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Tubulointerstitial kidney disease, autosomal dominant, 2(ADTKD2)

MedGen UID:
358137
Concept ID:
C1868139
Disease or Syndrome
Synonyms: ADTKD2; Medullary cystic kidney disease 1; Medullary cystic kidney disease, autosomal dominant; Polycystic kidneys, medullary type
SNOMED CT: Autosomal dominant medullary cystic kidney disease without hyperuricemia (726017001); Medullary cystic kidney disease 1 (726017001); MUC1-related autosomal dominant tubulointerstitial kidney disease (726017001); Mucin 1 related autosomal dominant tubulointerstitial kidney disease (726017001)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): MUC1 (1q22)
 
Monarch Initiative: MONDO:0020726
OMIM®: 174000
Orphanet: ORPHA88949

Disease characteristics

Autosomal dominant tubulointerstitial kidney disease – MUC1 (ADTKD-MUC1) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations. [from GeneReviews]
Authors:
Anthony J Bleyer  |  Martina Živná  |  Kendrah Kidd, et. al.   view full author information

Additional descriptions

From OMIM
Autosomal dominant tubulointerstitial kidney disease-2 (ADTKD2) is characterized by adult onset of impaired renal function and salt wasting resulting in chronic renal insufficiency and end-stage renal failure by the sixth decade. Renal biopsy shows tubulointerstitial nephropathy, sometimes with the formation of renal cysts at the corticomedullary junction, although cysts are not pathognomonic for the disease and are not an essential criterion for the diagnosis. More variable features may include anemia, hypertension, hyperuricemia, and gout; urinary sediment is bland. The features are nonspecific and there is significant inter- and intrafamilial variability, as well as incomplete penetrance, which may hinder the clinical diagnosis (summary by Stavrou et al., 2002, Wolf et al., 2004; review by Devuyst et al., 2019). For a discussion of genetic heterogeneity of ADTKD and a discussion of the revised nomenclature of these disorders, see ADTKD1 (162000).  http://www.omim.org/entry/174000
From MedlinePlus Genetics
Medullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the kidneys. It leads to scarring (fibrosis) and impaired function of the kidneys, usually beginning in adulthood. The kidneys filter fluid and waste products from the body. They also reabsorb needed nutrients and release them back into the blood. As MCKD1 progresses, the kidneys are less able to function, resulting in kidney failure.

Declining kidney function in people with MCKD1 leads to the signs and symptoms of the condition. The features are variable, even among members of the same family. Many individuals with MCKD1 develop high blood pressure (hypertension), especially as kidney function worsens. Some develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. In a small number of affected individuals, the buildup of this waste product can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints.

Although the condition is named medullary cystic kidney disease, only about 40 percent of affected individuals have medullary cysts, which are fluid filled pockets found in a particular region of the kidney. When present, the cysts are usually found in the inner part of the kidney (the medullary region) or the border between the inner and outer parts (corticomedullary region). These cysts are visible by tests such as ultrasound or CT scan.  https://medlineplus.gov/genetics/condition/medullary-cystic-kidney-disease-type-1

Clinical features

From HPO
Interstitial nephritis
MedGen UID:
11952
Concept ID:
C0041349
Disease or Syndrome
A form of inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
Glomerular sclerosis
MedGen UID:
61248
Concept ID:
C0178664
Disease or Syndrome
Accumulation of scar tissue within the glomerulus.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Decreased glomerular filtration rate
MedGen UID:
163428
Concept ID:
C0853068
Finding
An abnormal reduction in the volume of fluid filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time.
Renal salt wasting
MedGen UID:
375868
Concept ID:
C1846347
Finding
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
Renal tubular atrophy
MedGen UID:
388054
Concept ID:
C1858395
Finding
The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.
Tubular basement membrane disintegration
MedGen UID:
368847
Concept ID:
C1968618
Finding
DIsruption and breaking up of the basement membrane of the tubules of the kidney.
Renal corticomedullary cysts
MedGen UID:
409631
Concept ID:
C1968619
Disease or Syndrome
The presence of multiple cysts at the border between the renal cortex and medulla.
Impaired renal uric acid clearance
MedGen UID:
409813
Concept ID:
C1969371
Finding
A reduction in the ability of the kidneys to remove uric acid from the serum.
Tubulointerstitial fibrosis
MedGen UID:
370652
Concept ID:
C1969372
Disease or Syndrome
A progressive detrimental connective tissue deposition (fibrosis) on the kidney parenchyma involving the tubules and interstitial tissue of the kidney. Tubulointerstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal interstitial fibrosis and tubular atrophy (IF/TA) as the final common pathway. However, IF and TA are separable, as shown by the profound TA in renal artery stenosis, which characteristically has little or no fibrosis (or inflammation). For new annotations it is preferable to annotate to the specific HPO terms for Renal interstitial fibrosis and/or Renal tubular atrophy.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Renal cortical atrophy
MedGen UID:
871246
Concept ID:
C4025730
Disease or Syndrome
Atrophy of the cortex of the kidney.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Hypotension
MedGen UID:
5715
Concept ID:
C0020649
Finding
Low Blood Pressure, vascular hypotension.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Gout
MedGen UID:
42280
Concept ID:
C0018099
Disease or Syndrome
Recurrent attacks of acute inflammatory arthritis of a joint or set of joints caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTubulointerstitial kidney disease, autosomal dominant, 2

Professional guidelines

PubMed

Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O; Kidney Disease: Improving Global Outcomes
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250

Recent clinical studies

Etiology

Lemoine H, Raud L, Foulquier F, Sayer JA, Lambert B, Olinger E, Lefèvre S, Knebelmann B, Harris PC, Trouvé P, Desprès A, Duneau G, Matignon M, Poyet A, Jourde-Chiche N, Guerrot D, Lemoine S, Seret G, Barroso-Gil M, Bingham C, Gilbert R; Genomics England Research Consortium; Genkyst Study Group, Le Meur Y, Audrézet MP, Cornec-Le Gall E
Am J Hum Genet 2022 Aug 4;109(8):1484-1499. Epub 2022 Jul 26 doi: 10.1016/j.ajhg.2022.06.013. PMID: 35896117Free PMC Article
Cormican S, Kennedy C, Connaughton DM, O'Kelly P, Murray S, Živná M, Kmoch S, Fennelly NK, Benson KA, Conlon ET, Cavalleri GL, Foley C, Doyle B, Dorman A, Little MA, Lavin P, Kidd K, Bleyer AJ, Conlon PJ
Clin Transplant 2020 Feb;34(2):e13783. Epub 2020 Feb 5 doi: 10.1111/ctr.13783. PMID: 31958169
Park SJ, Kim Y, Chen YM
Pediatr Nephrol 2019 Sep;34(9):1493-1500. Epub 2018 Aug 11 doi: 10.1007/s00467-018-4031-2. PMID: 30099615Free PMC Article
Ayasreh N, Bullich G, Miquel R, Furlano M, Ruiz P, Lorente L, Valero O, García-González MA, Arhda N, Garin I, Martínez V, Pérez-Gómez V, Fulladosa X, Arroyo D, Martínez-Vea A, Espinosa M, Ballarín J, Ars E, Torra R
Am J Kidney Dis 2018 Sep;72(3):411-418. Epub 2018 May 18 doi: 10.1053/j.ajkd.2018.03.019. PMID: 29784615
Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O; Kidney Disease: Improving Global Outcomes
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250

Diagnosis

Wopperer FJ, Knaup KX, Stanzick KJ, Schneider K, Jobst-Schwan T, Ekici AB, Uebe S, Wenzel A, Schliep S, Schürfeld C, Seitz R, Bernhardt W, Gödel M, Wiesener A, Popp B, Stark KJ, Gröne HJ, Friedrich B, Weiß M, Basic-Jukic N, Schiffer M, Schröppel B, Huettel B, Beck BB; Genomics England Research Consortium, Sayer JA, Ziegler C, Büttner-Herold M, Amann K, Heid IM, Reis A, Pasutto F, Wiesener MS
Kidney Int 2022 Aug;102(2):405-420. Epub 2022 May 26 doi: 10.1016/j.kint.2022.04.031. PMID: 35643372
Olinger E, Hofmann P, Kidd K, Dufour I, Belge H, Schaeffer C, Kipp A, Bonny O, Deltas C, Demoulin N, Fehr T, Fuster DG, Gale DP, Goffin E, Hodaňová K, Huynh-Do U, Kistler A, Morelle J, Papagregoriou G, Pirson Y, Sandford R, Sayer JA, Torra R, Venzin C, Venzin R, Vogt B, Živná M, Greka A, Dahan K, Rampoldi L, Kmoch S, Bleyer AJ Sr, Devuyst O
Kidney Int 2020 Sep;98(3):717-731. Epub 2020 May 22 doi: 10.1016/j.kint.2020.04.038. PMID: 32450155
Ayasreh N, Bullich G, Miquel R, Furlano M, Ruiz P, Lorente L, Valero O, García-González MA, Arhda N, Garin I, Martínez V, Pérez-Gómez V, Fulladosa X, Arroyo D, Martínez-Vea A, Espinosa M, Ballarín J, Ars E, Torra R
Am J Kidney Dis 2018 Sep;72(3):411-418. Epub 2018 May 18 doi: 10.1053/j.ajkd.2018.03.019. PMID: 29784615
Bleyer AJ, Kidd K, Živná M, Kmoch S
Adv Chronic Kidney Dis 2017 Mar;24(2):86-93. doi: 10.1053/j.ackd.2016.11.012. PMID: 28284384Free PMC Article
Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O; Kidney Disease: Improving Global Outcomes
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250

Therapy

Tao T, Yang Y, Hu Z
Medicine (Baltimore) 2020 Jul 31;99(31):e21438. doi: 10.1097/MD.0000000000021438. PMID: 32756155Free PMC Article
Vikrant S
Saudi J Kidney Dis Transpl 2019 Mar-Apr;30(2):470-477. doi: 10.4103/1319-2442.256854. PMID: 31031383
Venkat-Raman G, Gast C, Marinaki A, Fairbanks L
Pediatr Nephrol 2016 Nov;31(11):2035-42. Epub 2016 Feb 12 doi: 10.1007/s00467-015-3308-y. PMID: 26872483
Labriola L, Olinger E, Belge H, Pirson Y, Dahan K, Devuyst O
Nephrol Dial Transplant 2015 Feb;30(2):330-5. Epub 2014 Dec 23 doi: 10.1093/ndt/gfu389. PMID: 25540096
Vylet'al P, Hůlková H, Zivná M, Berná L, Novák P, Elleder M, Kmoch S
J Inherit Metab Dis 2008 Aug;31(4):508-17. Epub 2008 Jul 27 doi: 10.1007/s10545-008-0900-3. PMID: 18651238

Prognosis

Kmochová T, Kidd KO, Orr A, Hnízda A, Hartmannová H, Hodaňová K, Vyleťal P, Naušová K, Brinsa V, Trešlová H, Sovová J, Barešová V, Svojšová K, Vrbacká A, Stránecký V, Robins VC, Taylor A, Martin L, Rivas-Chavez A, Payne R, Bleyer HA, Williams A, Rennke HG, Weins A, Short PJ, Agrawal V, Storsley LJ, Waikar SS, McPhail ED, Dasari S, Leung N, Hewlett T, Yorke J, Gaston D, Geldenhuys L, Samuels M, Levine AP, West M, Hůlková H, Pompach P, Novák P, Weinberg RB, Bedard K, Živná M, Sikora J, Bleyer AJ Sr, Kmoch S
Kidney Int 2024 Apr;105(4):799-811. Epub 2023 Dec 12 doi: 10.1016/j.kint.2023.11.021. PMID: 38096951
Olinger E, Hofmann P, Kidd K, Dufour I, Belge H, Schaeffer C, Kipp A, Bonny O, Deltas C, Demoulin N, Fehr T, Fuster DG, Gale DP, Goffin E, Hodaňová K, Huynh-Do U, Kistler A, Morelle J, Papagregoriou G, Pirson Y, Sandford R, Sayer JA, Torra R, Venzin C, Venzin R, Vogt B, Živná M, Greka A, Dahan K, Rampoldi L, Kmoch S, Bleyer AJ Sr, Devuyst O
Kidney Int 2020 Sep;98(3):717-731. Epub 2020 May 22 doi: 10.1016/j.kint.2020.04.038. PMID: 32450155
Ayasreh N, Bullich G, Miquel R, Furlano M, Ruiz P, Lorente L, Valero O, García-González MA, Arhda N, Garin I, Martínez V, Pérez-Gómez V, Fulladosa X, Arroyo D, Martínez-Vea A, Espinosa M, Ballarín J, Ars E, Torra R
Am J Kidney Dis 2018 Sep;72(3):411-418. Epub 2018 May 18 doi: 10.1053/j.ajkd.2018.03.019. PMID: 29784615
Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O; Kidney Disease: Improving Global Outcomes
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250
Norman J
Biochim Biophys Acta 2011 Oct;1812(10):1327-36. Epub 2011 Jul 1 doi: 10.1016/j.bbadis.2011.06.012. PMID: 21745567Free PMC Article

Clinical prediction guides

Kmochová T, Kidd KO, Orr A, Hnízda A, Hartmannová H, Hodaňová K, Vyleťal P, Naušová K, Brinsa V, Trešlová H, Sovová J, Barešová V, Svojšová K, Vrbacká A, Stránecký V, Robins VC, Taylor A, Martin L, Rivas-Chavez A, Payne R, Bleyer HA, Williams A, Rennke HG, Weins A, Short PJ, Agrawal V, Storsley LJ, Waikar SS, McPhail ED, Dasari S, Leung N, Hewlett T, Yorke J, Gaston D, Geldenhuys L, Samuels M, Levine AP, West M, Hůlková H, Pompach P, Novák P, Weinberg RB, Bedard K, Živná M, Sikora J, Bleyer AJ Sr, Kmoch S
Kidney Int 2024 Apr;105(4):799-811. Epub 2023 Dec 12 doi: 10.1016/j.kint.2023.11.021. PMID: 38096951
Olinger E, Hofmann P, Kidd K, Dufour I, Belge H, Schaeffer C, Kipp A, Bonny O, Deltas C, Demoulin N, Fehr T, Fuster DG, Gale DP, Goffin E, Hodaňová K, Huynh-Do U, Kistler A, Morelle J, Papagregoriou G, Pirson Y, Sandford R, Sayer JA, Torra R, Venzin C, Venzin R, Vogt B, Živná M, Greka A, Dahan K, Rampoldi L, Kmoch S, Bleyer AJ Sr, Devuyst O
Kidney Int 2020 Sep;98(3):717-731. Epub 2020 May 22 doi: 10.1016/j.kint.2020.04.038. PMID: 32450155
Bleyer AJ, Kidd K, Johnson E, Robins V, Martin L, Taylor A, Pinder AJ, Bowline I, Frankova V, Živná M, Taylor KB, Kim N, Baek JJ, Hartmannová H, Hodaňová K, Vyleťal P, Votruba M, Kmoch S
Clin Nephrol 2019 Dec;92(6):302-311. doi: 10.5414/CN109842. PMID: 31587753
Ayasreh N, Bullich G, Miquel R, Furlano M, Ruiz P, Lorente L, Valero O, García-González MA, Arhda N, Garin I, Martínez V, Pérez-Gómez V, Fulladosa X, Arroyo D, Martínez-Vea A, Espinosa M, Ballarín J, Ars E, Torra R
Am J Kidney Dis 2018 Sep;72(3):411-418. Epub 2018 May 18 doi: 10.1053/j.ajkd.2018.03.019. PMID: 29784615
Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O; Kidney Disease: Improving Global Outcomes
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250

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