Skip to main content
SpringerLink
Log in

Severe parental phenotype associates with hypertension in children with ADPKD

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

Abstract

Background

Early detection of hypertension in children with autosomal polycystic kidney disease (ADPKD) may be beneficial, but screening children at risk of ADPKD remains controversial. We investigated determinants of hypertension in children with ADPKD to help identify a subgroup of children at risk of ADPKD for whom screening for the disease and/or its complications would be more relevant.

Methods

In a retrospective study including consecutive children with ADPKD aged 5–18 years and followed at Saint-Luc Hospital Brussels between 2006 and 2020, we investigated the potential association between genotype, clinical characteristics and parental phenotype, and presence of hypertension. Hypertension was defined as blood pressure > P95 during 24-h ambulatory monitoring or anti-hypertensive therapy use. Parental phenotype was considered severe based on age at kidney failure, Mayo Clinic Imaging Classification and rate of eGFR decline.

Results

The study enrolled 55 children with ADPKD (mean age 9.9 ± 2.2 years, 45% male), including 44 with a PKD1 mutation and 5 with no mutation identified. Nine (16%) children had hypertension. Hypertension in children was associated with parental phenotype severity (8/27 (30%) children with severe parental phenotype vs. 1/23 (4%) children with non-severe parental phenotype (p = 0.03)) and height-adjusted bilateral nephromegaly (6/9 (67%) children with bilateral nephromegaly vs. 3/44 (7%) children without bilateral nephromegaly (p < 0.001)).

Conclusions

Severe parental phenotype is associated with higher prevalence of hypertension in children with ADPKD. Hence, children of parents with severe ADPKD phenotype may be those who will most benefit from screening of the disease and/or yearly BP measures.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

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

Similar content being viewed by others

References

  1. Torres VE, Harris PC, Pirson Y (2007) Autosomal dominant polycystic kidney disease. Lancet 369:1287–1301. https://doi.org/10.1016/S0140-6736(07)60601-1

    Article  PubMed  Google Scholar 

  2. Chebib FT, Torres VE (2016) Autosomal dominant polycystic kidney disease: Core Curriculum 2016. Am J Kidney Dis 67:792–810. https://doi.org/10.1053/j.ajkd.2015.07.037

    Article  PubMed  Google Scholar 

  3. Cornec-Le Gall E, Torres VE, Harris PC (2018) Genetic complexity of autosomal dominant polycystic kidney and liver diseases. J Am Soc Nephrol 29:13–23. https://doi.org/10.1681/ASN.2017050483

    Article  PubMed  Google Scholar 

  4. Cornec-Le Gall E, Alam A, Perrone RD (2019) Autosomal dominant polycystic kidney disease. Lancet 393:919–935. https://doi.org/10.1016/S0140-6736(18)32782-X

    Article  PubMed  Google Scholar 

  5. Besse W, Chang AR, Luo JZ, Triffo WJ et al (2019) ALG9 mutation carriers develop kidney and liver cysts. J Am Soc Nephrol 30:2091–2102. https://doi.org/10.1681/ASN.2019030298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Senum SR, Li YSM, Benson KA, Joli G et al (2022) Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype. Am J Hum Genet 109:136–156. https://doi.org/10.1016/j.ajhg.2021.11.016

    Article  CAS  PubMed  Google Scholar 

  7. Cornec-Le Gall E, Audrézet MP, Chen JM, Hourmant M et al (2013) Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol 24:1006–1013. https://doi.org/10.1681/ASN.2012070650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ho TA, Godefroid N, Gruzon D, Haymann JP et al (2012) Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation. Kidney Int 82:1121–1129. https://doi.org/10.1038/ki.2012.225

    Article  CAS  PubMed  Google Scholar 

  9. Selistre L, de Souza V, Ranchin B, Hadj-Aissa A, Cochat P, Dubourg L (2012) Early renal abnormalities in children with postnatally diagnosed autosomal dominant polycystic kidney disease. Pediatr Nephrol 27:1589–1593. https://doi.org/10.1007/s00467-012-2192-y

    Article  PubMed  Google Scholar 

  10. Cadnapaphornchai MA (2015) Autosomal dominant polycystic kidney disease in children. Curr Opin Pediatr 27:193–200. https://doi.org/10.1097/MOP.0000000000000195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marlais M, Cuthell O, Langan D, Dudley J, Sinha MD, Winyard PJ (2016) Hypertension in autosomal dominant polycystic kidney disease: a meta-analysis. Arch Dis Child 101:1142–1147. https://doi.org/10.1136/archdischild-2015-310221

    Article  PubMed  Google Scholar 

  12. Reddy BV, Chapman AB (2017) The spectrum of autosomal dominant polycystic kidney disease in children and adolescents. Pediatr Nephrol 32:31–42. https://doi.org/10.1007/s00467-016-3364-y

    Article  PubMed  Google Scholar 

  13. Gimpel C, Bergmann C, Mekahli D (2021) The wind of change in the management of autosomal dominant polycystic kidney disease in childhood. Pediatr Nephrol 37:473–487. https://doi.org/10.1007/s00467-021-04974-4

    Article  PubMed  PubMed Central  Google Scholar 

  14. Massella L, Mekahli D, Paripović D, Prikhodina L et al (2018) Prevalence of hypertension in children with early-stage ADPKD. Clin J Am Soc Nephrol 13:874–883. https://doi.org/10.2215/CJN.11401017

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marlais M, Rajalingam S, Gu H, Savis A, Sinha MD, Winyard PJ (2019) Central blood pressure and measures of early vascular disease in children with ADPKD. Pediatr Nephrol 34:1791–1797. https://doi.org/10.1007/s00467-019-04287-7

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA (2001) Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 59:1654–1662. https://doi.org/10.1046/j.1523-1755.2001.0590051654

    Article  CAS  PubMed  Google Scholar 

  17. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2008) Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int 74:1192–1196. https://doi.org/10.1038/ki.2008.397

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2009) Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol 4:820–829. https://doi.org/10.2215/CJN.02810608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cadnapaphornchai MA, Masoumi A, Strain JD, McFann K, Schrier RW (2011) Magnetic resonance imaging of kidney and cyst volume in children with ADPKD. Clin J Am Soc Nephrol 6:369–376. https://doi.org/10.2215/CJN.03780410

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chapman AB, Guay-Woodford LM (2009) Renal volume in children with ADPKD: size matters. Clin J Am Soc Nephrol 4:698–699. https://doi.org/10.2215/CJN.01410209

    Article  PubMed  Google Scholar 

  21. Gimpel C, Bergmann C, Bockenhauer D, Breysem L et al (2019) International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people. Nat Rev Nephrol 15:713–726. https://doi.org/10.1038/s41581-019-0155-2

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT et al (2015) Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 88:17–27. https://doi.org/10.1038/ki.2015.59

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lurbe E, Agabiti-Rosei E, Cruickshank JK, Dominiczak A et al (2016) European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens 34:1887–1920. https://doi.org/10.1097/HJH.0000000000001039

    Article  CAS  PubMed  Google Scholar 

  24. Gao A, Cachat F, Faouzi M, Bardy D, Mosig D, Meyrat BJ, Girardin E, Chehade H (2013) Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula. Kidney Int 83:524–530. https://doi.org/10.1038/ki.2012.388

    Article  CAS  PubMed  Google Scholar 

  25. Obrycki L, Sarnecki J, Lichosik M, Sopińska M et al (2022) Kidney length normative values in children aged 0–19 years – a multicenter study. Pediatr Nephrol 37:1075–1085. https://doi.org/10.1007/s00467-021-05303-5

    Article  PubMed  Google Scholar 

  26. Richards S, Aziz N, Bale S, Bick D et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30

    Article  PubMed  PubMed Central  Google Scholar 

  27. Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL et al (2015) Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol 26:160–172. https://doi.org/10.1681/ASN.2013101138

    Article  CAS  PubMed  Google Scholar 

  28. Lanktree MB, Guiard E, Li W, Akbari P et al (2019) Intrafamilial variability of ADPKD. Kidney Int Rep 4:995–1003. https://doi.org/10.1016/j.ekir.2019.04.018

    Article  PubMed  PubMed Central  Google Scholar 

  29. Barua M, Cil O, Paterson AD, Wang K, He N, Dicks E, Parfrey P, Pei Y (2009) Family history of renal disease severity predicts the mutated gene in ADPKD. J Am Soc Nephrol 20:1833–1838. https://doi.org/10.1681/ASN.2009020162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schrier RW, Brosnahan G, Cadnapaphornchai MA, Chonchol M, Friend K, Gitomer B, Rossetti S (2014) Predictors of autosomal polycystic kidney disease progression. J Am Soc Nephrol 25:2399–2418. https://doi.org/10.1681/ASN.2013111184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K, Rudan I (2019) Global prevalence of hypertension in children: a systematic review and meta-analysis. JAMA Pediatr 173:1154–1163. https://doi.org/10.1001/jamapediatrics.2019.3310

    Article  PubMed  PubMed Central  Google Scholar 

  32. De Rechter S, Bammens B, Schaefer F, Liebau MC, Mekahli D (2018) Unmet needs and challenges for follow-up and treatment of autosomal dominant polycystic kidney disease: the paediatric perspective. Clin Kidney J 11(Suppl 1):i14–i26. https://doi.org/10.1093/ckj/sfy088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Breysem L, De Rechter S, De Keyzer F, Smet MH et al (2018) 3DUS as an alternative to MRI for measuring renal volume in children with autosomal dominant polycystic kidney disease. Pediatr Nephrol 33:827–835. https://doi.org/10.1007/s00467-017-3862-6

    Article  PubMed  Google Scholar 

  34. Heyer CM, Sundsbak JL, Abebe KZ, Chapman AB et al (2016) Predicted mutation strength of nontruncating PKD1 mutations aids genotype-phenotype correlations in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 27:2872–2884. https://doi.org/10.1681/ASN.2015050583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Levin A, Stevens PE, Bilous RW, Coresh J et al (2013) KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150. https://doi.org/10.1038/kisup.2012.73

    Article  Google Scholar 

  36. Pottel H, Björk J, Delanaye P, Nyman U (2022) Evaluation of the creatinine-based chronic kidney disease in children (under 25 years) equation in healthy children and adolescents. Pediatr Nephrol 37:2213–2216. https://doi.org/10.1007/s00467-022-05429-0

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank O. Devuyst and Y. Pirson for their constructive advice and review of the manuscript, as well as P. Harris and SR Senum for their help in the categorization of the PKD1 variants.

Six of the authors of this publication are members of the European Reference Network for Rare Kidney Diseases (ERKNet).

Funding

This study was supported by a private grant (“Prix Marlène et Philippe Cloës”), and an unrestricted educational grant from Otsuka Pharmaceuticals (Nathalie Demoulin).

Author information

Author notes

  1. Nathalie Demoulin and Elliott Van Regemorter contributed equally

Authors and Affiliations

  1. Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Nathalie Demoulin, Elliott Van Regemorter, Johann Morelle & Valentine Gillion

  2. Institut de Recherche Expérimentale Et Clinique, UCLouvain, Brussels, Belgium

    Nathalie Demoulin, Elliott Van Regemorter, Johann Morelle, Valentine Gillion, Nadejda Ranguelov & Nathalie Godefroid

  3. Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium

    Karin Dahan & Charlotte Hougardy

  4. Department of Pediatrics, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Nadejda Ranguelov & Nathalie Godefroid

Authors
  1. Nathalie Demoulin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elliott Van Regemorter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karin Dahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charlotte Hougardy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johann Morelle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valentine Gillion
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nadejda Ranguelov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nathalie Godefroid
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors contributed to the design of the study and review of the manuscript. ND, EVR, and NG wrote the manuscript. JM performed the statistical analysis.

Corresponding author

Correspondence to Nathalie Demoulin.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Graphical Abstract (PPTX 61.6 kb)

Supplementary file2 (DOCX 24 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Demoulin, N., Van Regemorter, E., Dahan, K. et al. Severe parental phenotype associates with hypertension in children with ADPKD. Pediatr Nephrol 38, 2733–2740 (2023). https://doi.org/10.1007/s00467-022-05870-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-022-05870-1

Keywords

Search

Navigation