Not to be confused with Neurogenic diabetes insipidus.
| Nephrogenic diabetes insipidus |
| Classification and external resources |
| ICD-10 |
N25.1 |
| ICD-9 |
588.1 |
| OMIM |
304800 125800 |
| MedlinePlus |
000511 |
| MeSH |
D018500 |
| GeneReviews |
- Nephrogenic Diabetes Insipidus
|
Nephrogenic diabetes insipidus is a form of diabetes insipidus primarily due to pathology of the kidney. This is in contrast to central/neurogenic diabetes insipidus, which is caused by insufficient levels of antidiuretic hormone (ADH)/Arginine Vasopressin (AVP). Nephrogenic diabetes insipidus is caused by an improper response of the kidney to ADH, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water.
Contents
- 1 Etymology
- 2 Causes
- 2.1 Acquired
- 2.2 Hereditary
- 3 Presentation
- 4 Diagnosis
- 5 Treatment
- 6 References
Etymology[edit]
The name of the disease comes from:
- Diabetes - from L. diabetes, from Gk. diabetes "excessive discharge of urine," lit. "a passer-through, siphon," from diabainein "to pass through," from dia- "through" + bainein "to go"
- Insipidus - "without taste or perceptible flavor," from Fr. insipide, from L.L. inspidus "tasteless," from L. in- "not" + sapidus "tasty," from sapere "have a taste"
This is because patients experience polyuria (an excretion of over 2.5 liters of urine per day), and that the urine content does not have an elevated glucose concentration, as opposed to diabetes mellitus.
Although they shared a name, diabetes mellitus and diabetes insipidus are two entirely separate conditions with a separate pathogenesis. Both cause polyuria (hence the similarity in name) but whereas diabetes insipidus is a problem with the production of antidiuretic hormone (Cranial diabetes insipidus) or renal response to antidiuretic hormone (nephrogenic diabetes insipidus), diabetes mellitus causes polyuria via osmotic diuresis, due to the high blood sugar leaking into the urine, taking excess water along with it.
Causes[edit]
Acquired[edit]
Nephrogenic DI (NDI) is most common in its acquired forms, meaning that the defect was not present at birth. These acquired forms have numerous potential causes. The most obvious cause is a kidney or systemic disorder, including amyloidosis,[1] polycystic kidney disease,[2] electrolyte imbalance,[3][4] or some other kidney defect.[1]
The major causes of acquired NDI that produce clinical symptoms (e.g. polyuria) in the adult are lithium toxicity and hypercalcemia.
Chronic lithium ingestion - appears to affect the tubules by entering the collecting tubule cells through sodium channels, accumulating and interfering with the normal response to ADH (ADH Resistance) in a mechanism that is not yet fully understood.
Hypercalcemia causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium sensing receptor (CaR).
- Osmotic
Other causes of acquired NDI include: hypokalemia, post-obstructive polyuria, sickle cell disease/trait, amyloidosis, Sjogren syndrome, renal cystic disease, Barter syndrome and various drugs (Amphotericin B, Orlistat, Ifosfomide, Ofloxacin, Cidofovir, Vaptanes).
In addition to kidney and systemic disorders, nephrogenic DI can present itself as a side-effect to some medications. The most common and well known of these drugs is lithium,[5] although there are numerous other medications that cause this effect with lesser frequency.[1]
Hereditary[edit]
This form of DI can also be hereditary:
| Type |
OMIM |
Gene |
Locus |
| NDI1 |
304800 |
AVPR2 |
Usually, the hereditary form of nephrogenic DI is the result of an X-linked genetic defect which causes the vasopressin receptor (also called the V2 receptor) in the kidney to not function correctly.[1][6] |
| NDI2 |
125800 |
AQP2 |
In more rare cases, a mutation in the "aquaporin 2" gene impede the normal functionality of the kidney water channel, which results in the kidney being unable to absorb water. This mutation is often inherited in an autosomal recessive manner although dominant mutations are reported from time to time [1][7] |
Presentation[edit]
The clinical manifestation is similar to neurogenic diabetes insipidus, presenting with excessive thirst and excretion of a large amount of dilute urine. Dehydration is common, and incontinence can occur secondary to chronic bladder distension.[8] On investigation, there will be an increased plasma osmolarity and decreased urine osmolarity. As pituitary function is normal, ADH levels are likely to be a normal or raised. Polyuria will continue as long as the patient is able to drink. If the patient is unable to drink and is still unable to concentrate the urine, then hypernatremia will ensue with its neurologic symptoms.[citation needed]
Diagnosis[edit]
Differential diagnosis includes nephrogenic diabetes insipidus, neurogenic/central diabetes insipidus and psychogenic polydipsia. They may be differentiated by using the water deprivation test. Recently, lab assays for ADH are available and can aid in diagnosis.
If able to rehydrate properly, sodium concentration should be nearer to the maximum of the normal range. This, however, is not a diagnostic finding, as it depends on patient hydration.
DDAVP can also be used; if the patient is able to concentrate urine following administration of DDAVP, then the cause of the diabetes insipidus is neurogenic; if no response occurs to DDAVP administration, then the cause is likely to be nephrogenic.
Treatment[edit]
Persons with nephrogenic diabetes insipidus will need to consume enough fluids to equal the amount of urine produced. Correct any underlying cause such as hypercalcemia. The first line of treatment is hydrochlorothiazide and amiloride.[9] Consider a low-salt and low-protein diet.
Thiazide is used in treatment because diabetes insipidus causes the excretion of more water than sodium (i.e. dilute urine). This condition results in a high serum osmolarity (all the retained solutes stay in the serum). This high serum osmolarity stimulates polydipsia in an attempt to dilute the serum back to normal and provide free water for excreting the excess serum solutes. However, since the patient is unable to concentrate urine to excrete the excess solutes, the resulting urine fails to decrease serum osmolarity and the cycle repeats itself, hence polyuria. Thiazide diuretics allow increased excretion of Na+ and water, thereby reducing the serum osmolarity and eliminating volume excess. Basically, Thiazides allow increased solute excretion in the urine, breaking the Polydipsia-Polyuria cycle.
References[edit]
- ^ a b c d e Wildin, Robert (2006). What is NDI?. The Diabetes Inspidus Foundation. http://www.diabetesinsipidus.org/4_types_nephrogenic_di.htm
- ^ http://kidney.niddk.nih.gov/kudiseases/pubs/insipidus/index.htm
- ^ Marples D, Frøkiaer J, Dørup J, Knepper MA, Nielsen S (April 1996). "Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex". J. Clin. Invest. 97 (8): 1960–8. doi:10.1172/JCI118628. PMC 507266. PMID 8621781.
- ^ Carney S, Rayson B, Morgan T (October 1976). "A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia". Pflugers Arch. 366 (1): 11–7. doi:10.1007/BF02486556. PMID 185584.
- ^ Christensen S, Kusano E, Yusufi AN, Murayama N, Dousa TP (June 1985). "Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats". J. Clin. Invest. 75 (6): 1869–79. doi:10.1172/JCI111901. PMC 425543. PMID 2989335.
- ^ Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS, NEPHROGENIC, X-LINKED -304800
- ^ Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS, NEPHROGENIC, AUTOSOMAL -125800
- ^ Kavanagh, Sean (20 Jun 2007). "Nephrogenic Diabetes Insipidus". Patient UK. Retrieved 22 Jun 2009.
- ^ Kirchlechner V, Koller DY, Seidl R, Waldhauser F (June 1999). "Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride". Arch. Dis. Child. 80 (6): 548–52. doi:10.1136/adc.80.6.548. PMC 1717946. PMID 10332005.
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Urinary system · Pathology · Urologic disease / Uropathy (N00–N39, 580–599)
|
|
| Abdominal |
Nephropathy/
(nephritis+
nephrosis) |
Glomerulopathy/
glomerulitis/
(glomerulonephritis+
glomerulonephrosis) |
|
Primarily
nephrotic
|
|
Non-proliferative
|
Minimal change · Focal segmental · Membranous
|
|
|
Proliferative
|
Mesangial proliferative · Endocapillary proliferative · Membranoproliferative/mesangiocapillary
|
|
|
By condition
|
Diabetic · Amyloidosis
|
|
|
|
|
|
Type I RPG/Type II hypersensitivity
|
Goodpasture's syndrome
|
|
|
Type II RPG/Type III hypersensitivity
|
Post-streptococcal · Lupus (DPN) · IgA/Berger's
|
|
|
Type III RPG/Pauci-immune
|
Granulomatosis with polyangiitis (Wegener's) · Microscopic polyangiitis · Churg-Strauss Syndrome
|
|
|
|
|
Tubulopathy/
tubulitis
|
|
Proximal
|
RTA (RTA 2) · Fanconi syndrome
|
|
|
Thick ascending
|
Bartter syndrome
|
|
|
Distal convoluted
|
Gitelman syndrome
|
|
|
Collecting duct
|
Liddle's syndrome · RTA (RTA 1) · Diabetes insipidus (Nephrogenic)
|
|
|
Renal papilla
|
Renal papillary necrosis
|
|
|
Major calyx/pelvis
|
Hydronephrosis · Pyonephrosis · Reflux nephropathy
|
|
|
Any/all
|
Acute tubular necrosis
|
|
|
|
Interstitium
|
Interstitial nephritis (Pyelonephritis, Danubian endemic familial nephropathy)
|
|
|
Any/all
|
|
General syndromes
|
Renal failure (Acute renal failure, Chronic renal failure) · Uremic pericarditis · Uremia
|
|
|
Vascular
|
Renal artery stenosis · Renal Ischemia · Hypertensive nephropathy · Renovascular hypertension · Renal Cortical Necrosis
|
|
|
Other
|
Analgesic nephropathy · Renal osteodystrophy · Nephroptosis · Abderhalden-Kaufmann-Lignac syndrome
|
|
|
|
|
Ureter
|
Ureteritis · Ureterocele · Megaureter
|
|
|
| Pelvic |
|
Bladder
|
Cystitis (Interstitial cystitis, Hunner's ulcer, Trigonitis, Hemorrhagic cystitis) · Neurogenic bladder · Bladder sphincter dyssynergia · Vesicointestinal fistula · Vesicoureteral reflux
|
|
|
Urethra
|
Urethritis (Non-gonococcal urethritis) · Urethral syndrome · Urethral stricture/Meatal stenosis · Urethral caruncle
|
|
|
| Any/all |
Obstructive uropathy · Urinary tract infection · Retroperitoneal fibrosis · Urolithiasis (Bladder stone, Kidney stone, Renal colic) · Malacoplakia · Urinary incontinence (Stress, Urge, Overflow)
|
|
|
|
|
noco/acba/cong/tumr, sysi/epon, urte
|
proc/itvp, drug (G4B), blte, urte
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Sex linkage: X-linked disorders
|
|
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X-linked recessive
|
|
| Immune |
- Chronic granulomatous disease (CYBB)
- Wiskott–Aldrich syndrome
- X-linked severe combined immunodeficiency
- X-linked agammaglobulinemia
- Hyper-IgM syndrome type 1
- IPEX
- X-linked lymphoproliferative disease
- Properdin deficiency
|
|
| Hematologic |
- Haemophilia A
- Haemophilia B
- X-linked sideroblastic anemia
|
|
| Endocrine |
- Androgen insensitivity syndrome/Kennedy disease
- KAL1 Kallmann syndrome
- X-linked adrenal hypoplasia congenita
|
|
| Metabolic |
- Amino acid: Ornithine transcarbamylase deficiency
- Oculocerebrorenal syndrome
- Dyslipidemia: Adrenoleukodystrophy
- Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate dehydrogenase deficiency
- Danon disease/glycogen storage disease Type IIb
- Lipid storage disorder: Fabry's disease
- Mucopolysaccharidosis: Hunter syndrome
- Purine-pyrimidine metabolism: Lesch–Nyhan syndrome
- Mineral: Menkes disease/Occipital horn syndrome
|
|
| Nervous system |
- X-linked mental retardation: Coffin–Lowry syndrome
- MASA syndrome
- X-linked alpha thalassemia mental retardation syndrome
- Siderius X-linked mental retardation syndrome
- Eye disorders: Color blindness (red and green, but not blue)
- Ocular albinism (1)
- Norrie disease
- Choroideremia
- Other: Charcot–Marie–Tooth disease (CMTX2-3)
- Pelizaeus–Merzbacher disease
- SMAX2
|
|
| Skin and related tissue |
- Dyskeratosis congenita
- Hypohidrotic ectodermal dysplasia (EDA)
- X-linked ichthyosis
- X-linked endothelial corneal dystrophy
|
|
| Neuromuscular |
- Becker's muscular dystrophy/Duchenne
- Centronuclear myopathy (MTM1)
- Conradi–Hünermann syndrome
- Emery–Dreifuss muscular dystrophy 1
|
|
| Urologic |
- Alport syndrome
- Dent's disease
- X-linked nephrogenic diabetes insipidus
|
|
| Bone/tooth |
- AMELX Amelogenesis imperfecta
|
|
| No primary system |
- Barth syndrome
- McLeod syndrome
- Smith–Fineman–Myers syndrome
- Simpson–Golabi–Behmel syndrome
- Mohr–Tranebjærg syndrome
- Nasodigitoacoustic syndrome
|
|
|
|
X-linked dominant
|
|
- X-linked hypophosphatemia
- Focal dermal hypoplasia
- Fragile X syndrome
- Aicardi syndrome
- Incontinentia pigmenti
- Rett syndrome
- CHILD syndrome
- Lujan–Fryns syndrome
- Orofaciodigital syndrome 1
- Craniofrontonasal dysplasia
|
|
|
|
Genetic disorder, membrane: cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
|
| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
|
| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
|
| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
|
|
Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley-Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
|
| STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
|
|
| GC |
- GUCY2D (Leber's congenital amaurosis 1)
|
|
|
| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
|
|
| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
|
| Lipid receptor |
- LRP: LRP2 (Donnai-Barrow syndrome)
- LRP4 (Cenani Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
|
|
| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
|
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- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
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