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Congenital anomalies of kidney and urinary tract 1(RHDNS1; CAKUT1)

MedGen UID:
322763
Concept ID:
C1835826
Congenital Abnormality
Synonyms: Congenital anomalies of kidney and urinary tract 1, susceptibility to; Renal hypodysplasia, nonsyndromic, 1
 
Gene (location): DSTYK (1q32.1)
 
Monarch Initiative: MONDO:0012561
OMIM®: 610805

Definition

Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a broad spectrum of renal and urinary tract malformations. CAKUT structural anomalies range from complete renal agenesis (the most severe), to renal hypodysplasia, multicystic kidney dysplasia, duplex renal collecting system, ureteropelvic junction obstruction (UPJO), megaureter, posterior urethral valves (PUV), and vesicoureteral reflux (VUR). Renal abnormalities are observed in close relatives of up to 10% of CAKUT patients, although these are frequently asymptomatic. The phenotype often does not follow classic mendelian inheritance: family members with the same genetic defect may have variable phenotypes, ranging from severe renal insufficiency to asymptomatic anomalies. CAKUT occurs in about 1 in 500 live births, but are severe enough to cause neonatal death in about 1 in 2,000 births. In addition, CAKUT can occur in syndromic disorders in association with other congenital anomalies, such as papillorenal syndrome (120330) (summary by Renkema et al., 2011). Genetic Heterogeneity of Congenital Anomalies of Kidney and Urinary Tract Also see CAKUT2 (143400), caused by mutation in the TBX18 gene (604613) on chromosome 6q14, and CAKUT3 (618270), caused by mutation in the NRIP1 gene (602490) on chromosome 21q. [from OMIM]

Clinical features

From HPO
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Unilateral renal agenesis
MedGen UID:
75607
Concept ID:
C0266294
Congenital Abnormality
A unilateral form of agenesis of the kidney.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Ureteropelvic junction obstruction
MedGen UID:
105482
Concept ID:
C0521619
Anatomical Abnormality
Blockage of urine flow from the renal pelvis to the proximal ureter.
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.

Professional guidelines

PubMed

Mosca M, Bacchetta J, Chamouard V, Rascle P, Dubois V, Paul S, Mekki Y, Picard C, Bertholet-Thomas A, Ranchin B, Sellier-Leclerc AL
Arch Pediatr 2023 Apr;30(3):165-171. Epub 2023 Mar 10 doi: 10.1016/j.arcped.2023.01.005. PMID: 36907728
de Pádua Paz I, Konstantyner T, de Castro Cintra Sesso R, de Xavier Pinto CC, de Camargo MFC, Nogueira PCK
Pediatr Nephrol 2021 Sep;36(9):2827-2835. Epub 2021 Mar 6 doi: 10.1007/s00467-021-05009-8. PMID: 33675411
Montini G, Busutti M, Yalcinkaya F, Woolf AS, Weber S; European Society for Paediatric Nephrology Working Group on Congenital Anomalies of the Kidney and Urinary Tract
J Nephrol 2018 Feb;31(1):95-102. Epub 2017 Jun 24 doi: 10.1007/s40620-017-0417-7. PMID: 28647851Free PMC Article

Recent clinical studies

Etiology

Mattoo TK, Mohammad D
Pediatr Clin North Am 2022 Dec;69(6):1115-1129. Epub 2022 Oct 29 doi: 10.1016/j.pcl.2022.07.007. PMID: 36880925
Harada R, Hamasaki Y, Okuda Y, Hamada R, Ishikura K
Pediatr Nephrol 2022 Jun;37(6):1215-1229. Epub 2021 Jun 6 doi: 10.1007/s00467-021-05145-1. PMID: 34091754
Rao J, Liu X, Mao J, Tang X, Shen Q, Li G, Sun L, Bi Y, Wang X, Qian Y, Wu B, Wang H, Zhou W, Ma D, Zheng B, Shen Y, Chen Z, Luan J, Wang X, Wang M, Dang X, Wang Y, Wu Y, Hou L, Sun S, Li Q, Liu X, Bai H, Yang Y, Shao X, Li Y, Zheng S, Han M, Liu C, Cao G, Zhao L, Qiu S, Dong Y, Zhu Y, Wang F, Zhang D, Li Y, Zhao L, Yang C, Luo X, Chen L, Jiang X, Zhang A, Xu H; for “Internet Plus” Nephrology Alliance of National Center for Children's Care
Clin Genet 2019 Nov;96(5):402-410. Epub 2019 Jul 25 doi: 10.1111/cge.13606. PMID: 31328266
van der Ven AT, Connaughton DM, Ityel H, Mann N, Nakayama M, Chen J, Vivante A, Hwang DY, Schulz J, Braun DA, Schmidt JM, Schapiro D, Schneider R, Warejko JK, Daga A, Majmundar AJ, Tan W, Jobst-Schwan T, Hermle T, Widmeier E, Ashraf S, Amar A, Hoogstraaten CA, Hugo H, Kitzler TM, Kause F, Kolvenbach CM, Dai R, Spaneas L, Amann K, Stein DR, Baum MA, Somers MJG, Rodig NM, Ferguson MA, Traum AZ, Daouk GH, Bogdanović R, Stajić N, Soliman NA, Kari JA, El Desoky S, Fathy HM, Milosevic D, Al-Saffar M, Awad HS, Eid LA, Selvin A, Senguttuvan P, Sanna-Cherchi S, Rehm HL, MacArthur DG, Lek M, Laricchia KM, Wilson MW, Mane SM, Lifton RP, Lee RS, Bauer SB, Lu W, Reutter HM, Tasic V, Shril S, Hildebrandt F
J Am Soc Nephrol 2018 Sep;29(9):2348-2361. Epub 2018 Aug 24 doi: 10.1681/ASN.2017121265. PMID: 30143558Free PMC Article
Winyard P, Chitty LS
Semin Fetal Neonatal Med 2008 Jun;13(3):142-51. Epub 2007 Dec 11 doi: 10.1016/j.siny.2007.10.009. PMID: 18065301

Diagnosis

Mattoo TK, Mohammad D
Pediatr Clin North Am 2022 Dec;69(6):1115-1129. Epub 2022 Oct 29 doi: 10.1016/j.pcl.2022.07.007. PMID: 36880925
Rao J, Liu X, Mao J, Tang X, Shen Q, Li G, Sun L, Bi Y, Wang X, Qian Y, Wu B, Wang H, Zhou W, Ma D, Zheng B, Shen Y, Chen Z, Luan J, Wang X, Wang M, Dang X, Wang Y, Wu Y, Hou L, Sun S, Li Q, Liu X, Bai H, Yang Y, Shao X, Li Y, Zheng S, Han M, Liu C, Cao G, Zhao L, Qiu S, Dong Y, Zhu Y, Wang F, Zhang D, Li Y, Zhao L, Yang C, Luo X, Chen L, Jiang X, Zhang A, Xu H; for “Internet Plus” Nephrology Alliance of National Center for Children's Care
Clin Genet 2019 Nov;96(5):402-410. Epub 2019 Jul 25 doi: 10.1111/cge.13606. PMID: 31328266
van der Ven AT, Connaughton DM, Ityel H, Mann N, Nakayama M, Chen J, Vivante A, Hwang DY, Schulz J, Braun DA, Schmidt JM, Schapiro D, Schneider R, Warejko JK, Daga A, Majmundar AJ, Tan W, Jobst-Schwan T, Hermle T, Widmeier E, Ashraf S, Amar A, Hoogstraaten CA, Hugo H, Kitzler TM, Kause F, Kolvenbach CM, Dai R, Spaneas L, Amann K, Stein DR, Baum MA, Somers MJG, Rodig NM, Ferguson MA, Traum AZ, Daouk GH, Bogdanović R, Stajić N, Soliman NA, Kari JA, El Desoky S, Fathy HM, Milosevic D, Al-Saffar M, Awad HS, Eid LA, Selvin A, Senguttuvan P, Sanna-Cherchi S, Rehm HL, MacArthur DG, Lek M, Laricchia KM, Wilson MW, Mane SM, Lifton RP, Lee RS, Bauer SB, Lu W, Reutter HM, Tasic V, Shril S, Hildebrandt F
J Am Soc Nephrol 2018 Sep;29(9):2348-2361. Epub 2018 Aug 24 doi: 10.1681/ASN.2017121265. PMID: 30143558Free PMC Article
Sanna-Cherchi S, Westland R, Ghiggeri GM, Gharavi AG
J Clin Invest 2018 Jan 2;128(1):4-15. doi: 10.1172/JCI95300. PMID: 29293093Free PMC Article
Winyard P, Chitty LS
Semin Fetal Neonatal Med 2008 Jun;13(3):142-51. Epub 2007 Dec 11 doi: 10.1016/j.siny.2007.10.009. PMID: 18065301

Therapy

Evgenia G, Yafa F, Hadas A, Shelly L, Amit D, Landau D, Orly H
J Nephrol 2023 Jul;36(6):1571-1580. Epub 2023 Jun 21 doi: 10.1007/s40620-023-01668-y. PMID: 37341967
Mosca M, Bacchetta J, Chamouard V, Rascle P, Dubois V, Paul S, Mekki Y, Picard C, Bertholet-Thomas A, Ranchin B, Sellier-Leclerc AL
Arch Pediatr 2023 Apr;30(3):165-171. Epub 2023 Mar 10 doi: 10.1016/j.arcped.2023.01.005. PMID: 36907728
Stavas J, Diaz-Gonzalez de Ferris M, Johns A, Jain D, Bertram T
Blood Purif 2021;50(4-5):678-683. Epub 2021 Mar 1 doi: 10.1159/000512586. PMID: 33647913
Gulleroglu K, Baskin E, Kirnap M, Uslu N, Moray G, Haberal M
Exp Clin Transplant 2020 Jan;18(Suppl 1):41-43. doi: 10.6002/ect.TOND-TDTD2019.O21. PMID: 32008492
Postoev VA, Grjibovski AM, Kovalenko AA, Anda EE, Nieboer E, Odland JØ
Birth Defects Res A Clin Mol Teratol 2016 Mar;106(3):185-93. Epub 2016 Feb 2 doi: 10.1002/bdra.23475. PMID: 26833755

Prognosis

Westland R, Renkema KY, Knoers NVAM
Clin J Am Soc Nephrol 2020 Dec 31;16(1):128-137. Epub 2020 Apr 20 doi: 10.2215/CJN.14661119. PMID: 32312792Free PMC Article
van der Ven AT, Connaughton DM, Ityel H, Mann N, Nakayama M, Chen J, Vivante A, Hwang DY, Schulz J, Braun DA, Schmidt JM, Schapiro D, Schneider R, Warejko JK, Daga A, Majmundar AJ, Tan W, Jobst-Schwan T, Hermle T, Widmeier E, Ashraf S, Amar A, Hoogstraaten CA, Hugo H, Kitzler TM, Kause F, Kolvenbach CM, Dai R, Spaneas L, Amann K, Stein DR, Baum MA, Somers MJG, Rodig NM, Ferguson MA, Traum AZ, Daouk GH, Bogdanović R, Stajić N, Soliman NA, Kari JA, El Desoky S, Fathy HM, Milosevic D, Al-Saffar M, Awad HS, Eid LA, Selvin A, Senguttuvan P, Sanna-Cherchi S, Rehm HL, MacArthur DG, Lek M, Laricchia KM, Wilson MW, Mane SM, Lifton RP, Lee RS, Bauer SB, Lu W, Reutter HM, Tasic V, Shril S, Hildebrandt F
J Am Soc Nephrol 2018 Sep;29(9):2348-2361. Epub 2018 Aug 24 doi: 10.1681/ASN.2017121265. PMID: 30143558Free PMC Article
Ristoska-Bojkovska N
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2017 Mar 1;38(1):59-62. doi: 10.1515/prilozi-2017-0008. PMID: 28593883
Ingelfinger JR, Kalantar-Zadeh K, Schaefer F; World Kidney Day Steering Committee
Semin Nephrol 2016 Jan;36(1):1-6. doi: 10.1016/j.semnephrol.2016.01.010. PMID: 27085729
Winyard P, Chitty LS
Semin Fetal Neonatal Med 2008 Jun;13(3):142-51. Epub 2007 Dec 11 doi: 10.1016/j.siny.2007.10.009. PMID: 18065301

Clinical prediction guides

Du X, Wang C, Liu J, Yu M, Ju H, Xue S, Li Y, Liu J, Dai R, Chen J, Zhai Y, Rao J, Wang X, Sun Y, Sun L, Wu X, Xu H, Shen Q
Hum Genomics 2024 Apr 24;18(1):41. doi: 10.1186/s40246-024-00606-8. PMID: 38654324Free PMC Article
Matsell DG, Catapang M, Becknell B
Pediatr Nephrol 2023 Oct;38(10):3407-3415. Epub 2023 May 3 doi: 10.1007/s00467-023-05992-0. PMID: 37133803Free PMC Article
Woolf AS
Pediatr Nephrol 2022 Nov;37(11):2785-2791. Epub 2022 May 16 doi: 10.1007/s00467-022-05576-4. PMID: 35575937Free PMC Article
Okuda Y, Soohoo M, Ishikura K, Tang Y, Obi Y, Laster M, Rhee CM, Streja E, Kalantar-Zadeh K
Pediatr Nephrol 2020 May;35(5):851-860. Epub 2020 Feb 4 doi: 10.1007/s00467-019-04457-7. PMID: 32020338Free PMC Article
Winyard P, Chitty LS
Semin Fetal Neonatal Med 2008 Jun;13(3):142-51. Epub 2007 Dec 11 doi: 10.1016/j.siny.2007.10.009. PMID: 18065301

Recent systematic reviews

Jadresić L, Au H, Woodhouse C, Nitsch D
Pediatr Nephrol 2021 Jan;36(1):119-132. Epub 2020 Jun 28 doi: 10.1007/s00467-020-04679-0. PMID: 32596798
Shahdadi H, Sheyback M, Rafiemanesh H, Balouchi A, Bouya S, Mahmoudirad G
Ann Glob Health 2019 Mar 13;85(1) doi: 10.5334/aogh.2391. PMID: 30873815Free PMC Article
Hofmann AD, Duess JW, Puri P
Pediatr Surg Int 2014 Aug;30(8):757-61. Epub 2014 Jun 29 doi: 10.1007/s00383-014-3529-3. PMID: 24974188
Westland R, Schreuder MF, Ket JC, van Wijk JA
Nephrol Dial Transplant 2013 Jul;28(7):1844-55. Epub 2013 Feb 28 doi: 10.1093/ndt/gft012. PMID: 23449343

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