ongoing cell biological work as well as the power of modern multi-omics approaches to identify early prognostic and predictive biomarkers. For ARPKD the goal will be to achieve promising settings for realizable clinical trials with the two trials mentioned above being a frst major step ahead. For pediatric ADPKD it will be crucial to keep the balance between safety, and tolerability as well as interference in the daily life of children on the one hand and the benefts of early management on the other hand. Here, establishment of easily-obtainable predictive markers of disease progression in childhood Figure 1 Age-dependent changes of the clinical phenotype (light blue), risk factors for rapid disease progression (yellow) and progression of understanding (dark blue) in ARPKD and ADPKD. Overall ARPKD and ADPKD can be seen as two ends of a disease spectrum with overlapping genetic and clinical features Liebau and Mekahli Molecular and Cellular Pediatrics (2021) 8:20 Page 6 of 7 and adolescence as valid primary end points for pediatric clinical trials are urgently needed as a base for the establishment of early targeted treatment. Furthermore, the in-depth clinical characterization of pediatric patients may generate questions for translational research in PKD protein function, thus serving as a stimulus for bidirectional translational research between bench and bedside. Abbreviations ADPKD: Autosomal dominant polycystic kidney disease; ARPKD: Autosomal recessive polycystic kidney disease; CKF: Chronic kidney failure; EGF: Epidermal growth factor; HtTKV: Height-adjusted total kidney volume; PKD: Polycystic kidney disease; PKD1: Polycystic kidney disease 1; PKD2: Polycystic kidney disease 2; PKHD1: Polycystic kidney and hepatic disease 1. Acknowledgement We thank the ESPN Working Groups “CAKUT” and “Inherited Kidney Diseases” for support of the registries, MCL and DM are members of the European Reference Network on Rare Kidney Diseases (ERKNet). – Project ID No 739532. Authors’ Contributions Both authors jointly wrote the manuscript and reviewed the fnal version. The author(s) read and approved the fnal manuscript. Funding Open Access funding enabled and organized by Projekt DEAL. MCL was supported by grants of the German Society for Pediatric Nephrology, the European Society for Paediatric Nephrology (ESPN2014.2), and the Marga and Walter Boll-Foundation. MCL is furthermore supported by the German Federal Ministry of Research and Education (BMBF grant 01GM1903B, NEOCYST consortium) and the German Research Council (DFG Li 2397 5/1). Availability of data and materials Data and material serving as the base for this mini review is available by the authors upon reasonable request. Declarations Ethics approval and consent to participate ARegPKD and ADPedKD were approved by the corresponding ethical committees with the main coordinating centers being Cologne (ARegPKD; Ethics Committee of the Faculty of Medicine of Cologne University) and Leuven (ADPedKD; Ethics Committee of University Hospitals Leuven). Consent for publication Does not apply Competing interests MCL serves on an advisory board of Otsuka Pharmaceuticals as a representative of the University Hospital of Cologne. DM serves on an advisory board of Otsuka Pharmaceuticals, Sanof-Genzyme and Galapagos as a representative of the KU Leuven. The authors have a bias towards their own published data. Author details 1 Department of Pediatrics, Center for Rare Diseases and Center for Molecular Medicine, University Hospital Cologne and Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany. 2 Department of Pediatric Nephrology and Organ Transplantation, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. 3 Department of Development and Regeneration, PKD Research Group, Laboratory of Pediatrics, KU Leuven, Leuven, Belgium. Received: 20 June 2021 Accepted: 22 November 2021 References 1. Bergmann C, Guay-Woodford LM, Harris PC et al (2018) Polycystic kidney disease. Nat Rev Dis Primer 4:50. https://doi.org/10.1038/ s41572-018-0047-y 2. Hartung EA, Guay-Woodford LM (2014) Autosomal Recessive Polycystic Kidney Disease: A Hepatorenal Fibrocystic Disorder With Pleiotropic Efects. Pediatrics 134:e833–e845. https://doi.org/10.1542/peds. 2013-3646 3. Liebau MC (2021) Early clinical management of autosomal recessive polycystic kidney disease. Pediatr Nephrol Berl Ger 36:3561–3570. https:// doi.org/10.1007/s00467-021-04970-8 4. De Rechter S, Bammens B, Schaefer F et al (2018) Unmet needs and challenges for follow-up and treatment of autosomal dominant polycystic kidney disease: the paediatric perspective. Clin Kidney J 11:i14–i26. https://doi.org/10.1093/ckj/sfy088 5. Chebib FT, Torres VE (2018) Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol CJASN 13:1765–1776. https://doi.org/10.2215/CJN.03960318 6. Bergmann C, von Bothmer J, Ortiz Brüchle N et al (2011) Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. J Am Soc Nephrol JASN 22:2047–2056. https://doi.org/10.1681/ ASN.2010101080 7. Durkie M, Chong J, Valluru MK et al (2021) Biallelic inheritance of hypomorphic PKD1 variants is highly prevalent in very