Meckel-Gruber Syndrome

Researchers are studying fetuses with severe kidney failure that causes very low amniotic fluid, a condition called anhydramnios. This lack of fluid can harm lung development and lead to serious health problems or death shortly after birth. The study aims to find out if repeated amnioinfusions, which add fluid to the amniotic sac, can improve survival chances until dialysis or kidney transplant is possible. This research builds on earlier findings and seeks to improve outcomes for families facing this diagnosis. Participants will be divided into two groups: one receiving serial amnioinfusions with routine care, and a control group receiving comfort care without intervention. The amnioinfusions involve injecting sterile fluid into the amniotic cavity using a thin needle guided by ultrasound. The study team will perform these procedures at a specialized fetal care center, adjusting the number of infusions as needed. The trial also includes careful safety monitoring throughout pregnancy and after delivery. During the study, participants will have regular imaging tests like ultrasounds, echocardiograms, and MRIs, along with lab tests to monitor both the fetus and mother. Researchers will track fetal survival to dialysis and transplant, maternal safety up to 30 days after birth, and other pregnancy outcomes such as timing of membrane rupture and delivery. Follow-up will continue until at least two years after birth to assess transplant eligibility and long-term survival.

Researchers are building a comprehensive registry for Hepato-Renal Fibrocystic Diseases (HRFD), which include rare conditions like Autosomal Recessive Polycystic Kidney Disease (ARPKD) and related disorders such as Joubert syndrome and congenital hepatic fibrosis. The goal is to gather clinical and genetic information and create educational resources to help families, doctors, and genetic counselors better understand these diseases. This observational study is designed to support research progress and community awareness through a shared database and biospecimen resources. Participants may choose to contribute to various parts of the study, including a clinical database, genetic testing, tissue donation, and educational resources. Medical records will be reviewed, with data entered into a secure database after removing personal identifiers. Blood or saliva samples may be collected from patients and their parents for genetic analysis, with samples stored at a specialized biorepository. Tissue samples from procedures like nephrectomy or autopsy may also be collected and stored for research. Participants will provide access to their medical information without needing to visit the study center. Data collection includes past, current, and future medical records, with annual updates for ongoing participation. Genetic and tissue samples will be stored and used to support research. The study team monitors the development of this resource over five years to enhance knowledge and treatment options for HRFD. Participation duration varies depending on continued involvement and consent.

Researchers are collecting information from patients with rare kidney diseases to support research and improve care. This National Registry of Rare Kidney Diseases (RaDaR) aims to develop clinical guidelines, audit treatments and outcomes, and help develop future therapies by gathering comprehensive data. Rare kidney diseases often have genetic causes and affect patients from childhood into adulthood, but their rarity makes research and treatment development challenging. The registry gathers clinical data and biological samples from various rare kidney disease groups, each focusing on conditions like Alport Syndrome, APRT Deficiency, Polycystic Kidney Disease, and many others. It connects patients and clinicians and allows patients to contribute information about their quality of life. This infrastructure enables identification of patient groups for clinical trials, biomarker development, and genotype-phenotype studies. Participants provide clinical and disease-specific information over time, which supports epidemiological and translational research. The registry facilitates patient recruitment for studies, improves patient and clinician education, and provides access to current knowledge about rare kidney diseases. The registry is ongoing and primarily includes UK patients but also accepts international participants consented through UK NHS hospitals.

Nephronophthisis (NPH) is a genetic kidney disease caused by mutations in over 20 genes, including NPHP1 and NPHP4. It leads to reduced urine concentration, chronic kidney inflammation, and often progresses to end-stage kidney failure before age 20. NPH can occur alone or with other symptoms like retinal problems and skeletal abnormalities, all linked to ciliary dysfunction. Currently, there is no effective treatment available for this condition. Researchers are studying the proteins and signaling pathways affected by NPHP gene mutations to find new treatment targets. The study collects blood and urine samples from affected patients, healthy relatives, and control groups to analyze urine components through advanced methods like proteome and metabolomics profiling. This helps identify biomarkers and assess drug responses in kidney cells derived from patients. Participants provide samples for multiomics analyses, including protein and microRNA profiling from urine extracellular vesicles. Researchers will monitor these biomarkers to evaluate potential therapeutic targets in urine-derived kidney cells over three years. The main goal is to confirm new targets and support the development of treatments for NPH and related kidney ciliopathies.

Researchers are examining how various maternal lifestyle and environmental factors such as smoking, alcohol use, drug abuse, prescription medicines, and exposure to chemicals can affect human fetal development. The study focuses on fetuses between 7 and 20 weeks of gestation, a critical period for development, to better understand the mechanisms by which these exposures may cause long-term health issues like obesity, hypertension, metabolic syndrome, and infertility. This observational study aims to provide fundamental knowledge about normal fetal development and how adverse maternal influences can alter it, ultimately affecting health in adulthood. The study involves collecting multiple fetal organs and body fluids from normal pregnancies as well as pregnancies where the mother experiences challenges such as smoking, obesity, or exposure to pollutants. Researchers will use various laboratory and microscopic techniques to analyze hormones, genes, proteins, chemicals, and DNA from fetal tissues. The investigation covers many systems including the endocrine, reproductive, nervous, metabolic, cardiovascular, immune, musculoskeletal, and placental development. There is also a focus on maternal emotional health and its impact on the fetus, as well as a study on nerve repair potential. No active intervention is performed; this is a detailed observational research program. Participants will be involved during early pregnancy, with fetal tissue collection occurring between 7 and 20 weeks of gestation. Researchers will gather extensive data on fetal development and maternal lifestyle, including questionnaires related to alcohol use and emotional wellbeing. The main outcome is the creation of a large dataset describing normal fetal development and the effects of maternal environment, which will be used for future research to improve health outcomes. The study includes long-term follow-up of up to 10 years to assess how early fetal exposures relate to adult health and disease risks.