Skip to main content
SpringerLink
Log in

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood.

Methods

Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study.

Results

Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt.

Conclusions

Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Available.

Abbreviations

ALT:

Alanine aminotransferase

AP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

CKD:

Chronic kidney disease

CHF:

Congenital hepatic fibrosis

CLKT:

Combined liver-kidney transplantation

IRB:

Institutional review board

GGT:

γ-Glutamyltranspeptidase

eGFR:

Estimated glomerular filtration rate

M/F:

Male/female

IU:

International units

References

  1. Guay-Woodford LM, Bissler JJ, Braun MC, Bockenhauer D, Cadnapaphornchai MA, Dell KM, Kerecuk L, Liebau MC, Alonso-Peclet MH, Shneider B, Emre S, Heller T, Kamath BM, Murray KF, Moise K, Eichenwald EE, Evans J, Keller RL, Wilkins-Haug L, Bergmann C, Gunay-Aygun M, Hooper SR, Hardy KK, Hartung EA, Streisand R, Perrone R, Moxey-Mims M (2014) Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr 165:611–617

    Article  Google Scholar 

  2. Srinath A, Shneider BL (2012) Congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. J Pediatr Gastroenterol Nutr 54:580–587

    Article  Google Scholar 

  3. Blyth H, Ockenden BG (1971) Polycystic disease of kidney and liver presenting in childhood. J Med Genet 8:257–284

    Article  CAS  Google Scholar 

  4. Osathanondh V, Potter EL (1964) Pathogenesis of polycystic kidneys. Type 1 due to hyperplasia of interstitial portions of collecting tubules. Arch Pathol 77:466–473

    CAS  PubMed  Google Scholar 

  5. Davis ID, Ho M, Hupertz V, Avner ED (2003) Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease. Pediatr Transplant 7:364–369

    Article  Google Scholar 

  6. Khan K, Schwarzenberg SJ, Sharp HL, Matas AJ, Chavers BM (2002) Morbidity from congenital hepatic fibrosis after renal transplantation for autosomal recessive polycystic kidney disease. Am J Transplant 2:360–365

    Article  Google Scholar 

  7. Luoto TT, Pakarinen MP, Jahnukainen T, Jalanko H (2014) Liver disease in autosomal recessive polycystic kidney disease: clinical characteristics and management in relation to renal failure. J Pediatr Gastroenterol Nutr 59:190–196

    Article  CAS  Google Scholar 

  8. Quintero Bernabeu J, Juamperez J, Muñoz M, Rodriguez O, Vilalta R, Molino JA, Asensio M, Bilbao I, Ariceta G, Rodrigo C, Charco R (2018) Successful long-term outcome of pediatric liver-kidney transplantation: a single-center study. Pediatr Nephrol 33:351–358

    Article  Google Scholar 

  9. Rawat D, Kelly DA, Milford DV, Sharif K, Lloyd C, McKiernan PJ (2013) Phenotypic variation and long-term outcome in children with congenital hepatic fibrosis. J Pediatr Gastroenterol Nutr 57:161–166

    Article  Google Scholar 

  10. Zerres K, Rudnik-Schöneborn S, Deget F, Holtkamp U, Brodehl J, Geisert J, Schärer K (1996) Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender. Arbeitsgemeinschaft fur Padiatrische, Nephrologie. Acta Paediatr 85:437–445

    Article  CAS  Google Scholar 

  11. National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–S266

    Google Scholar 

  12. Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman M, Graf J, Bryant JC, Kleta R, Garcia A, Edwards H, Piwnica-Worms K, Adams D, Bernardini I, Fischer RE, Krasnewich D, Oden N, Ling A, Quezado Z, Zak C, Daryanani KT, Turkbey B, Choyke P, Guay-Woodford LM, Gahl WA (2010) 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 5:972–984

    Article  CAS  Google Scholar 

  13. Capisonda R, Phan V, Traubuci J, Daneman A, Balfe JW, Guay-Woodford LM (2003) Autosomal recessive polycystic kidney disease: outcomes from a single-center experience. Pediatr Nephrol 18:119–126

    Article  Google Scholar 

  14. Burgmaier K, Kilian S, Bammens B, Benzing T, Billing H, Büscher A, Galiano M, Grundmann F, Klaus G, Mekahli D, Michel-Calemard L, Milosevski-Lomic G, Ranchin B, Sauerstein K, Schaefer S, Shroff R, Sterenborg R, Verbeeck S, Weber LT, Wicher D, Wühl E, Dötsch J, Schaefer F, Liebau MC (2019) Clinical courses and complications of young adults with autosomal recessive polycystic kidney disease (ARPKD). Sci Rep 9:7919

    Article  Google Scholar 

  15. Bergmann C, Senderek J, Windelen E, Kupper F, Middeldorf I, Schneider F, Dornia C, Rudnik-Schöneborn S, Konrad M, Schmitt CP, Seeman T, Neuhaus TJ, Vester U, Kirfel J, Büttner R, Zerres K, APN (Arbeitsgemeinschaft für Pädiatrische Nephrologie) (2005) Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int 67:829–848

    Article  CAS  Google Scholar 

  16. Fan Y, Ye J, Qian L, Zhao R, Zhang N, Xue L, Qiao L, Jiang L (2019) Risk factors and outcomes of acute kidney injury in ventilated newborns. Ren Fail 41:995–1000

    Article  CAS  Google Scholar 

  17. Hartung EA, Guay-Woodford LM (2014) Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. Pediatrics 134:e833–e845

    Article  Google Scholar 

  18. Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gerstein M, Piwnica-Worms K, Choyke P, Daryanani KT, Turkbey B, Fischer R, Bernardini I, Sincan M, Zhao X, Sandler NG, Roque A, Douek DC, Graf J, Huizing M, Bryant JC, Mohan P, Gahl WA, Heller T (2013) Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology 144:112–121 e2

    Article  Google Scholar 

  19. El Mouzan MI, Abdullah AM, Al-Mofleh IA (2004) Yield of endoscopy in children with hematemesis. Trop Gastroenterol 25:44–46

    PubMed  Google Scholar 

  20. Grimaldi-Bensouda L, Abenhaim L, Michaud L, Mouterde O, Jonville-Béra AP, Giraudeau B, David B, Autret-Leca E (2010) Clinical features and risk factors for upper gastrointestinal bleeding in children: a case-crossover study. Eur J Clin Pharmacol 66:831–837

    Article  Google Scholar 

  21. Ling SC, Walters T, McKiernan PJ, Schwarz KB, Garcia-Tsao G, Shneider BL (2011) Primary prophylaxis of variceal hemorrhage in children with portal hypertension: a framework for future research. J Pediatr Gastroenterol Nutr 52:254–261

    Article  Google Scholar 

  22. van Heurn LW, Saing H, Tam PK (2004) Portoenterostomy for biliary atresia: long-term survival and prognosis after esophageal variceal bleeding. J Pediatr Surg 39:6–9

    Article  Google Scholar 

  23. Luoto T, Koivusalo A, Pakarinen M (2020) Long-term outcomes and health perceptions in pediatric-onset portal hypertension complicated by varices. J Pediatr Gastroenterol Nutr 70:628–634

    Article  Google Scholar 

  24. Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy VG, Poupon R (2004) Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology 40:652–659

    Article  Google Scholar 

  25. Mekahli D, van Stralen KJ, Bonthuis M, Jager KJ, Balat A, Benetti E, Godefroid N, Edvardsson VO, Heaf JG, Jankauskiene A, Kerecuk L, Marinova S, Puteo F, Seeman T, Zurowska A, Pirenne J, Schaefer F, Groothoff JW, ESPN/ERA-EDTA Registry (2016) Kidney versus combined kidney and liver transplantation in young people with autosomal recessive polycystic kidney disease: data from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry. Am J Kidney Dis 68:782–788

    Article  Google Scholar 

  26. Telega G, Cronin D, Avner ED (2013) New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications. Pediatr Transplant 17:328–335

    Article  Google Scholar 

Download references

Acknowledgments

We thank all physicians who contributed to data by filling in the patients’ medical records.

Code availability

Not applicable.

Funding

Nicolas Garcelon was partially financed by The French National Research Agency, under the C’IL-LICO project (17-RHUS-0002). The other authors received no external funding.

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, MARHEA Reference Center, Hôpital Universitaire Necker-Enfants Malades, AP-HP, 149 Rue de Sèvres, 75015, Paris, France

    Guillaume Dorval, Olivia Boyer, Laurence Heidet, Pauline Krug, Marina Charbit, Saoussen Krid, Nathalie Biebuyck & Rémi Salomon

  2. Imagine Institute, Université de Paris, Paris, France

    Guillaume Dorval, Olivia Boyer, Laurence Heidet, Pauline Krug, Marina Charbit, Saoussen Krid, Nathalie Biebuyck & Rémi Salomon

  3. Department of Pediatric Nephrology, Robert Debré Hospital, AP-HP, Paris, France

    Anne Couderc

  4. Department of Pediatric Nephrology, Armand Trousseau Hospital, AP-HP, Paris, France

    Jean-Daniel Delbet

  5. Department of Gastroenterology-Hepatology-Nutrition, Reference Center for Biliary Atresia and Cholestatic Genetic Diseases, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Paris, France

    Dominique Debray, Muriel Girard & Florence Lacaille

  6. Department of Pediatric Nephrology, Hôpital Universitaire Pellegrin, Bordeaux, France

    Brigitte Llanas

  7. Department of Pediatric Nephrology, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France

    Marc Fila

  8. Department of Nephrology and Transplantation, Centre Hospitalier Universitaire de Besançon, Besançon, France

    Cécile Courivaud

  9. Laboratory of Hereditary Kidney Diseases, Imagine Institute, INSERM U1163, Paris Descartes University, Paris, France

    Frances Tilley

  10. UMR 1163, Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, France

    Nicolas Garcelon

  11. Department of Pediatric Surgery, Necker-Enfants Malades Hospital, AP-HP, Paris, France

    Thomas Blanc & Christophe Chardot

Authors
  1. Guillaume Dorval
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivia Boyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne Couderc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean-Daniel Delbet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurence Heidet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dominique Debray
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pauline Krug
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Muriel Girard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Brigitte Llanas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marina Charbit
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Saoussen Krid
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nathalie Biebuyck
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marc Fila
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Cécile Courivaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Frances Tilley
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Nicolas Garcelon
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Thomas Blanc
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Christophe Chardot
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Rémi Salomon
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Florence Lacaille
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guillaume Dorval.

Ethics declarations

The local institutional review board (IRB) approved the study (Comité de Protection des Personnes, Ile de France II, n° ID-RCB).

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(PDF 45 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dorval, G., Boyer, O., Couderc, A. et al. Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease. Pediatr Nephrol 36, 1165–1173 (2021). https://doi.org/10.1007/s00467-020-04808-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-020-04808-9

Keywords

Search

Navigation