Download PDF
J Pediatr Genet 2021; 10(01): 001-008
DOI: 10.1055/s-0040-1714701
Review Article

Autosomal Recessive Polycystic Kidney Disease—The Clinical Aspects and Diagnostic Challenges

Dorota Wicher
1   Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland
,
Łukasz Obrycki
2   Department of Nephrology, Kidney Transplantation and Hypertension, Children's Memorial Health Institute, Warsaw, Poland
,
Irena Jankowska
3   Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Clinical features also include growth failure and neurocognitive impairment. Plurality of clinical aspects requires multidisciplinary approach to treatment and care of patients. Until recently, diagnosis was based on clinical criteria. Results of genetic testing show the molecular basis of polycystic kidneys disease is heterogeneous, and differential diagnosis is essential. The aim of the article is to discuss the role of genetic testing and its difficulties in diagnostics of ARPKD in children.

Keywords

autosomal recessive polycystic kidney disease - congenital hepatic fibrosis - next-generation sequencing


Publication History

Received: 06 May 2020

Accepted: 18 June 2020

Article published online:
29 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Veland IR, Awan A, Pedersen LB, Yoder BK, Christensen ST. Primary cilia and signaling pathways in mammalian development, health and disease. Nephron, Physiol 2009; 111 (03) 39-53
    CrossrefPubMedGoogle Scholar
  • 2 Masyuk AI, Masyuk TV, LaRusso NF. Cholangiocyte primary cilia in liver health and disease. Dev Dyn 2008; 237 (08) 2007-2012
    CrossrefPubMedGoogle Scholar
  • 3 Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 2011; 26 (07) 1039-1056
    CrossrefPubMedGoogle Scholar
  • 4 Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 2009; 151C (04) 296-306
    CrossrefPubMedGoogle Scholar
  • 5 Onuchic LF, Furu L, Nagasawa Y. et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. Am J Hum Genet 2002; 70 (05) 1305-1317
    CrossrefPubMedGoogle Scholar
  • 6 Ward CJ, Hogan MC, Rossetti S. et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet 2002; 30 (03) 259-269
    CrossrefPubMedGoogle Scholar
  • 7 Puder S, Fischer T, Mierke CT. The transmembrane protein fibrocystin/polyductin regulates cell mechanics and cell motility. Phys Biol 2019; 16 (06) 066006
    CrossrefPubMedGoogle Scholar
  • 8 Lu H, Galeano MCR, Ott E. et al. Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. Nat Genet 2017; 49 (07) 1025-1034
    CrossrefPubMedGoogle Scholar
  • 9 Hartung EA, Guay-Woodford LM. Polycystic kidney disease: DZIP1L defines a new functional zip code for autosomal recessive PKD. Nat Rev Nephrol 2017; 13 (09) 519-520
    CrossrefPubMedGoogle Scholar
  • 10 Bergmann C. ARPKD and early manifestations of ADPKD: the original polycystic kidney disease and phenocopies. Pediatr Nephrol 2015; 30 (01) 15-30
    CrossrefPubMedGoogle Scholar
  • 11 Szabó T, Orosz P, Balogh E. et al. Comprehensive genetic testing in children with a clinical diagnosis of ARPKD identifies phenocopies. Pediatr Nephrol 2018; 33 (10) 1713-1721
    CrossrefPubMedGoogle Scholar
  • 12 Hartung EA, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. Pediatrics 2014; 134 (03) e833-e845
    CrossrefPubMedGoogle Scholar
  • 13 Rivas A, Epelman M, Danzer E, Adzick NS, Victoria T. Prenatal MR imaging features of Caroli syndrome in association with autosomal recessive polycystic kidney disease. Radiol Case Rep 2018; 14 (02) 265-268
    CrossrefPubMedGoogle Scholar
  • 14 Roy S, Dillon MJ, Trompeter RS, Barratt TM. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol 1997; 11 (03) 302-306
    CrossrefPubMedGoogle Scholar
  • 15 Bergmann C. Genetics of autosomal recessive polycystic kidney disease and its differential diagnoses. Front Pediatr 2018; 5: 221
    Google Scholar
  • 16 Garel J, Lefebvre M, Cassart M. et al. Prenatal ultrasonography of autosomal dominant polycystic kidney disease mimicking recessive type: case series. Pediatr Radiol 2019; 49 (07) 906-912
    CrossrefPubMedGoogle Scholar
  • 17 Avni FE, Garel C, Cassart M, D'Haene N, Hall M, Riccabona M. Imaging and classification of congenital cystic renal diseases. AJR Am J Roentgenol 2012; 198 (05) 1004-1013
    CrossrefPubMedGoogle Scholar
  • 18 Burgmaier K, Kunzmann K, Ariceta G. et al; ESCAPE Study Group; GPN Study Group; ARegPKD consortium. Risk factors for early dialysis dependency in autosomal recessive polycystic kidney disease. J Pediatr 2018; 199: 22-28.e6
    CrossrefPubMedGoogle Scholar
  • 19 Gimpel C, Avni EF, Breysem L. et al. Imaging of kidney cysts and cystic kidney diseases in children: an international working group consensus statement. Radiology 2019; 290 (03) 769-782
    CrossrefPubMedGoogle Scholar
  • 20 Iorio P, Heidet L, Rutten C. et al. The “salt and pepper” pattern on renal ultrasound in a group of children with molecular-proven diagnosis of ciliopathy-related renal diseases. Pediatr Nephrol 2020; 35 (06) 1033-1040
    CrossrefPubMedGoogle Scholar
  • 21 Büscher R, Büscher AK, Weber S. et al. Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes. Pediatr Nephrol 2014; 29 (10) 1915-1925
    CrossrefPubMedGoogle Scholar
  • 22 Goto M, Hoxha N, Osman R, Dell KM. The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease. Pediatr Nephrol 2010; 25 (12) 2449-2457
    CrossrefPubMedGoogle Scholar
  • 23 Dias NF, Lanzarini V, Onuchic LF, Koch VHK. Clinical aspects of autosomal recessive polycystic kidney disease. J Bras Nefrol 2010; 32 (03) 263-267
    CrossrefPubMedGoogle Scholar
  • 24 Herman TE, Siegel MJ. Pyramidal hyperechogenicity in autosomal recessive polycystic kidney disease resembling medullary nephrocalcinosis. Pediatr Radiol 1991; 21 (04) 270-271
    CrossrefPubMedGoogle Scholar
  • 25 Warady BA, Alexander SR, Watkins S, Kohaut E, Harmon WE. Optimal care of the pediatric end-stage renal disease patient on dialysis. Am J Kidney Dis 1999; 33 (03) 567-583
    CrossrefPubMedGoogle Scholar
  • 26 Sweeney Jr WE, Avner ED. Diagnosis and management of childhood polycystic kidney disease. Pediatr Nephrol 2011; 26 (05) 675-692
    CrossrefPubMedGoogle Scholar
  • 27 Sweeney WE, Avner ED. Polycystic Kidney Disease, Autosomal Recessive. GeneReviews® [Internet], July 19, 2001. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1326/ . Last Revision: February 14, 2019
  • 28 Telega G, Cronin D, Avner E. New approaches to the ARPKD patient with dual kidney – liver complications. Pediatr Transplant 2013; 17 (04) 328-335
    CrossrefPubMedGoogle Scholar
  • 29 Karava V, Benzouid C, Hogan J, Dossier C, Denjean AP, Deschênes G. Early cardiovascular manifestations in children and adolescents with autosomal dominant polycystic kidney disease: a single center study. Pediatr Nephrol 2018; 33 (09) 1513-1521
    CrossrefPubMedGoogle Scholar
  • 30 Chalhoub V, Abi-Rafeh L, Hachem K, Ayoub E, Yazbeck P. Intracranial aneurysm and recessive polycystic kidney disease: the third reported case. JAMA Neurol 2013; 70 (01) 114-116
    CrossrefPubMedGoogle Scholar
  • 31 Elchediak DS, Cahill AM, Furth EE, Kaplan BS, Hartung EA. Extracranial aneurysms in 2 patients with autosomal recessive polycystic kidney disease. Case Rep Nephrol Dial 2017; 7 (02) 34-42
    CrossrefPubMedGoogle Scholar
  • 32 Helal I, Handous I, Khadhar M, Bezzine H, Hamida FB, Abdallah TB. Ruptured intracranial aneurysm and recessive polycystic kidney disease: a rare association. Saudi J Kidney Dis Transpl 2019; 30 (04) 982-984
    CrossrefPubMedGoogle Scholar
  • 33 Burgmaier K, Brandt J, Shroff R. et al. Gastrostomy tube insertion in pediatric patients with autosomal recessive polycystic kidney disease (ARPKD): current practice. Front Pediatr 2018; 6: 164
    CrossrefPubMedGoogle Scholar
  • 34 Hartung EA, Dell KM, Matheson M, Warady BA, Furth SL. Growth in children with autosomal recessive polycystic kidney disease in the CKiD cohort study. Front Pediatr 2016; 4: 82
    CrossrefPubMedGoogle Scholar
  • 35 Hooper SR. Risk factors for neurocognitive functioning in children with autosomal recessive polycystic kidney disease. Front Pediatr 2017; 5: 107
    CrossrefPubMedGoogle Scholar
  • 36 Adeva M, El-Youssef M, Rossetti S. et al. Clinical and molecular characterization defines a broadened spectrum of autosomal recessive polycystic kidney disease (ARPKD). Medicine (Baltimore) 2006; 85 (01) 1-21
    CrossrefPubMedGoogle Scholar
  • 37 Melchionda S, Palladino T, Castellana S. et al. Expanding the mutation spectrum in 130 probands with ARPKD: identification of 62 novel PKHD1 mutations by sanger sequencing and MLPA analysis. J Hum Genet 2016; 61 (09) 811-821
    CrossrefPubMedGoogle Scholar
  • 38 Bergmann C, Senderek J, Windelen E. et al; APN (Arbeitsgemeinschaft für Pädiatrische Nephrologie). Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int 2005; 67 (03) 829-848
    CrossrefPubMedGoogle Scholar
  • 39 Rossetti S, Harris PC. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol 2007; 18 (05) 1374-1380
    CrossrefPubMedGoogle Scholar
  • 40 Gigarel N, Frydman N, Burlet P. et al. Preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease. Reprod Biomed Online 2008; 16 (01) 152-158
    CrossrefPubMedGoogle Scholar
  • 41 International Society for Prenatal Diagnosis; Society for Maternal and Fetal Medicine; Perinatal Quality Foundation. the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn 2018; 38 (01) 6-9
    CrossrefPubMedGoogle Scholar
  • 42 Armstrong ME, Thomas CP. Diagnosis of monogenic chronic kidney diseases. Curr Opin Nephrol Hypertens 2019; 28 (02) 183-194
    CrossrefPubMedGoogle Scholar
  • 43 Roume J, Ville Y. Prenatal diagnosis of genetic renal diseases: breaking the code. Ultrasound Obstet Gynecol 2004; 24 (01) 10-18
    CrossrefPubMedGoogle Scholar
  • 44 Cabezas OR, Flanagan SE, Stanescu H. et al. Polycystic kidney disease with hyperinsulinemic hypoglycemia caused by a promoter mutation in phosphomannomutase 2. J Am Soc Nephrol 2017; 28 (08) 2529-2539
    CrossrefPubMedGoogle Scholar
  • 45 Shukla AR, Kiddoo DA, Canning DA. Unilateral nephrectomy as palliative therapy in an infant with autosomal recessive polycystic kidney disease. J Urol 2004; 172 (5 Pt 1): 2000-2001
    CrossrefPubMedGoogle Scholar
  • 46 Sweeney Jr W, Gunay-Aygun M, Patil A, Avner ED. Childhood polycystic kidney disease. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Francesco E, Goldstein S. eds. Pediatric Nephrology, 7th ed. Heidelberg, Berlin: Springer; 2016: 1103-1153
    Google Scholar
  • 47 Chapman AB, Gabow PA. Hypertension in autosomal dominant polycystic kidney disease. Kidney Int Suppl 1997; 61: S71-S73
    PubMedGoogle Scholar
  • 48 Janssens P, Weydert C, De Rechter S, Wissing KM, Liebau MC, Mekahli D. Expanding the role of vasopressin antagonism in polycystic kidney diseases: from adults to children?. Pediatr Nephrol 2018; 33 (03) 395-408
    CrossrefPubMedGoogle Scholar
  • 49 Shneider BL, Bosch J, de Franchis R. et al; expert panel of the Children's Hospital of Pittsburgh of UPMC. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. Pediatr Transplant 2012; 16 (05) 426-437
    CrossrefPubMedGoogle Scholar
  • 50 Pimenta JR, Ferreira AR, Bittencourt PFS, Resende CB, Fagundes EDT, Silva IM. Evaluation of primary prophylaxis with propranolol and elastic band ligation in variceal bleeding in cirrhotic children and adolescents. Arq Gastroenterol 2016; 53 (04) 257-261
    CrossrefPubMedGoogle Scholar
  • 51 Ahuja C, Farsad K, Chadha M. An overview of splenic embolization. AJR Am J Roentgenol 2015; 205 (04) 720-725
    CrossrefPubMedGoogle Scholar
  • 52 Telega G, Cronin D, Avner ED. New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications. Pediatr Transplant 2013; 17 (04) 328-335
    CrossrefPubMedGoogle Scholar
  • 53 Yoshida T, Hiratsuka K, Yamashita M, Matsui A, Hayashi M. Posterior reversible encephalopathy syndrome in a uremic patient with autosomal recessive polycystic kidney disease. CEN Case Rep 2015; 4 (02) 238-242
    CrossrefPubMedGoogle Scholar
  • 54 Bergmann C. Early and severe polycystic kidney disease and related ciliopathies: an emerging field of interest. Nephron 2019; 141 (01) 50-60
    CrossrefPubMedGoogle Scholar
  • 55 Lilova M, Kaplan BS, Meyers KEC. Recombinant human growth hormone therapy in autosomal recessive polycystic kidney disease. Pediatr Nephrol 2003; 18 (01) 57-61
    CrossrefPubMedGoogle Scholar
  • 56 Jahnukainen T, Kirjavainen T, Luoto T. et al. Long-term pulmonary function in children with recessive polycystic kidney disease. Arch Dis Child 2015; 100 (10) 944-947
    CrossrefPubMedGoogle Scholar
  • 57 Gunay-Aygun M, Font-Montgomery E, Lukose L. et al. Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol 2010; 5 (06) 972-984
    CrossrefPubMedGoogle Scholar
  • 58 Wen J. Congenital hepatic fibrosis in autosomal recessive polycystic kidney disease. Clin Transl Sci 2011; 4 (06) 460-465
    CrossrefPubMedGoogle Scholar
  • 59 Sweeney WE, Frost P, Avner ED. Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease. World J Nephrol 2017; 6 (04) 188-200
    CrossrefPubMedGoogle Scholar
  • 60 Zerres K, Rudnik-Schöneborn S, Deget F. et al. Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender. Arbeitsgemeinschaft für Pädiatrische, Nephrologie. Acta Paediatr 1996; 85 (04) 437-445
    CrossrefPubMedGoogle Scholar