CAKUT

Title: Outcome and prognostic parameters in children with syndromic and non-syndromic kidney a-/dys-/hypoplasia and CAKUT phenotypes: A pro- & retrospective study collaborating with the European Rare Kidney Disease Registry

Background: Syndromic and isolated congenital anomalies of the kidney and urinary tract (CAKUT) represent the most frequent cause of chronic kidney failure (CKF) in pediatric populations. Among all CAKUT subtypes, kidney dysplasia emerges as the primary contributor to CKF. The ERKNet WG for CAKUT and ciliopathies recently published sonographic consensus criteria for diagnosing kidney hypo- and dysplasia (Kohl et al, NDT, 2022), that have now been integrated into ERKReg. Unlike other established registries for children with CKD and CKF (such as NAPRTC and ESCAPE), ERKReg contains data from >1200 patients with kidney “plasias” including detailed information on the specific sub-phenotype and involvement of either one kidney or both kidneys as well as a very large cohort of patients with multiple syndromic conditions with CAKUT.

• To describe patient characteristics of the ERKReg dysplasia/hypoplasia cohort (age, sex, sonography including application of the suggested sonographic criteria previously published by the ERKNet WG, eGFR courses, genetic diagnoses)
• To describe longitudinal kidney survival in different clinically important sub-groups (for instance dysplasia versus hypoplasia, unilateral versus bilateral involvement, genetic versus non-genetic, syndromic versus non-syndromic, with versus without urinary tract dilatation, dysplasia with LUTO vs dysplasia without LUTO)
• To describe longitudinal kidney survival in patients with specific syndromic CAKUT like BOR syndrome, HDR syndrome, Renal Coloboma syndrome, VACTERL associations, Di George syndrome etc.
• To investigate the dataset for (sonographic) parameters that are associated with better or worse kidney survival and may hold prognostic significance
• To evaluate the ERKReg dataset for clinical plausibility, identify any data inconsistencies or gaps, and determine areas for enhancement in clinical reporting and potential data cleaning needs
• To evaluate the ERKReg dataset for the current application of the ERKNet recommendation (sonographic criteria of dysplasia, clinical follow-up etc.) and a potential clinical significance of re-classification of patients that have not yet been classified according to the ERKNet dysplasia criteria.

This prospective and retrospective study would include patients of all ages who have been diagnosed with renal dysplasia (ORPHA 93108), renal hypoplasia (93101), renal agenesis (411709), oligomeganephronia (2260), congenital megacalycosis (93109), megacystis-megaureter syndrome (238637), fetal lower urinary tract obstruction (435365), medullary sponge kidney (1309), renal tubular dysgenesis (3033), or MCDK (1851).

Additionally, we seek to include all patients exhibiting any CAKUT with relevant CKD (eGFR <60ml/min) (ORPHA group of disorders 93546 AND eGFR filter), based on the hypothesis that conditions of (bilateral) kidney hypo/dys/aplasia may exist in these cases, regardless of their current annotation in ERKReg, which will also be valuable information for a data gap analysis. We will put a focus on the clinical progression of patients with syndromic forms of CAKUT, for which there is a scarcity of data. Consequently, we request datasets on patients with syndromic renal or urinary tract malformations (ORPHA group of disorders 93547).

Data Sources: ERKReg, surveys and HCP centre data

Data Elements:

• Demographic information: Month/Year of birth, sex, ethnicity, date of first presentation to center. Center ID and submitting center’s country.
• Diagnostic survey: Primary renal diagnosis, secondary renal diagnosis, syndromic disorder, further specifications. Date of confirmed diagnosis. Diagnostic methods used to establish diagnosis. Imaging used. Genetic diagnosis and diagnostic methods used to reach diagnosis.
• Sonography information: date of examination, body length, pole-to-pole length, transverse diameter 1 and 2, kidney volume, echogenicity, corticomedullary differentiation, cortical thickness, cysts.
• Annual visit: date, general status (dead/alive/transferred/lost to follow-up), date of change in status. CKD treatment modality (conservative/dialysis/transplantation), date of change in modality. Height, weight, blood pressure, serum creatinine, estimated GFR.

Retrospective registry study primarily utilizing descriptive observational analysis. Kidney survival analysis (Kaplan Meier), log-rank test, regression analyses, ANOVA. If necessary, reach out to ERKNet centers with specific prompts or surveys to gather clinical information crucial for addressing existing data gaps.