Sickle Cell Nephropathy

To evaluate the diagnostic performance of urinary N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) Biomarkers for detection of early onset of Sickle Cell Nephropathy in children under HU therapy

The goal of this study is to establish whether use of a digital intervention can improve adherence and alignment with the Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease (CKD) 2024 Guidelines. A subset of the study will focus on whether the intervention improves outcomes for young adults living with CKD, in the context of the imminent co-location of Children's Health Ireland on the St. James's Hospital campus. Young adults with CKD transitioning to adult services are recognised as a high-risk and vulnerable cohort, with many individuals unaware of increased cardiovascular risk and mortality¹². In response, and in the context of the co-location of Children's Health Ireland on the St. James's Hospital site, a young adult nephrology clinic has been established. The KDIGO CKD 2024 Guidelines identify transition as a period of increased risk and include recommendations regarding cardiovascular risk factor targets and the use of therapies known to delay CKD progression³. Electronic communication is a preferred method for accessing health information among many young adults⁴⁵ and aligns with Sláintecare digital health strategies⁶. A recently established, award-winning St. James's Hospital renal smartphone application is currently used by over 3,000 individuals living with CKD. The study aims to determine whether use of the application improves adherence to KDIGO guideline recommendations, with the objective of delaying CKD progression and associated complications. The application will support optimisation of care by signposting opportunities for evidence-based interventions (e.g., SGLT2 inhibitors, renin-angiotensin system inhibition) to healthcare providers. The application will also provide participants with tailored recommendations, reminders, educational materials, and collection of patient-reported outcome measures. Due to the diverse population and range of specialties at St. James's Hospital, the young adult clinic serves distinct subgroups, including individuals with sickle cell anaemia and survivors of cancer and haematological malignancies. These populations will be examined in the context of KDIGO guideline implementation, contributing to a limited international evidence base. This research evaluates an intervention designed to improve care for adults living with chronic kidney disease.

Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. These crisis (acute vaso-occlusive crisis) require strong treatment based on morphine, and often require intensive care.However, treatment is often insufficiently effective. Patient can also experiment acute chest syndrome, a complication of vaso-occlusive crisis, which can be responsible for respiratory failure. In addition, patients with sickle cell disease frequently have kidney damage called sickle cell nephropathy, which in the early stages of the disease is responsible for renal hyperfiltration, meaning that the kidneys filter the blood more than necessary, with faster elimination of drugs. For example, it is known that higher doses of antibiotics must be used in these patients than in the general population for the same effectiveness. The hypothesis of the study is that morphine, a drug eliminated by kidneys, is underdosed in patients with sickle cell disease, which is responsible for the difficulties in achieving sufficient analgesia. Objective: To determine the glomerular filtration rate threshold for which it is necessary to prescribe higher doses of morphine in sickle cell patients with vaso-occlusive crisis. Methods: inclusion of 100 patients admitted to intensive care for an acute vaso-occlusive crisis or acute chest syndrome and receiving morphine. Within 24 hours of study inclusion, four morphine dosages will be performed, in parallel with a precise determination of the glomerular filtration rate by measuring the elimination rate of a tracer, 100% eliminated by the kidneys and injected at the start of the study. This tracer is iohexol, a contrast agent commonly used in radiology. Morphine underdosage will be interpretated regarding glomerular filtration rate. The effectiveness of analgesia and the amount of analgesics required will be also be analyzed. Outlook: At the end of this study, the investigators will be able to offer adapted doses of morphine for sickle cell patients in crisis, adapted to glomerular filtration rate, in the aim of personalizing analgesia.

The goal of this National Registry is to is to collect information from patients with rare kidney diseases, so that it that can be used for research. The purpose of this research is to: * Develop Clinical Guidelines for specific rare kidney diseases. These are written recommendations on how to diagnose and treat a medical condition. * Audit treatments and outcomes. An audit makes checks to see if what should be done is being done and asks if it could be done better. * Further the development of future treatments. Participants will be invited to participate on clinical trials and other studies. The registry has the capacity to feedback relevant information to patients and in conjunction with Patient Knows Best (Home - Patients Know Best), allows patients to provide information themselves, including their own reported quality of life and outcome measures.