been a knowledge gap on longitudinal courses of ARPKD and pediatric ADPKD and prognostic markers. Clinically, there is limited published data on severe and rapidly-progressing early-onset ADPKD. For typical ADPKD that progresses to kidney failure at a mean age of 58.1 years for PKD1 patients and at 79.9 years for PKD2 patients frst risk scores have been developed in adult patients [12, 13]. Yet, these scores cannot be fully applied in pediatric and young adult patients as they include age-dependent variables. Height-adjusted total kidney volume (HtTKV) has been associated with hypertension of ADPKD already in children [14, 15], but data on in-depth longitudinal clinical characterization of children sufering from ADPKD remains sparse. Tere is a clear need for evidence-based and targeted treatment in both forms of PKD during childhood and adolescence. ARPKD is a very severe disorder of early childhood. In ADPKD on the other hand cystogenesis starts early in life and kidney function mainly declines once structural changes in the kidney parenchyma are pronounced. It has therefore been suggested that young ADPKD patients could highly proft from early interventions that would retard the development of structural changes in the kidney with subsequent positive longterm efects. Clinical research on ARPKD and pediatric ADPKD has for a long time been hampered by the lack of well-defned primary end points for trials. Most of the current treatment approaches for pediatric PKD therefore remain symptomatic and opinion-based. Te current treatment of severely afected children with ADPKD is based on strict antihypertensive therapy [4, 16]. For treatment of adult ADPKD patients multiple clinical trials are ongoing. Te vasopressin V2-receptor antagonist Tolvaptan has been shown to retard cyst growth and the loss of kidney function in large cohorts of adult ADPKD patients [1]. A clinical trial on the use of Table 1 Comparison of typical clinical features of ARPKD and ADPKD ARPKD OPRHA:731 ADPKD OPRHA:730 Incidence 1:20.000 1:500-1:1000 Main clinical kidney manifestations Prenatal enlarged kidneys, cystic kidneys, oligo-/anhydramnios Chronic kidney disease Hyponatremia Hypertension Increased TKV, cystic kidneys Hypertension Proteinuria Hematuria Chronic kidney disease Kidney Ultrasound Increased echogenicity of kidney parenchyma. „Salt-andpepper“-pattern. Small, sometimes invisible cysts (6 shows a positive predictive value of 90.9% for chronic kidney failure before 60 years of age. Te MayoTKV-Score classifes patients into typical and atypical radiological presentation, with fve age-adjusted htTKV subclasses in the typical group (1A-1E in increasing order). Patients in higher classes show more rapid decline of kidney function and thus have a higher risk to develop CKF after 10 years. For progress in pediatric ADPKD research we will need the association of biobanking and deeply phenotyped patients. The samples obtained during a clinical trial on the efficacy of pravastatin in childhood were for example recently used for metabolic profiling of Liebau and Mekahli Molecular and Cellular Pediatrics (2021) 8:20 Page 5 of 7 children and young adults with ADPKD [29]. An additional recent example in the pediatric field includes the evaluation of plasma copeptin, urinary epidermal growth factor (EGF) and urinary MCP-1 as potential early markers in a cross-sectional study of 53 genotyped ADPKD patients with a mean age of 10.4 years. As expected, kidney function was very good in this cohort with a mean eGFR of 122.7 ml/min/1.73m2 . Patient samples were compared to samples from age-, sex- and BMI-matched healthy controls. While plasma copeptin and urinary EGF did not show major differences, urinary MCP-1 was significantly higher in ADPKD patients compared to controls. This finding was driven by patients with PKD1 variants independent of their underlying genotype. A group of patients with very early onset ADPKD or early symptomatic ADPKD showed higher urinary MCP-1 levels than asymptomatic patients. Human fetal ADPKD kidneys displayed prominent MCP-1 staining and M2 macrophage infiltration and cellular models with PKD1 haploinsufficiency exhibited increased MCP-1 secretion. Thus, urinary MCP-1 may become an easilyobtainable marker of disease severity for subgroups of pediatric ADPKD patients [30]. It may in the future be complemented by radiological findings obtained by both novel MR techniques or 3D-ultrasound [28, 30]. Outlook and Summary Over the past ten years there have been major developments in pediatric PKD research. Te feld has greatly beneftted from the knowledge and the experiences obtained in the general PKD feld and in pediatric nephrology. Tis includes a better understanding of pathomechanisms as well as the identifcation of prognostic markers of disease progression in adult ADPKD patients. A concept is emerging in which ARPKD and ADPKD may be seen as two ends of a disease spectrum with overlapping genetic and clinical features (Figure 1). Te infrastructures generated during the past few years will allow to gain more in-depth insights into the clinical courses of both ARPKD and ADPKD and it appears very likely that clinical risk stratifcation will soon be possible based on the data obtained in the observational studies. Tese data will be supported and complemented by the