations of the effective arterial volume.

The expansion generates responses that increase the excretion of water and salt, and the kidney sets in motion counterregulatory mechanisms to prevent an exaggerated excretion of sodium.

The pressure-natriuresis phenomenon whose signal is not properly clarified, is one of the most important intrarenal responses with the participation of the quinine-kallikrein system and its nitric oxide and prostaglandin effectors. The expansion also specifically affects the resorption of water, clearly demonstrated in the syndrome of inadequate secretion of ADH, called vasopressin leakage.

Endogenous or exogenous expansion of effective arterial volume is a cause of polyuria.


Any alteration of the mechanisms involved in urinary concentration can lead to clinical pictures of polyuria. Two large groups are distinguished (Table 1): polyuria with low plasma levels of ADH and that with normal levels of ADH.

The first includes Central or Neurogenic Diabetes Insipidus (DIC), where the synthesis or insufficient secretion of ADH limits the maximum urinary concentration and, depending on the intensity of the disease, produces variable degrees of polyuria and polydipsia; This is classified as primary or secondary, depending on the existence or not of underlying pathological processes. The primary ones are possibly due to an autoimmune injury of the ADH-producing cells in the pituitary and among the secondary ones, the most frequent causes are slow growing tumors like craniopharyngioma; Other secondary causes are intraoperative or postoperative complications of neurosurgical procedures in the hypothalamic pituitary area. Secondary forms can be accompanied by other hypothalamic symptoms such as obesity, precocious puberty,

Primary polydipsia, also called psychogenic polydipsia, is characterized by an increased intake of water, greater than that necessary to maintain the water balance, thus producing a physiological suppression of ADH, due to overhydration and hypotonia, leading to polyuria. This polyuria usually decreases at night, since the polydipsia stops while they sleep. It generally occurs in adolescent female patients and in psychiatric patients. This group includes those who take Phenothiazide, which produces a dry mouth sensation. Another cause is hypothalamic lesions that directly affect the thirst center, as occurs in infiltrative diseases.

Polyuria evaluation: it is convenient to consider:

-appearance circumstances: interrogation.

-hydrosaline balance: background.

-hemodynamic impact: clinical examination.

-Plasmatic icon: indicative of DI in hypernatremia with hypotonic urine, to primary polydipsia in hyponatremia with hypotonic urine. Kalemia disorders point to SARS, as do acidobase balance disorders.

-The composition of the urine allows characterizing polyuria as osmotic or hydric based on osmolarity

Non-osmotic polyuria:

The challenge is to differentiate primary polydipsia from central and nephrogenic DI in its complete or partial forms. If the natremia is normal or low, the water deprivation test is performed (Fig 2) and then the administration of ADH; if it is elevated, the latter is administered directly.

An attempt can be made to measure the plasma concentration of ADH and correlate it with urinary osmolarity in the prepared nomograms.

The dosage of urinary AQP2 is important in the diagnosis different from polydipsia polyuria, since the urinary concentration of aquaporins rises when the patient sleeps

Osmotic polyuria:

Eliminated solutes and the participation of measurable ones must be quantified. Under normal conditions, 600-900 mOsm / day is eliminated, which corresponds mostly to urea. Ideally they should be measured with an osmometer, although it can be calculated based on the concentration of urea and sodium.

Bicarbonaturia is suspected in alkaline urinary pH and can be dosed in urine collected under anaerobic conditions to avoid dissipation of CO2.

The measurement of the osmolar gap in plasma allows the detection of solutes not considered in the estimation of osmolarity (measured osm - calculated osm). The value is <10 mOsm and is useful when symptoms of acid or alcohol poisoning are suspected.

The NICTURIA (evacuation overnight) is a symptom abnormal but nonspecific may reflect incipient kidney disease, with reduced ability to concentrate, but often associated heart and liver failure without evidence of intrinsic renal disease.

NOCTURIA  is the excretion of a nocturnal urinary volume superior to the diurnal one (Fig 3). The prevalence of nocturia increases with old age and predominates in the shoulders over women. It occurs fundamentally in some pathologies such as advanced pregnancy, heart failure (Quincke's Sme), nephrotic syndrome and venous insufficiency.

Risk factors for nocturia include: obesity, hypertension, use of diuretics, snoring, restless leg syndrome, benign prostatic hypertrophy, prostate cancer, use of antidepressants, coronary insufficiency, congestive heart failure, and diabetes.

With low plastmatic levels of ADH (sensitive to ADH)

  • Central diabetes insipidus
    • Primary: hereditary or idiopathic
    • High school:
      • Intracranial tumors: Craniopharyngioma, Chromophobe adenoma, Optic glioma, Melanoma, Metastatic tumors.
      • Post neurosurgery
      • Traumatic brain injury, Skull base fracture
      • Infections: encephalitis, meningitis, Guillian-Barré syndrome, xanthoma.
      • Others: Thrombosis, Aneurysms, IItraventricular hemorrhage and  Perinatal asphyxia (Hans Schuller-Cristian disease), Acute leukemia, Degenerative disease (Laurence-Moon Biedl syndrome)
      • Primary polydipsia, Physiological suppression of ADH.

With adequate plasma levels of ADH (resistant to ADH)

  • Osmotic diuresis:
    • Diabetes insipidus
    • Chronic renal insufficiency
    • Post-obstructive polyuria
    • Polyuric phase of Acute Renal Failure
    • Medicines and other substances such as Mannitol, Glycerol, Radiological contrast media.
  • Nephrogenic diabetes insipidus
    • Primary or hereditary:
      • X-linked recessive
      • Autosomal recessive
    • Secondary or acquired:
      • Primary interstitial tubule nephropathies:
        • Nephronoptisis (medullary cystic disease)
        • Poycystic kidney
        • Hydronephrosis
        • Amyloidosis
        • Acidosis tubular distal
        • Cystinosis and other causes of Fanconi syndrome
        • Idiopathic hypercalciuria
      • Secondary interstitial tubule nephropathies:
        • Caliphenic nephropathy
        • Hypercalcemia: hyperparathyroidism, vitamin D poisoning, sickle cell anemia.
        • Medicinal agents Lithium carbonate, Methoxyfluane, Amphotericin B, Phenacetin, Diclofenac (DANE), Dimethylchlorotetracycline, Diphenylhydantoin.