Polyuria

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ICD-9 788.42

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2] Luke Rusowicz-Orazem, B.S., Roshan Dinparasti Saleh M.D.

To view a comprehensive algorithm of common findings of urine composition and urine output, click here

Overview

Polyuria is the passage of a large volume of urine in a given period (>= 2.5L/24 hours in adult humans). It often appears with increased thirst (polydipsia). Various causes of polyuria include

Causes

  1. Central diabetes inispidus (CDI)
    1. Idiopathic CDI: the most common cause of CDI[1][2]
    2. Familial CDI[3]
    3. Wolfram syndrome ( DIDOMAD syndrome)[4]
    4. Congenital hypopituitarism[5]
    5. Septo-optic dysplasia[6]
    6. Surgery/trauma[7]
    7. Cancer (lung cancer, leukemia, lymphoma)[1]
    8. Hypoxic encephalopathy[8]
    9. Infiltrative disorders ( histiocytosis X, sarcoidosis, granulomatosis with polyangiitis)[9][10]
    10. Post-supraventricular tachycardia[11][12]
    11. Anorexia nervosa[13]
  2. Nephrogenic diabetes inspidous (NDI)
    1. Hereditary NDI[14][15]
    2. Lithium[16]
    3. Hypercalcemia[17][18]
    4. Hypokalemia[19][20]
    5. Renal disease:
      1. Bilateral urinary tract obstruction[21]
      2. Medullary cystic kidney disease[22]
      3. Amyloidosis[23]
      4. Sjogren's syndrome[24]
      5. Autosomal dominant polycystic kidney disease[22]
      6. Sickle cell disease[25]
    6. Medications:
      1. Cidofovir[26]
      2. Foscarnet[27]
      3. Amphotericin B
      4. Demeclocycline
      5. Ifosfamide
      6. Ofloxacin
      7. Orlistat
      8. Didanosine[28]
      9. V2 receptor antagonists[29]
    7. Gestational diabetes insipidus[30][31]
    8. Craniopharyngioma surgery[32]
    9. Bardet-biedl syndrome[33]
    10. Bartter syndrome[34]
    11. Cystinosis[35]
  3. Primary Polydipsia
  4. Osmotic diuresis: Diabetes mellitus

Causes by Organ System

Cardiovascular Cardiorespiratory disease, Circulation, Congestive heart failure, Paroxysmal tachycardia
Chemical/Poisoning 3,3-dichlorobenzidine, Caffeine poisoning, Foscarnet sodium, Frusemide, Juniper tar poisoning, Oak poisoning, Silicon dioxide, Sodium ferrocyanide, Sorbitol
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect Amitraz  , BCG vaccine, Bendrofluazide, Bumetanide, Canagliflozin, Conivaptan, Dapagliflozin, Diuretic therapy, Empagliflozin, Goserelin, Hydrochlorothiazide, Isosorbide, Lithium, Mannitol, Nabilone, Phendimetrazine, Probenecid, Tiagabine, Tolvaptan, corticosteroid
Ear Nose Throat Sicca syndrome
Endocrine Adrenal adenoma, Adrenal cancer, Adrenal cortex neoplasms, Adrenal gland hyperfunction, Aldosteronism, Conn's disease, Cushing syndrome, Cystinosis, DKA, Ectopic ACTH syndrome, Electrolyte abnormality, Familial hypopituitarism, Fanconi syndrome, Froelich's syndrome, Hair-an syndrome, Hormonal, Hyperadrenalism, Hypercalcemia, Hypercalcuria, Hyperglycemia, Hyperosmolar hyperglycemic nonketotic syndrome, Hyperparathyroidism, Hyperthyroidism, Hypokalemia, Hypokalemic periodic paralysis, Hypopituitarism, Hypothalamic dysfunction, Intermediate cystinosis, Multiple endocrine neoplasia, Panhypopituitarism, Parathyroid cancer, Pheochromocytoma, Pituitary tumors, Postural orthostatic tachycardia syndrome, Primary hyperaldosteronism, Syndrome of inappropriate antidiuretic hormone
Environmental Postobstructive uropathy
Gastroenterologic Gestational diabetes, Rib tumor, Wandering spleen
Genetic Aceruloplasminemia, Amelogenesis imperfeca, Apparent mineralocorticoid excess, Bartter syndrome, Boichis syndrome, Conn's disease, Dend syndrome, East syndrome, Gitelman syndrome, Hair-an syndrome, Hereditary primary fanconi disease, Machado-joseph disease, Senior-loken syndrome, Wolfram's disease
Hematologic Diabetes insipidus  , Diabetes mellitus, Excessive riboflavin, Excessive vitamin d, Hemochromatosis  , Hhns, Hypercalcemia, Hypercalcuria  , Hyperglycemia  , Hyperosmolar hyperglycemic nonketotic syndrome  , Hypervitaminosis a, Hypervitaminosis d, Hypokalemia, Hypokalemic periodic paralysis  , Langerhans cell histiocytosis  , Leukemia, Neurosarcoidosis  , Proximal renal tubular acidosis  , Resolving hematoma, Sickle-cell anemia
Iatrogenic Bcg vaccine, Chemotherapy-induced cystitis, Diuretic therapy, Pelvic lipomatosis  , Radiation cystitis, Radiographic contrast media
Infectious Disease Gonococcal urethritis  , Serratia urinary tract infection  , Streptococcal group b invasive disease  , Urinary tract infection
Musculoskeletal/Orthopedic Back tumor  , Hip cancer  , Pyelonephritis, Secondary bone cancer 
Neurologic Adrenocortical carcinoma, Anorexia nervosa, Cerebral salt-wasting syndrome, Diencephalic syndrome, Migraine, Neurologic damage, Neurosarcoidosis, Olivopontocerebellar atrophy type 3, Postural orthostatic tachycardia syndrome, Psychogenic polydipsia, Seizures
Nutritional/Metabolic Aceruloplasminemia, Dend syndrome, Diabetes insipidus, Diabetes mellitus, Diabetic nephropathy, Excessive riboflavin, Excessive vitamin d, Gestational diabetes, Hhns, Hypervitaminosis a, Hypervitaminosis d, Nephrogenic diabetes insipidus, [Renal tubular transport disorders]], Renal tubulopathy
Obstetric/Gynecologic Ovarian cysts, Premenstrual syndrome, Vagina cancer
Oncologic Adrenal adenoma, Adrenal cancer, Adrenal cortex neoplasms, Adrenal incidentaloma, Adrenocortical carcinoma, Back tumor, Bladder cancer, Chemotherapy-induced cystitis, Conn-louis carcinoma, Conn's adenoma, Ectopic ACTHsyndrome, Erdheim-chester disease, Hip cancer, Leukemia, Parathyroid cancer, Pituitary tumors, Prostate cancer, Prostate conditions, Renal cell cancer, Rib tumor, Secondary bone cancer, Urethral cancer, Uterine leiomyoma, Vagina cancer
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric Anorexia nervosa  , Combat stress reaction  , Generalized anxiety disorder, Seizures
Pulmonary Cardiorespiratory disease, East syndrome  , Heerfordt syndrome 
Renal/Electrolyte Acid-base imbalance, Acute tubular necrosis, Aldosteronism, Alsing syndrome  , Altitude diuresis, Apparent mineralocorticoid excess  , Bartter syndrome  , Boichis syndrome  , Cerebral salt-wasting syndrome, Chronic glomerulonephritis, Chronic interstitial nephritis, Chronic kidney disease  , Chronic renal failure, Chronic wasting disease , Cystitis  , Danubian endemic familial nephropathy, Diabetic nephropathy  , Early chronic pyelonephritis, Electrolyte abnormality  , Eosinophilic cystitis, Gitelman syndrome  , Glomerulonephritis  , Interstitial cystitis, Juvenile nephronophthisis  , Medullary cystic kidney disease  , Megalocytic interstitial nephritis  , Membranoproliferative glomerulonephritis , Nephrocalcinosis  , Nephrogenic diabetes insipidus  , Nephrolithiasis , Nephronophthisis, Nephropathic cystinosis  , Oligomeganephronic renal hypoplasia  , Osmotic diuresis, Polycystic kidney disease  , Polydipsia, Primary tubular proximal acidosis  , Proximal renal tubular acidosis  , Proximal tubulopathy, Psychogenic polydipsia, Pyelonephritis, Radiation cystitis, Reflux nephropathy  , Renal cell cancer  , Renal failure, Renal tubular acidosis, Renal tubular transport disorders, Renal tubulopathy , Toni-fanconi syndrome type 1 
Rheumatology/Immunology/Allergy Heerfordt syndrome  , Neurosarcoidosis  , Reiter’s syndrome  , Uterine fibroids 
Sexual No underlying causes
Trauma No underlying causes
Urologic Benign prostatic hyperplasia, Bladder cancer  , Bladder compression, Bladder conditions, Bladder diverticulum, Enlarged prostate  , Noctural polyuria syndrome, Overactive bladder, Pathological water intake, ostobstructive uropathy, rostate cancer, rostate conditions, Sassoon hospital syndrome, Serratia urinary tract infection  rethral cancer , Urethritis  , rinary outflow obstruction, Urinary stones  Urinary tract infection, Uterine fibroids, Uterine leiomyoma 
Miscellaneous No underlying causes

Causes in Alphabetical Order


Differential Diagnosis of Polyuria








 
 
 
 
 
 
 
Polyuria
❑ 24-hour urine volume >3L
❑ 24-hour urine volume >50 ml/kg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Osmolality >300mosmol
 
 
 
 
 
 
 
Urine Osmolality <300[36]mosmol
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solute diuresis
Glucose
Mannitol
Contrast media
High protein intake
Diuretics
Medullary cystic disease
Resolving ATN
Resolving obstruction
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Water diuresis
Primary polydipsia
Diabetes inspidous
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Water restriction test OR administration of hypertonic saline 0.05 mL/kg/min for 2 h
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Water restriction test
❑ Overnight fluid restriction should be avoided
❑ Recommend the patient to stop drinking 2-3 hours before coming to clinic
❑ Meaure urine volume every hour
❑ Measure urine osmolality every hour
❑ Measure plasma sodium concentration every 2 hours
❑ Measure plasma osmolality every 2 hours
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test endpoints in adults:
❑ Urine osmolality reaches normal value (above 600 mosmol/kg)[means that ADH release and effect are intact]
❑ The urine osmolality is stable for 2 or 3 successive hourly measurements despite a rising plasma osmolality
❑ Plasma osmolality >295-300 mosmol/kg
❑ Plasma sodium is 145 or higher
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In the last 3 settings desmopressin 10mcg intranasal, or 4mcg SC/IV is administered
❑ Measure urine volume and urine osmolality every 30 minutes over the next two hours
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>100% rise in urine osmolality
 
15-50% rise in urine osmolality after administration of exogenous desmopressin
 
 
<15% rise in urine osmolality
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete central diabetes inspidous[37]
 
Partial central DI or partial nephrogenic DI[38]
 
 
complete nephrogenic DI or '''primary polydipsia'''
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check plasma and urine ADH[39]and copeptin prior to administration of exogenous ADH
❑ Increase in plasma/urine ADH in response to rising plasma osmolality excludes central DI
❑ Appropriate elevation in urine osmolality as ADH secretion is increased excludes nephrogenic DI
Copeptin > 21.4 picomol/L differentiates Nephrogenic DI from other etiologies with 100% sensivity and specifity[40]
POLYURIA[41]
Mechanism Etiology Clinical manifestations Paraclinical findings Comments
Symptoms and signs Lab findings/Urine exam
Dysuria Nocturia Hesitancy Dribbling Hematuria Proteinuria Serum osmolarity S. ADH Urine osmolarity Water deprivation test ADH administration
Increased intake of fluid Psychogenic polydipsia[42] Normal Normal Low Improves urine osmolarity No improvement Increased thirst
Increased solute excretion Osmotic causes Diabetes mellitus[43] ± Late stage High in type 2 Normal Normal No effect No effect Hyperosmolar hyperglycemic state
Salt loss Diuretics[44][45] + + ± Normal Raised Normal, increased with thiazides No effect No effect
Cerebral salt-wasting syndrome[46] Normal Normal Low Improves urine osmolarity No effect
Impaired urinary concentration Low ADH Central diabetes insipidus + ± ± Increased Low Low No improvement Urine osmolarity improves
Nephrogenic diabetes insipidus + ± ± Increased Normal Low No improvement No improvement
Renal disease Renal tubular acidosis[47][48][49][50] ± ± ± + Increased Raised Normal No effect Increases acidification
Miscellaneous Benign Prostatic Hyperplasia (BPH)[51][52] + + + + ± Normal Normal Normal No effect Improvement

Pathophysiology

Central diabetes inspidus (CDI)

  • Results from a deficiency in production, and release of functional AVP, hence respond to administration of exogenous AVP.[53][54]
  • CDI can be acquired or hereditary. ADH-producing cells' injury in hypothalamus/pituitary can be idiopathic, or due to trauma or infection.
  • Hereditary forms of familial CDI can occur secondary to 66 different mutations of the genes encoding AVP-neurophysin II precursor.[55]

Nephrogenic diabetes insipidus (NDI)

  • It results from an inappropriate renal response to AVP and usually reflects a functional defect in V2R or AQP2 protein.[56]
  • Administration of AVP, therefore is not sufficient to rectify the concentration defect. It is more commonly an acquired disease.[57]
  • Over 225 different mutations in AVPR2 represent almost 90% of hereditary NDI cases.

Diabetes mellitus

Primary polydipsia

  • It is presumed that a central defect in thirst regulation has an important role in pathophysiology of polydipsia.
  • In some polydipsia patients for example, the osmotic threshold for thirst is reduced below the threshold for release of AVP.[59]
  • AVP is suppressed by fall in plasma osmolality(because of excessive water intake), and causes rapid excretion of the excess water and continued stimulation of thirst.[60]

Complications

References

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