Novel imaging techniques for early autosomal dominant polycystic disease

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease caused by genetic mutations in PKD1 or PKD2 and starts already at very early age. Morphologically it is characterized mainly by renal cysts of variable diameter, usually diffusely spread over both kidneys and progressively enlarging in time. This correlates with gradual enlargement of the kidney volume as well as parenchymal destruction, inevitably leading towards end stage kidney disease ( ESKD ). In general, ADPKD progresses slowly and ESKD occurs beyond the fourth decade, also determined by the type of genetic mutation. Increasing number and size of cysts result in increasing kidney volume and is correlated with GFR decline, as demonstrated in the CRISP study. The CRISP study, including adolescents ( > 15 years ) and adults, has also concluded that measuring and summation of the volume of both kidneys on MR, expressed as total kidney volume (TKV), can predict the timing of future renal function worsening. Therefore, TKV is recognized as a prognostic marker for ADPKD disease progression. To include the kidney volume variation with the height of the patient, HtTKV is used. Up to now, there is no cure for the disease but in the last years, therapeutic trials intervening at the level of cyst formation in ADPKD have been initiated in adults to investigate potential stabilization of the disease. The main goal is to preserve kidney function as long as possible by targeting the cyst- and concomitantly TKV growth. Studies have demonstrated that the effect on TKV growth, reflecting the effectiveness of these therapeutic trials, can be measured better early in the disease before severe renal parenchymal destruction and renal function decline. The focus is shifting more and more towards younger age and pediatric population and is becoming the group of interest for different topics of research in ADPKD. I/ Studies investigating the usefulness and evolution of htTKV in children with ADPKD below 15 years of age are not available. Kidney volume can be performed with CT, MR or ultrasound (US), based on 2D ellipsoid volume calculation and/or 3D manual contouring. In the pediatric age group, US is the imaging modality of choice to assess renal volume but practical use and comparison with MR volumetry needs to be further investigated. One of the challenges is evaluating the timeline of htTKV in children with ADPKD with easy accessible two-dimensional US (2DUS) and three-dimensional US (3DUS) and investigate if htTKV at different ages in pediatric ADPKD can predict the evolution of htTKV in adult age. The hypothesis is that age related htTKV assessed with 2D- and 3DUS in pediatric ADPKD can be used for risk stratification to develop renal insufficiency in adulthood. II/ ADPedKD registry (www.ADPedKD.org) is an international multicenter database of clinical, genetical, biochemical and imaging data of pediatric ADPKD until 19 years of age. We have currently more than 1000 patients included. The imaging data will be used to analyse the following questions: - Providing a longitudinal database of US total kidney volume: o Evaluation of the kidney growth in ADPKD compared to matched normal kidney growth o Identification of rapid disease progressors using the kidney growth with 2DUS and / or 3DUS and correlating it with genetical, clinical and biochemical parameters - Evaluating US diagnostic criteria of ADPKD in children and the relation between kidney growth and growth / number of cysts. III/ To assess TKV, accurate renal volumetry is required and can be acquired either with 2D ellipsoid volume calculation either with 3D manual contouring, the “stereology” method. In adults, renal volume is usually assessed with MR or CT. Studies have demonstrated that the stereology method is most accurate to achieve volumes however, in general both methods are accepted.  In order to avoid radiation accompanied with CT or the uncomfort of repeat MR examinations in children, we investigated in a previous study the value of kidney volume measurements with 2DUS ellipsoid method and 3DUS manual contouring in comparison with stereology MR-based volumetry. We found that, after correction with a conversion factor, 3DUS manual contouring volumetry was better comparable with MR volumetry compared to the corrected 2DUS ellipsoid volumetry and a valuable alternative for MR volumetry in children, especially for smaller kidneys. On the other hand, one of the additional findings was that 3DUS manual contouring is a time consuming process and needs more computerized support than 2DUS ellipsoid volumetry. Recently, artificial intelligence is introduced in medicine and network models can be introduced to facilitate clinical decision making and image analysis in several ways, also in renal diseases. We aim to develop a network model to automate acquirement of approved prognostic parameters such as total kidney volume in ADPKD, using ultrasound.