clinical variability in both forms of PKD is not well understood and there are also limited prediction markers for disease progression for daily clinical life or surrogate endpoints for clinical trials in ARPKD or early ADPKD. As targeted therapeutic approaches to slow disease progression in PKD are emerging, it is becoming more important to reliably identify patients at risk for rapid progression as they might beneft from early therapy. Over the past years regional, national and international data collections to jointly analyze the clinical courses of PKD patients have been set up. The clinical observations are complemented by genetic studies and biorepositories as well as basic science approaches to elucidate the underlying molecular mechanisms in the PKD feld. These approaches may serve as a basis for the development of novel therapeutic interventions in specifc subgroups of patients. In this article we summarize some of the recent developments in the feld with a focus on kidney involvement in PKD during childhood and adolescence and fndings obtained in pediatric cohorts. Keywords: PKHD1, PKD1, PKD2, Ciliopathies, Genetic Kidney Disease, ARegPKD, ADPedKD © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Introduction Polycystic kidney diseases (PKD) are severe systemic disorders that predominantly afect the kidneys and the liver [1]. Te two main forms of PKD are autosomal recessive PKD (ARPKD; OPRHA:731) and autosomal dominant PKD (ADPKD, OPRHA:730). ARPKD is usually diagnosed prenatally or in the frst year of life. Te disease is characterized by bilateral fbrocystic changes of the kidneys typically presenting with massive organ enlargement due to ubiquitous microcysts mainly developing from the collecting duct. Impairment of kidney function is variable. Antenatal decline of kidney function is associated with oligo-/anhydramnios which subsequently results in pulmonary hypoplasia. Early pulmonary disease in ARPKD is still associated with substantial mortality even in very advanced medical centers. In addition, hepatic involvement due to a developmental defect of bile ducts is an obligatory fnding in ARPKD, which may clinically result in hepatic fbrosis with portal hypertension and bile duct dilatations with an increased risk of cholangitis [1–3]. ADPKD is a more slowly developing disease with clinical symptoms typically becoming prominent in adulthood, even though cyst development starts in childhood or even in utero [1, 4]. Te disease is characterized by progressive development of macrocysts in the kidney developing from all parts of the tubule. Kidney volume Open Access Molecular and Cellular Pediatrics *Correspondence: max.liebau@uk-koeln.de; Djalila.mekahli@uzleuven.be 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 Full list of author information is available at the end of the article Liebau and Mekahli Molecular and Cellular Pediatrics (2021) 8:20 Page 2 of 7 increases with cyst volume. Fibrotic changes in the kidney develop during the course of the disease. Extrarenal manifestations include - amongst others - the development of hepatic cysts, diverticula and hernia, cardiovascular anomalies, and pain (Table 1) [1, 5]. Te genes mainly afected in ARPKD and ADPKD are well-known (PKHD1 (ARPKD), PKD1 and PKD2 (ADPKD)), but the pronounced and poorly understood clinical variability cannot be fully explained by underlying genotypes. Variants in additional genes and frst modifer genes have been identifed [1]. Overlapping phenotypes between ARPKD and rapidly progressing ADPKD, and patients with coincidental variants in multiple PKD genes that show aggravated phenotypes have been described [6]. Biallelic hypomorphic PKD1 variants have been identifed as a common cause of early-onset PKD [7]. In addition to genetic aspects, unknown environmental factors may infuence the phenotype. In this manuscript we focus on kidney involvement in the two main forms of PKD. ARPKD and ADPKD are major contributors to chronic kidney disease (CKD) with ARPKD being an important cause of CKD specially in very young children and ADPKD being the by far most common genetic cause for chronic kidney failure (CKF) in adults. Despite important work by multiple groups [8–11], there has